___________________

¹ This workshop was organized by an independent planning committee whose role was limited to identification of topics and speakers. This Proceedings of a Workshop was prepared by the rapporteurs as a factual summary of the presentations and discussions that took place at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants and are not endorsed or verified by the National Academies of Sciences, Engineering, and Medicine, and they should not be construed as reflecting any group consensus.

of the University of Illinois, Urbana-Champaign, Hedvig Hricak of Memorial Sloan Kettering (MSK) Cancer Center, and Roderic Pettigrew of Texas A&M University, emphasized that convergence could develop novel concepts and approaches that can translate scientific and technological advances into meaningful benefits to reduce the burden of cancer and improve care and outcomes. Hricak said that cancer engineering has the potential to revolutionize cancer care in the very near future. Pettigrew added that convergence holds the key to understanding the laws of nature, how they operate, and the most efficient and effective solutions to many health challenges. Bhargava said that cancer engineering could bring the benefits of basic science and technology together to improve lives of those who have experienced cancer. He noted that a major goal of the workshop was to discuss strategies to establish and advance cancer engineering as a discipline, including education and training pathways, to catalyze cancer engineering development and devise the solutions needed to address the complexity of cancer research and care.

This Proceedings of a Workshop summarizes the presentations and discussions. Observations from individual participants on the current state and

a shared commitment across the academies to tackle one of humanity’s most persistent and devastating health challenges.

John Anderson, president of NAE, said that it is essential for cancer control to be viewed as a complex adaptive system that spans prevention, diagnosis, treatment, and survivorship and sits at the intersection of policy, infrastructure, and human behavior. Anderson highlighted the need for a systems engineering approach to cancer control, which considers both system components and connections. He said that engineering is building resilient and purposeful systems and systems engineering offers a map, mindset, and method. Anderson added that educating and training the next generation of cancer professionals across disciplines (e.g., biology, policy, systems engineering) is also part of a systems-oriented national cancer strategy.

Several participants shared their perspectives on convergence and the importance of cancer engineering for advancing cancer care.

The Power of Convergence in Transforming Cancer Care

Phillip Sharp from the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT), who was one of the first to establish the concept of convergence, provided a keynote presentation in which he described it as the “third revolution” in biomedical research, following the molecular biology and genomics revolutions (NRC, 2009; Sharp et al., 2011). Sharp said that in 2011, MIT established the Koch Institute for Integrative Cancer Research with eight engineers and eight cancer biologists to jointly leverage advances in engineering to advance cancer research. He noted that similar convergence efforts were also underway at other institutions.

Sharp described several examples of the application of convergence. He said that after sequencing the human genome and identifying mutations associated with some cancers, computational tools and AI are now being applied to develop precision treatments (e.g., deriving protein structures from the genetic sequence to identify new therapeutic targets and design drugs that target specific altered proteins.) As an example, Sharp said, 20 years ago, anaplastic lymphoma kinase (ALK)–positive non-small-cell lung cancer⁴ had a 5-year survival rate of 2 percent. Now, precision treatments have raised that to 50 percent (Mok et al., 2020). He noted that while this is a significant advance, it is not a cure, and patients often relapse as resistance to targeted

___________________

⁴ A cancer is ALK positive if the ALK gene, which aids in digestive and nervous system development, has been activated and fused to another gene, which can cause cancer. These cancers make up 4 percent of all lung cancer diagnoses and are often found in non-small-cell lung cancer. See https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/alk-lung-cancer (accessed August 5, 2025).

treatments develops, because “precision medicine is in competition with the instability of cancer.”

Convergence also has a role in the development of immunologic treatments for cancer, which depend on antigen identification, immune cell recognition, cellular interactions, and signals controlling immune responses, Sharp said. He noted that immunotherapies for advanced melanoma, for example, have improved 10-year survival to 50 percent (Wolchok et al., 2024).

Sharp said that convergence is also critical in the interception of cancer, which is identifying and treating very early-stage cancer or pre-malignant lesions. He pointed out that one element of interception is predicting future cancer risk. Sharp described the work of Regina Barzilay at MIT on the application of machine learning to predict future risk of breast cancer from breast imaging (Yala et al., 2019). He added that this approach is being validated around the world so that training the model is equally effective for different populations. Another approach involves early detection of molecular markers of cancer in the blood (e.g., tumor DNA), and Sharp mentioned the work of Sangeeta Bhatia at MIT on improving the sensitivity of this type of assay. “Understanding the risk of development of cancer in a more quantitative, reproducible way gives us the possibility of having better control of the disease process,” he said.

In the face of rising U.S. health care costs, Sharp said that one goal of engineering and convergence in cancer is designing systems that more effectively deliver care to patients. Effective interception will require value-based evaluation of innovations (e.g., costs, outcomes, patient well-being) and access to health care, including emerging technologies, patient education, and patient support. As an example, he said that federal law requires notifying patients whose imaging shows dense breast tissue, which could suggest a need for additional monitoring.⁵ However, studies by Barzilay suggest that 40 percent of those with dense breast tissue are not at increased risk of cancer. Sharp added that the challenge is assessing the value of this information to patients, balancing the value of knowing about a potential future risk of cancer with anxiety or excess monitoring for those who might not actually be at increased risk.

___________________

⁵ 42 USC 263b: Certification of mammography facilities, see https://www.govinfo.gov/app/details/USCODE-2008-title42/USCODE-2008-title42-chap6A-subchapII-partF-subpart3-sec263b (accessed August 22, 2025).

___________________

⁶ For background, Bashir referred participants to a 2016 report by Sharp and colleagues (Convergence: The Future of Health, https://static1.squarespace.com/static/632c9df5490c364ddc05461c/t/66354e9aa5c83960782480c5/1714769562530/Convergence-The-Future-of-Health-2016-Report.pdf (accessed August 4, 2025), an associated publication that he said “laid the foundation” for convergence (Sharp and

on translating laws of physics and chemistry into forward design, which distinguishes it from the sciences, which are more discovery focused.

Bashir said that a challenge for convergence is engineering access to the biomedical domain. He added that the vision of Grainger College of Engineering is “to sustain a healthier planet, to save people’s lives, [and] to help society thrive.” He also noted that the college has developed strategic partnerships with local and national health organizations. Furthermore, the Cancer Center at Illinois was the first cancer center built on the convergence of engineering and oncology and integrates engineering and biological systems with technology and data science.

Bashir also discussed the need for structural transformation of medical education. He proposed a medical curriculum in which innovation, design, entrepreneurship, engineering, data science, and AI are integrated into the biological and clinical science curriculum. Bashir said that this is the approach of the Carle Illinois College of Medicine, the first accredited engineering-based college of medicine, which was launched in 2018.⁷ Bashir emphasized that team science needs to be recognized and rewarded, particularly in the hiring, promotion, and tenure processes.

Convergence of Data Science, AI, and Virtual/Digital Platforms

Cheryl Willman from the Mayo Clinic discussed its mission to “use our unique platforms, digital technologies, AI, and intelligent automation to foster innovative research and transform the delivery of cancer care and clinical trials in clinical, home, and community settings.”

Willman said that the core of the initiative to transform health care is the Mayo Clinic Platform.⁸ In partnership with Google and Microsoft, 14 million longitudinal patient records from all patients 2003–present have been digitized in the cloud component of the platform, she said.⁹ Willman noted the ongoing efforts to integrate clinical notes, diagnoses, laboratory tests, digitized pathology images and reports, and digitized radiographic images. Willman said that another component of the platform is “the world’s largest distributed

___________________

Hockfield, 2017), and a 2015 perspective on the role of engineering in translational medicine (Chien et al., 2015).

⁷ See https://medicine.illinois.edu/about (accessed August 14, 2025).

⁸ See Mayo Clinic Platform, https://www.mayoclinicplatform.org/ (accessed September 25, 2025).

⁹ See Understanding Mayo Clinic Platform: A Strategic Overview for Health IT Leaders, https://www.healthcareittoday.com/2025/06/16/understanding-mayo-clinic-platform-a-strategic-overview-for-health-it-leaders/ (accessed August 14, 2025).

global health care data network,” which enables participating institutions from around the globe to share deidentified clinical data.

Willman discussed the longitudinal and multimodal data in the Mayo Clinic Platform to support cancer research (e.g., AI-driven drug discovery and early cancer detection and interception), clinical trials (e.g., decentralized distributed clinical trials, in silico clinical trials), and clinical practice (e.g., practice automation, agentic AI,¹⁰ personalized care, digital twins,¹¹ and virtual avatars for patient and community education). As one example, Willman described the work of Goenka and colleagues at the Mayo Clinic to develop an “AI-powered, radiomics-based machine learning method capable of detecting visually occult pancreatic cancer in a normal-appearing pancreas on pre-diagnostic computed tomography scans” years before the cancer is detectable clinically (Korfiatis et al., 2023).

Mayo Clinic Platform technology and tools also support the Cancer Care Beyond Walls program,¹² which allows some patients to receive outpatient care, chemotherapy, and supportive care at home (e.g., via telehealth, remote monitoring, and collaboration with community-based allied health care teams) (Dronca et al., 2025). Willman noted that this approach could increase access to treatment, reduce patient financial burden, and promote health equity.

Similarly, the Clinical Trials Beyond Walls program leverages Mayo Clinic Platform digital tools to enable decentralized cancer clinical trials. The capabilities can include video consent, video visits, medication delivery, remote bio-specimen collection, and remote participant monitoring via a range of devices. Willman said that the program includes more than 2,500 Mayo Clinic trials, including 680 that are entirely decentralized. She highlighted an example of a home-based cancer care delivery trial aimed at reducing disparities in prostate cancer outcomes in the United States and sites in Africa, particularly for Black men, who are often unable to pursue treatment at a health care facility.¹³

The Mayo Clinic is considering what the full arc of cancer care will look like, from risk assessment through survivorship, Willman said. This includes studying how best to leverage data, digital tools, and technologies to transform cancer diagnostics, care delivery, and clinical trials and improve patient experi-

___________________

¹⁰ Agentic AI focuses on proactive systems that can autonomously perform tasks and make decisions rather than answer prompts, as generative AI does.

¹¹ In health care, a digital twin is a data-driven, dynamic replica of a biological system, which can be analyzed and further personalized medicine.

¹² See Mayo Clinical Trials and the Clinical Trials Beyond Walls program, https://www.mayoclinic.org/giving-to-mayo-clinic/our-priorities/ct (accessed August 14, 2025).

¹³ See A Study to Reduce Disparities in High-Risk Black Men (BM) With Advanced Prostate Cancer Using Patient-Centered Home Care, https://www.mayo.edu/research/clinical-trials/cls-20536300 (accessed August 22, 2025).

ence and outcomes. Willman observed that new technology has often been developed without a clear application, but an emerging synergy of clinicians and health care leaders is defining questions that require a computational or engineering solution.

Federal Support for Convergence of Engineering and Health

Bruce Tromberg from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) at the National Institutes of Health (NIH) discussed how NIH is supporting the advancement of cancer engineering. NIBIB was established in 2000 by Public Law 106-580 to conduct basic research in imaging, bioengineering, computer science, informatics, and related fields. It accounts for only about 1 percent of the total NIH budget but has been highly influential in establishing bioengineering across all 27 NIH institutes and centers, Tromberg said. For 2023, nearly 14 percent of the total NIH budget was dedicated to bioengineering (about $7 billion). This is a 139 percent increase over 2008 spending on bioengineering, and Tromberg pointed out that the total NIH budget increased 61 percent over the same period. Unlike other NIH institutes, all NIBIB program officers are engineers and physical scientists.

“Cancer engineering is the number one application focus across NIH,” Tromberg said. NIH investment in cancer engineering for 2024 was around $900 million, with NIBIB accounting for around $79 million. For Fiscal Year 2020–2024, National Cancer Institute (NCI) spending for cancer engineering was more than $3 billion (about 9 percent of the total NCI appropriated budget).

NIBIB funds about 900 grants per year across five main areas: therapeutic systems; engineered biological systems; sensors and point-of-care technologies; imaging technologies; and data science, modeling, and computation. Tromberg noted that most funded grants integrate several of these areas, and a biological hypothesis is not a requirement for funding.

Since the creation of NIBIB, U.S. biomedical engineering programs have been steadily increasing, and Tromberg noted the more than 200 graduate programs. Human health is now a top priority in engineering, he said, and NIBIB support has driven numerous medicine–engineering partnerships and unprecedented levels of innovation and entrepreneurship all around the country.

Looking to the future, Tromberg noted many areas for engineering–medicine partnerships (e.g., biomanufacturing, quantum technologies). One key opportunity for cancer engineering is developing the precision diagnostics to realize the promise of precision medicine and personalized therapies. There is also a focus on developing technologies that can reduce costs and increase patient access.

___________________

¹⁴ See https://standuptocancer.org/ (accessed August 15, 2025).

¹⁵ See SU2C Our Story, https://standuptocancer.org/who-we-are/our-story/ (accessed September 11, 2025).

¹⁶ These proteins help repair single-strand breaks in DNA. Inhibiting them causes double-strand breaks that tumor cells cannot repair, leading to cancer cell death. See https://www.cancer.gov/publications/dictionaries/cancer-terms/def/parp-inhibitor (accessed August 15, 2025).

¹⁷ PD-1 is a T cell protein that tempers the immune system when bound to PD-L1. Inhibiting or blocking PD-1 increases the immune system’s ability to target and kill cancer cells. See https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors (accessed August 16, 2025).

sets from liquid biopsies” (e.g., blood, urine, saliva, exhaled volatile organic compounds).¹⁸

Adams said that SU2C has special convergence teams to develop new cancer vaccine platforms,¹⁹ including a messenger RNA (mRNA) vaccine for pancreatic cancer (discussed later by Balachandran and Cooke). He added that SU2C teams are also focusing on understanding why some cancer diagnoses, including colorectal, stomach, breast, and pancreatic, are increasing among individuals aged 15–50.

Capturing Circulating Tumor Cells

Mehmet Toner from Massachusetts General Hospital and Harvard Medical School discussed technological advancements in circulating tumor cells (CTCs) capture and implications for early cancer detection. Toner said that more than 30 trillion cells, including cancer cells, are circulating in an individual’s blood at any given time, and an analysis of CTCs could be useful for monitoring disease progression, individualized drug testing, and potential early detection of cancer.²⁰ However, CTCs are rare, and detection is technologically complex, he said. Toner said that a noninvasive liquid biopsy would need to be able to sample a large volume of blood but could be a “robust, high-throughput, clinical-grade device.” To facilitate the convergence to achieve this, Toner explained how he and a colleague effectively combined their “intellectual and funding resources” and merged their laboratories at Massachusetts General Hospital

Toner said that early work focused on developing a “CTC-Chip,” a microfluidic platform to screen every cell in a large-volume blood sample (Nagrath et al., 2007). He said that the high-throughput system has the capacity to identify one cell in 200 billion cells and can analyze a liter of blood that has 5 trillion cells within an hour. Cells remain viable and can be isolated for further analyses. A challenge for applying this approach as an early diagnostic is the large volume of blood needed to ensure the collection of a sufficient number of rare CTCs.

Toner described how leukapheresis is now being used with an advanced CTC-Chip to harvest potentially cancerous cells from a patient’s full blood volume. The blood is first passed through a chip that removes red blood cells

___________________

¹⁸ See SU2C Innovation Summit: AI in Cancer Research, Diagnosis, and Treatment, https://standuptocancer.org/wp-content/uploads/FINAL-REPORT-2024-SU2C-Innovation-Summit-AI-in-Cancer-Research-Diagnosis-Treatment.pdf (accessed September 11, 2025).

¹⁹ See SU2C Convergence, https://standuptocancer.org/what-we-do/scientific-initiatives/ (accessed August15, 2025).

²⁰ CTCs are shed by a primary tumor and leak into the bloodstream.

and platelets. The remainder is processed through a second chip that removes white blood cells, leaving nucleated cells that are enriched for tumor cells (Mishra et al., 2025). Toner noted that clinical results from testing entire blood volumes of patients with prostate, breast, liver, and melanoma tumor types found that it can effectively isolate thousands of viable cancer cells. These cells can be used to determine tumor tissue of origin and gene copy number variation, as well as whole exome sequencing and single-cell RNA sequencing for further characterization. Efforts are underway to combine this process into a single chip, which Toner said could be low-cost, disposable, and rapid, and would incorporate an automated cell separation technology.

Personalized mRNA Cancer Vaccines

John Cooke from Houston Methodist Research Institute discussed how the convergence of engineering with RNA innovation is shaping the future of drug development and distribution. Cooke listed two types of mRNA cancer vaccines, those targeting neoantigens that are shared by tumors (and can therefore be off-the-shelf products) and personalized vaccines encoding neoantigens specific to a patient’s tumor. He described examples of early success with the latter, including the vaccines for pancreatic cancer (discussed by Balachandran next).

The personalized mRNA cancer vaccine program at Houston Methodist is launching a clinical trial for a personalized vaccine against triple-negative breast cancer (Chervo et al., 2024). The process starts with patient identification, tumor sampling, and sequencing, so that 20–30 neoantigens can be selected. Then, clinical-grade mRNA encoding these neoantigens is synthesized according to a design predicted to enhance stability and functionality (Sethna et al., 2025). Antigen design is the critical process, Cooke said, which involves AI and machine learning–assisted computational identification, prioritization, and optimization of neoantigens most likely to be immunogenic. It also includes adding signal sequences that facilitate cytoplasmic processing and presentation of the antigens on the cell surface. The mRNA is validated, encapsulated in clinical-grade lipid nanoparticles, and validated again, and the finished vaccine is provided to the investigational pharmacy for immunization of the trial participant.

Cooke noted that deployable manufacturing units are currently being developed to support manufacturing mRNA vaccines in low- and middle-income countries and producing medical countermeasures for public health emergencies. He suggested that academic hospitals could use them to produce vaccines that meet the standards of Good Manufacturing Practice for clinical trials and therapy in hospital-based programs. Cooke observed that in the future, a network approach could entail a central facility receiving tumor

samples from regional and outlying hospitals, sequencing, and sending personalized vaccines to regional hospitals or DNA templates to outlying hospitals for use in deployable manufacturing units.

Cooke pointed out that challenges of developing mRNA vaccines include the lack of uniformity across the algorithms used to design the neoantigen amino acid sequences and the need to learn about the different forms of eligible mRNA. Providing personalized cancer vaccines at the point of care also faces manufacturing, quality control, regulatory, and systems issues.

However, “the limitless potential of RNA therapeutics combined with manufacturing advances will enable hospital-based personalized precision medicine that is affordable and accessible,” Cooke said, and the technology of mRNA cancer vaccines combined with deployable manufacturing units will facilitate hospital-based, point-of-care treatment.

mRNA Vaccines for Pancreatic Cancer

Vinod Balachandran from MSK Cancer Center said that a fundamental challenge for cancer vaccines has been how to teach the immune system to recognize cancer. A cancer vaccine has to induce strong, specific, functional, and durable T cells in the patient, which calls for the convergence of science, medicine, and engineering.

Balachandran described work at the Olayan Center for Cancer Vaccines to develop a vaccine for pancreatic ductal adenocarcinoma (PDAC), which is the most common and highly lethal form. He said that PDAC has been described as “immunologically invisible” because it has a low mutation rate, resulting in few neoantigens.²¹ This leads to limited T cell infiltration and makes PDAC generally insensitive to immunotherapy. However, an association has been found between long-term survival in some patients and PDACs expressing somatic passenger neoantigens that elicit natural T cell immunity. Based on this finding, Balachandran and colleagues set out to study whether delivery of a personalized RNA neoantigen vaccine to patients with PDAC could elicit sufficient neoantigen-specific T cells to delay recurrence.

Balachandran discussed the results of an investigator-initiated Phase 1 clinical trial in patients with PDAC, which showed proliferation of neoantigen-specific T cells after vaccination (Sethna et al., 2025). He said that further analyses confirmed that the T cell response was specific to vaccine antigens (rather than a nonspecific response to the RNA component); it was durable, with the life-span of T cell clones estimated to be more than 10 years after

___________________

²¹ A neoantigen is “a new protein that forms on cancer cells when certain mutations occur in tumor DNA.” See https://www.cancer.gov/publications/dictionaries/cancer-terms/def/neoantigen (accessed August 18, 2025).

priming and single booster vaccines; and the personalized vaccines induced robust and durable T cell responses in 50 percent of patients. Extended followup of more than 3 years shows that vaccine responders have a prolonged median recurrence-free survival (versus median recurrence-free survival of vaccine non-responders of 13.4 months). Acknowledging that this was a small trial, and “correlation does not imply causation,” Balachandran said that the findings support the further investigation of cancer vaccines as a promising immunotherapy across a range of cancers. He added that a global Phase 2 randomized controlled trial is underway.

Opportunistic AI for Predicting Cancer Outcomes

Anant Madabhushi from Emory University discussed the role of AI and computational imaging in developing improved tools for diagnosis and prediction of disease outcomes, progression, and treatment response that will support precision medicine. One of the key concerns in medicine is the lack of transparency of AI decision making (the “black box” aspect). There are also concerns about algorithm reproducibility (e.g., a model trained at one site is not necessarily generalizable to other sites), and the potential for hallucination by large language models (where models provide compelling but inaccurate or false responses to questions).

As an example of the potential of AI, Madabhushi showed the ability to extract increasingly detailed information from a chest CT scan of a patient with lung adenocarcinoma (e.g., tumor-associated vasculature, intra- and peri-tumoral texture)²² and digitized slides of a resected tumor (e.g., single cell identification, mapping of tumor features), which can be linked to outcomes and used for predicting treatment response.

Madabhushi highlighted several other examples of his work with AI tools to advance cancer care. He said that a challenge in breast cancer treatment has been predicting which patients with early-stage estrogen receptor–positive cancers²³ will benefit from chemotherapy and which are at low enough risk to forgo it. The Oncotype DX genomic assay²⁴ has been used to determine patient risk of recurrence and probability of benefit from chemotherapy.

___________________

²² This is a non-small-cell lung cancer and the most common type of lung cancer. See https://www.ncbi.nlm.nih.gov/books/NBK519578/ (accessed August 18, 2025).

²³ Estrogen receptor–positive breast cancer cells have a protein that binds to estrogen. These cells may need estrogen to grow, so they are often treated with estrogen-blocking treatments. See https://www.cancer.gov/publications/dictionaries/cancer-terms/def/estrogen-receptor-positive (accessed August 18, 2025).

²⁴ See Oncotype DX: About the test, https://www.oncotypedxtest.com/en-ie/healthcare-professionals/what-is-the-oncotype-dx-test (accessed August 18, 2025).

Madabhushi explained that this method is “a tissue-destructive assay that costs approximately $4,000 per patient.” His research group is investigating the opportunistic application of AI to predict chemotherapy benefit using routinely acquired clinical data. Specifically, they are leveraging machine learning to assess the degree of disorder of collagen fibers in tumor-associated stroma on tissue stained with hematoxylin and eosin (H&E). He said this approach showed that patients with short-term survival had very structured collagen, while highly disordered collagen was associated with long-term survival. This association has been validated in a clinical study (Li et al., 2021). Using a similar AI approach, it was shown that the extent of immune infiltration seen on H&E slides from patients with ductal carcinoma in situ²⁵ could be used to predict risk of recurrence and benefit from radiation therapy (Li et al., 2024).

Other examples Madabhushi discussed included an opportunistic AI approach to identify a biomarker in H&E slides to predict benefit of docetaxel²⁶ treatment of patients with metastatic castration-sensitive prostate cancer²⁷ and AI-based virtual staining to identify prognostic markers in H&E slides. Madabhushi said that AI is also being studied to identify biomarkers in retinal images that could predict risk of onset of hematologic malignancies²⁸ a decade before diagnosis.

“AI is not magic. One has to be thoughtful and intentional in developing these algorithms,” Madabhushi cautioned. He suggested that low-cost computational approaches to diagnostics can promote health equity and could be particularly important for low- and middle-income countries. He also cautioned that there is a “critical need to validate [opportunistic AI approaches] on completed and prospective clinical trials to establish predictive validity and establish higher levels of evidence.”

The issue of the environmental impact of deploying technologies was raised during the discussion, such as the energy consumption associated with

___________________

²⁵ This is “a condition in which abnormal cells are found in the lining of a breast duct. The abnormal cells have not spread outside the duct to other tissues in the breast. In some cases, ductal carcinoma in situ may become invasive breast cancer and spread to other tissues.” See https://www.cancer.gov/publications/dictionaries/cancer-terms/def/ductal-carcinoma-in-situ (accessed August 18, 2025).

²⁶ “Docetaxel is a type of chemotherapy called a ‘taxane.’ Taxanes interfere with microtubules (cellular structures that help move chromosomes during mitosis). It blocks cell growth by stopping mitosis (cell division).” See https://www.cancer.gov/about-cancer/treatment/drugs/docetaxel (accessed August 18, 2025).

²⁷ Castration-sensitive cancer does not respond to treatments that lower testosterone. See https://www.cancer.gov/about-cancer/treatment/drugs/docetaxel (accessed August 18, 2025).

²⁸ Hematologic malignancies are “cancer[s] that begins in blood-forming tissue, such as the bone marrow, or in the cells of the immune system.” See https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hematologic-cancer (accessed August 18, 2025).

manufacturing chips, implementing AI models at scale, or distributing vaccines. Madabhushi said it is important to be pragmatic when deploying AI-based tools in low- and middle-income countries and low-resource settings. Consideration should be given to the sustainability of a technology model regarding power consumption and carbon footprint, for example, lest it be undeployable in some settings, he said.

Systems Engineering to Improve Early Cancer Detection and Prevention in Low-Resource Settings

Rebecca Richards-Kortum from Rice University said that cancer is the second-leading cause of death in the United States, and a disproportionate burden of cancer affects medically underserved populations and racial and ethnic minorities.²⁹ Richards-Kortum stressed that early cancer detection can save lives and improve outcomes at lower cost.³⁰ She said that despite the availability of early detection tests, less than half of patients are diagnosed at an early stage when cancer is still localized (Hong and Ding, 2025; Steuer et al., 2015).

Richards-Kortum highlighted the need for a systems engineering approach to ensure that cancer prevention and early detection technologies reach patients. She said that technology development needs to occur in an ecosystem that includes not only health care systems but also patients, researchers, manufacturers, regulatory agencies, distributors, and the government. A systems approach integrates it with policy development and implementation science.

There are also lessons to be learned from the global health community, she said, and referred participants to the World Health Organization global strategy to eliminate cervical cancer, which established clear targets.³¹ Some U.S. states are taking action, and she noted that Alabama has launched an innovative strategic plan to eliminate cervical cancer in the state.³²

“We need health care providers that know how to implement cervical cancer prevention strategies, from vaccination, to screening, to diagnosis, to treatment of pre-invasive disease,” Richards-Kortum said, and she described

___________________

²⁹ For more information on cancer disparities, see https://www.cancer.gov/about-cancer/understanding/disparities (accessed August 19, 2025).

³⁰ See https://www.who.int/activities/promoting-cancer-early-diagnosis (accessed August 19, 2025).

³¹ See https://www.who.int/initiatives/cervical-cancer-elimination-initiative (accessed August 19, 2025).

³² See https://www.alabamapublichealth.gov/bandc/assets/cervicalcancer_actionplan.pdf (accessed August 19, 2025).

several examples of how technologies can help. One example was a low-cost, anatomically correct set of gel-based cervical models built by Rice University and students from Malawi Polytechnic to train clinicians on how to do biopsies.³³ She noted that these are in use by some colleagues at MD Anderson to train clinicians in rural and remote areas around the world. Another example is MD Anderson’s Project ECHO, which provides telementoring to improve clinician cancer care skills in 27 countries.³⁴ There are also point-of-care tools, such as a rapid test for detection of HPV DNA (Kundrod et al., 2023). Another example is a $500 pocket colposcope, which incorporates AI-based analysis to support point-of-care diagnosis of cervical pre-cancer (Skerrett et al., 2022). Richards-Kortum is also working on point-of-care pathology systems, including an affordable AI-enabled microscopy platform (Jin et al., 2020, 2024).

Richards-Kortum called for applying a system lens to identifying priority areas for the development of early detection technologies and said that global collaborations can speed up development and evaluation. She added that technology development should be a core part of public health efforts to improve cancer prevention and early detection.

Christina Chapman, Baylor College of Medicine, further emphasized the importance of systematically leveraging strategies employed in both domestic and international low-resource settings. In addition, she highlighted the value of conducting research in less traditional environments. As an example, she mentioned a groundbreaking study done in the 1980s by the U.S. Department of Veterans Affairs (VA) on alternatives to laryngectomy for laryngeal cancer (Spaulding et al., 1994). She described this as “an example of a trial that really could have only existed in the VA setting because of the way that insurance is structured” and said that achieving sufficient participant accrual would likely not have been possible in traditional academic research settings.

FROM CANCER BIOLOGY TO ENGINEERING SOLUTIONS

Several participants discussed examples of transformative engineering approaches and cutting-edge technologies and developments stemming from the convergence of engineering and cancer biology and how some of these technologies could accelerate cancer research and improve outcomes for individuals with cancer.

___________________

³³ See https://news2.rice.edu/2018/04/16/rice-u-students-create-training-device-for-cervical-cancer-screening-2/ (accessed August 21, 2025).

³⁴ See https://www.mdanderson.org/education-training/outreach-programs/project-echo.html (accessed August 21, 2025).

later). He discussed a clinical trial of personalized cancer vaccines for advanced melanoma, which showed a 44 percent reduced risk of recurrence or death at 2 years and 49 percent at 3 years (Weber et al., 2024). He provided data on how the vaccine can be encapsulated in microparticles of a polymer, poly (lactic-coglycolic acid), which are designed to degrade at specific times (McHugh et al., 2017). Finally, Langer said that research is underway to develop microneedle patches for vaccination and portable 3-D printers for their production that could expand access. Langer added that it is essential to reach out to regulatory agencies for advice at the early stage of conceptualizing an innovative technology.

Engineering for CAR T Cell Therapy

Carl June from the University of Pennsylvania Perelman School of Medicine discussed the development of CAR T cell therapy, noting that the idea of therapeutic genetic manipulation of cells was first proposed in the early 1970s, around when molecular cloning was first accomplished (Friedmann and Roblin, 1972). The first such therapy was approved by the U.S. Food and Drug Administration (FDA) in 2017 (Maude et al., 2018). June said that all seven FDA-approved CAR T cell therapies are autologous,³⁵ but research is ongoing to develop allogeneic, or “off-the-shelf,” CAR T cells from sources such as cord blood, healthy donors, or induced pluripotent stem cells.

June explained that the development of CAR T cell therapy required a combination of three different technologies: CAR technology that facilitates T cell binding to an antigen, independent of the major histocompatibility complex; adoptive cell therapy, which developed methods for culturing patient T cells for reinfusion; and gene therapy, which developed methodologies to genetically modify cells. He described developing the first CAR T cells for patient infusion in 2010, which were autologous T cells from patients with refractory leukemia, modified to target CD19 (a B cell antigen). He shared updates on two patients who remain cancer free: a man who was the second patient treated in 2010 and a young woman who was 7 years old when she was treated in 2012. June said that both still have circulating CAR T cells expressing CD19. June explained that antigen selection is a challenge because T cells can also target normal cells, which he referred to as on-target but off-tumor recognition. He noted that more than 50,000 patients worldwide have been treated for hematologic malignancies. However, given rare cases of T-cell

___________________

³⁵ Autologous CAR T cells are created by harvesting the patient’s own T cells, genetically reprogramming them, and reinfusing them in the original patient.

malignant transformation with autologous CAR T cells, FDA has required a warning be added to the product label for all such therapies.³⁶

When engineering T cells, details matter, June said. He described a study of the feasibility of using a type of gene editing called “clustered regularly interspaced short palindromic repeats” (CRISPR)-Cas9³⁷ for the preparation of autologous T cells. When comparing his findings with those of Jennifer Doudna’s laboratory (Doudna and Charpentier, 2014),³⁸ it was discovered that their different approaches to preparing T cells before gene editing (resting versus activated cells) resulted in different levels of chromosome loss downstream of the edited gene in the cells. June said that his lab and others are now studying adenine base editing³⁹ as an alternative to CRISPR-Cas9 gene editing, and they have found that this method results in healthier CAR T cells (Engel et al., 2025).

June emphasized the importance of effective collaboration and said that CAR T cell therapies are now being studied to treat solid cancers, as well as for other conditions, such as heart failure and fibrosis, human immunodeficiency virus, and autoimmune diseases. He noted that several clinical trials of CAR T cell therapies for cancer are also underway worldwide.

June said there might also be opportunities to develop vaccines that prevent tumors in individuals who are genetically predisposed to a cancer. However, the timeline to complete a clinical trial for the development of such vaccines would be impractically long.

Engineering Natural Killer (NK) Cells for Cancer Treatment

Katy Rezvani from the University of Texas MD Anderson Cancer Center shared findings from her work on developing allogeneic CAR NK–cell therapies. Rezvani said that as part of the innate immune system, NK cells have multiple germline-encoded surface receptors that allow them to recognize abnormal cells (e.g., cancer cells, virally infected cells) and kill them. One

___________________

³⁶ See https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed (accessed August 4, 2025).

³⁷ CRISPR-Cas9 is “a laboratory tool used to change or ‘edit’ pieces of a cell’s DNA.” Cas9 is an enzyme used to make cuts in specific sequences of DNA, where other DNA strands can be inserted. See https://www.cancer.gov/publications/dictionaries/cancer-terms/def/crispr-cas9 (accessed August 22, 2025).

³⁸ Jennifer Doudna and Emmanuelle Charpentier are credited with discovering CRISPR-Cas9 technology.

³⁹ Adenine-based gene editing directly converts adenine-thymine base pairs into guanine-cytosine pairs without introducing double-strand breaks in the DNA.

advantage over T cells is that allogeneic administration of NK cells does not cause graft-versus-host disease⁴⁰ (Lundqvist et al., 2007; Olson et al., 2010). She pointed out that while CAR T cells are associated with certain toxicities, these have not been observed with NK cells. A disadvantage, however, is that without cytokine support, the life-span of NK cells is only 1–2 weeks, so supplemental cytokines are necessary. Another challenge is determining the most appropriate donor cells, as they could be used to manufacture hundreds or even thousands of therapeutic doses, she said.

Rezvani described the development of “armored” anti-CD19 CAR NK cells, in which the CAR vector also encoded a gene for a cytokine, interleukin (IL)-15, and a gene for inducible caspase 9, which served as a safety switch. The resulting CAR NK cells were administered to 11 participants with CD-19-positive lymphoid tumors in a Phase 1 clinical trial (Liu et al., 2020). Rezvani reported that seven of the 11 experienced complete remission. Furthermore, these allogeneic, human leukocyte antigen–mismatched cells did not result in any toxicities or graft-versus-host disease, and they were still detectable in peripheral blood samples more than 1 year later. The population was expanded to 37 participants with CD-19-positive lymphoid malignancies for the Phase 2 trial. Rezvani said that at 1 year, the overall and progression-free survival were 68 and 32 percent (Marin et al., 2024). These outcomes are comparable to those achieved with autologous CAR T cells in similarly heavily pre-treated patients. A retrospective analysis to identify the optimal cord blood characteristics for harvesting NK cells found that better overall survival and 1-year progression-free survival were associated with NK cells manufactured from umbilical cord blood units frozen within 24 hours of collection and with a low nucleated red blood count, she said.

A similar approach was taken to identify other potential target antigens. Rezvani described developing CAR NK cells targeting CD70, which is expressed on a range of hematologic malignancies and solid tumors. After assessing 34 different CAR constructs, cells for infusion were prepared using the optimal construct and two optimal cord blood units. Rezvani said that 250 doses were manufactured at a calculated cost per infusion of $600, which is in stark contrast to the $500,000 per autologous CAR T cell therapy, and highlights the potential for these treatments to be more affordable and accessible (Jørgensen et al., 2025). Rezvani said that multiple clinical trials of CAR NK cells targeting different cancers are underway, and she is also studying a range of other applications for engineering NK cells.

___________________

⁴⁰ “A condition that occurs when donated stem cells or bone marrow (the graft) see the healthy tissues in the patient’s body (the host) as foreign and attack them.” See https://www.cancer.gov/publications/dictionaries/cancer-terms/def/graft-versus-host-disease (accessed August 22, 2025).

___________________

⁴¹ See https://integrotheranostics.com/science#page-section-6216b39e6f26322d74777fc3 (accessed October 6, 2025).

___________________

⁴² It is “usually found on the surface of normal prostate cells but is found in higher amounts on prostate cancer cells.” See https://www.cancer.gov/publications/dictionaries/cancer-terms/def/prostate-specific-membrane-antigen (accessed August 22, 2025).

artificial APCs were designed and administered subcutaneously to rescue a failing CAR T cell product (Zhang et al., 2025). Mooney said that biomaterial approaches are now being studied for potential applications across the T cell life cycle, such as enhancing thymic function, which could reduce a person’s susceptibility to cancer.

Hybrid Advanced Molecular Manufacturing Regulator for Cancer Immunotherapy

Omid Veiseh from Rice University said immunotherapy works extremely well for some patients, but only about 15 percent of patients with solid tumors respond effectively (Haslam and Prasad, 2019). Furthermore, patients can experience toxic effects before a therapeutic effect is achieved, particularly patients with peritoneal cancers. Studies of the immune environment of peritoneal tumors in patients treated with chemotherapy (e.g., carboplatin) have revealed reduced effector cell cytokine signaling, such as IL-12, IL-21, and IL-22, and higher levels of immune-suppressive cytokines, including macrophage colony-stimulating factor and transforming growth factor beta. This, Veiseh explained, results in an immune-suppressed tumor environment, which is no longer conducive for effector immunotherapy.

Veiseh and colleagues set out to develop a technology that could boost the solid tumor response rate, with the goal of reducing cancer-related deaths by at least 50 percent. He explained that with a grant from the Advanced Research Projects Agency for Health, a team of 19 investigators, including engineers, scientists, clinicians, and industry partners, is developing an implantable sense-and-respond device that monitors the tumor environment and produces immunomodulatory molecules as needed. This Hybrid Advanced Molecular Manufacturing Regulator for Cancer (HAMMR)⁴³ can adjust dosing in real time to improve therapeutic response and reduce toxicity.

Biologic cancer treatments undergo an extensive and expensive manufacturing process to produce and prepare them from engineered cells. In contrast, HAMMR is a biohybrid pharmacy that contains the engineered cells, biomaterials, and bioelectronics needed for personalized production and dosing of biologic therapies to the tumor environment. It leverages new biomaterial technologies that can encapsulate and protect allogeneic cells, allowing them to persist for years in multiple animal models, he said. Its sensors can measure the levels of up to six different cytokines every 5 minutes, he said. Controlled production of needed cytokines is elicited by electrical pulses, with real-time

___________________

⁴³ See https://news.rice.edu/news/2023/feds-fund-45m-rice-led-research-could-slash-us-cancer-deaths-50 (accessed August 22, 2025).

dose adjustment controlled by built-in AI. HAMMR can also monitor molecules associated with immune activation, such as interferon gamma.

In an ongoing Phase 1 dose escalation and safety clinical trial of cells engineered to produce a set level of IL-2, Veiseh said some participants with chemotherapy-resistant peritoneal ovarian cancers are experiencing improvement in progression-free survival, and no dose-limiting toxicities have been observed. Furthermore, analysis of T cells from the tumors of some participants indicated a dose-dependent increase in cytotoxic T lymphocyte (CTL)associated protein 4 expression, which Veiseh noted is a target for ipilimumab, a monoclonal antibody immunotherapy.

HAMMR is in preclinical testing in large animal models, and a first-in-human clinical trial is slated to launch in 2026. The goal, Veiseh said, is an internal, user-controlled bioelectronic device that enables long-term, controlled production and delivery of biologic medicines. He added that this type of system, where the clinician can monitor changes through the device and make adjustments remotely, provides opportunities to expand access to treatment.

Translational Opportunities in Cancer Mechanobiology

Cynthia Reinhart-King from Rice University discussed tumor angiogenesis as an example of using mechanobiology tools to understand cancer biology. Drawing on her work on tissue stiffening and vessel permeability in atherosclerosis, she had hypothesized that stiffening within tumors might also disrupt tumor blood vessel integrity. She described a study showing that the porosity of an endothelial cell monolayer increased with the stiffness of the underlaying gel support (Huynh et al., 2011). Similarly, endothelial spheroids demonstrated increased outgrowth in response to higher stiffness of the surrounding collagen matrix. A mouse mammary tumor model with chemical inhibition of matrix crosslinking showed that this was associated with reduced tumor stiffness, decreased vascularization, and lower permeability compared with stiffer tumors with normal crosslinking (Wang et al., 2019).

Reinhart-King explained that many investigational drugs that alter matrix stiffness have not been successful in clinical trials. In one study, she and colleagues found that inhibiting focal adhesion kinase could prevent the increased permeability associated with increasing matrix stiffness. She noted that a focal adhesion kinase-targeting drug is now approved to treat ovarian cancer. Studies also suggest a role for statins⁴⁴ in preventing cell response to matrix stiffness.

___________________

⁴⁴ “Statins inhibit a key enzyme that helps make cholesterol, [and] are being studied in the prevention and treatment of cancer.” See https://www.cancer.gov/publications/dictionaries/cancer-terms/def/statin (accessed August 22, 2025).

tory spaces but are expected to actively engage in community life. She said that this level of scientific integration positioned faculty, staff, fellows, and students to have conversations that would not happen otherwise.

Another important element of the institute model is its unique shared funding opportunities, said Hammond. She discussed the institute’s internal seed grants that enable principal investigators to rapidly initiate collaboration with other members; postdoctoral and graduate student fellowships; the Bridge Project,⁴⁵ which funds collaborations with local hospital partners on translating research to the clinic; and work at the Marble Center for Cancer Nanomedicine and the Center for Precision Medicine.

Hammond noted that social connections also help drive the model, and the institute is designed to foster both knowledge and community. “Innovations grow from these kinds of interactions both within the institute and with our neighbors,” she added. She explained that offsite scientific retreats, symposiums, student-run educational programs, outreach activities in the larger community, and numerous opportunities for conversations in common spaces advance social connections. Hammond said that the five keys to developing an interdisciplinary field of cancer engineering are learning to speak to and hear each other across fields; connecting researchers to clinicians and patients; providing resources geared toward accelerating cross-pollination; exchanging ideas together in an iterative fashion; and moving toward a shared goal.

MSK Cancer Center Engineering Program

Kayvan Keshari from the MSK Cancer Center described his early days at MSK as an engineer in a more cancer biology–driven organization. His focus was on developing new molecular imaging tools to describe cancer metabolism and inform engineering solutions for metabolic diagnostics and treatments. The result was developing hyperpolarized MRI and the necessary materials to visualize metabolic processes in vivo. Keshari said that creating these tools involved biological sciences, biochemical engineering, electrical engineering, and physics. A lesson from this experience, Kashari said, was that answering emerging questions in cancer biology requires more than just collaboration between biology and engineering. “It requires a new kind of engineer, one who speaks both languages,” he added.

Keshari noted that with philanthropic support and inspiration from the Koch Institute model discussed by Hammond, MSK established the Center for Molecular Imaging and Bioengineering. Keshari described building a community for research, including recruiting faculty, promoting collaboration with pilot grants, and bringing in international speakers for a cancer engineer-

___________________

⁴⁵ See https://www.dfhcc.harvard.edu/insider/for-researchers/funding/the-bridge-project/overview (accessed August 20, 2025).

ing seminar series. Another aspect of building the community is developing a pipeline of future cancer engineers, including establishing what Keshari said is the first cancer engineering Ph.D. program. He added that other pipeline elements include a seminar series for graduate students and postdoctoral fellows to present their work and a competitively selected 10-week summer engineering and imaging internship for undergraduate students.⁴⁶

Keshari said that targeted funding for cancer engineering education and training is needed, as these are not typically supported by traditional funding mechanisms. He suggested the need to establish cancer engineering academic departments and research institutes across the country to facilitate the convergence of cancer biology and engineering and develop multi-institutional partnerships to advance the field.

Translational Research Institute at Cedars-Sinai

Ze’ev Ronai from the Cedars-Sinai Medical Center Translational Research Institute first described working to establish the Technion Integrated Cancer Center in Israel, which brings together faculty in engineering, computer science, mathematics, biology, and oncology, and five affiliated hospitals, to develop novel technologies to benefit patients. He mentioned two examples of innovations that the center has developed: a novel MRI technology, which he said reduces scan time 10-fold, and a technology that captures single cells to study tumor heterogeneity.⁴⁷

Ronai said he is currently focused on using a computer-based approach to shorten the time from drug discovery to therapy. He said examples include in silico screening of small molecules to identify potential drug candidates and AI-based analyses enabling medicinal chemistry selection of analogs for further analysis. Another area of focus is computer-based precision oncology, Ronai added. He suggested that the future will involve more imaging for gene expression and less gene sequencing.

Ronai said that training is embedded across the Translational Research Institute, and graduate students and early-career trainees are integrated into all projects. In addition, seminars and workshops for trainees and mentoring opportunities for early-career Ph.D. scientists accelerate the path to promotion. He also mentioned an innovative, hands-on, 12-month, paid training program for recent college graduates who are headed to graduate school. “The pace of change in technology is much faster than we can imagine,” Ronai said, and the institute is monitoring the horizon and integrating advances.

___________________

⁴⁶ See https://www.mskcc.org/education-training/summer-scientific-undergraduate-programs/engineering-imaging-summer-program (accessed August 24, 2025).

⁴⁷ Itai Yanai, Uri Sivan, Elad Brod, Tamar Hashimshony, and Anatoly Senderovich. 2019. System and method for single cell genetic analysis. 10400273, filed February 4. 2016, and issued September 3, 2019.

cancer therapies are developed and delivered, including the convergence of RNA vaccines and technologies from the emerging field of mechanobiology. Chapman said several participants noted that novel approaches to drug development and distribution could increase innovation, accessibility, and affordability.

Regarding approaches to develop and expand the cancer engineering workforce, Rohan Fernandes from The George Washington University summarized some program elements presented by participants: shared building spaces that facilitate social and scientific interactions among researchers and students; shared funding opportunities to stimulate internal and external collaboration; and postdoctoral and graduate student fellowships. He reported that multiple panelists emphasized the importance of establishing collaborations among scientists, engineers, and clinicians from different disciplines and institutions to help foster innovation. Pettigrew said suggestions from the presentations included training researchers to communicate across fields and to clinicians and patients; creating opportunities for structured and unstructured interactions for ongoing exchange of ideas; developing the educational pipeline; investing in mentorship programs; and providing consistent funding to support and sustain collaborations and convergence.

Bhargava reported that multiple participants stressed the importance of science communication and effectively understanding and addressing the needs of the community to maximize the impact of science. Pettigrew closed by saying that including students in the workshop highlights their important role in taking cancer engineering into the future and realizing the vision of convergence.

This page intentionally left blank.