Highlighted Scientific Opportunities in Cancer Research

The ability to quickly and affordably sequence the DNA of a patient’s tumor to understand what mutations are present has transformed precision medicine treatments in the last two decades. While this approach has been successful for many patients, most cancer patients do not currently have a genetic mutation that indicates a specific targeted treatment. That’s where functional precision medicine comes in. Samples of living patient-derived tissues and cells are exposed to different therapies to measure their effectiveness against that patient’s cancer. This allows scientists and clinicians to learn from a patient’s individual biology in real time and test multiple drugs simultaneously to make informed choices about what is most likely to work, increasing the chance that the right treatment can be provided to the right patient at the right time. 

A functional precision medicine approach can be particularly valuable when there isn’t a clear therapeutic option for a patient. This can be especially powerful when it is used in combination with patient tumor characteristics, such as its genetic profile, as well as other clinical data. Not only does this give insight into the patient’s individual treatment options, but it also has the potential to help researchers better understand biological vulnerabilities and tumor-drug interactions. Importantly, functional precision medicine has the potential to be used as a tool for personalized treatment decisions, especially for patients who have exhausted existing standards of care and who lack other good treatment options.

Decades of drug development and technological advances have set the stage for a new era of functional precision medicine providing expanded possibilities and tangible benefits for patients. Recent studies have shown success with functional precision medicine for some cancers, but we need to better understand which patients can benefit from this approach. For the field to progress, a strategic, coordinated, and focused national effort is necessary. 

To accelerate the development of functional precision medicine, further progress on patient-derived model development is needed.  Additionally, standards need to be established for deciding which assays to use for drug sensitivity testing and which biological markers are best to measure treatment effectiveness. More studies (both preclinical and clinical) and more data are needed to develop the functional precision medicine approach and build towards regulatory approvals.  

NCI has many opportunities to play a foundational role in functional precision medicine, and it can convene the cancer treatment community as this approach progresses. As the world’s largest funder of cancer research, NCI supports both intramural and extramural research and the associated infrastructure. This can spur needed basic research and clinical trials. NCI can also play a role in standardizing how patient tissues are handled and how results are reported. In this way, patient samples can be used most effectively and efficiently, allowing for the best treatment options. 

By investing in the technologies and standardization that drive the functional precision medicine approach, NCI can help catalyze a new era of improved treatment selection and better outcomes for cancer patients. 

One of the most exciting advances in the fight against cancer is the advent of adoptive cell-based immunotherapy, a personalized treatment that kills cancer by harnessing the ability of a patient’s own immune system to identify and eliminate abnormal cells. Cell-based immunotherapies have had remarkable success in the clinic, specifically in the treatment of blood cancers. Although early versions of these therapies showed limited efficacy in patients with other types of cancer, recent progress has led to the first approvals for solid tumors. With improvements enabling scalable and cost-effective production of cell-based immunotherapies, streamlined clinical trial pipelines, and continued research support, this treatment option will be available to more cancer patients.

Cell-based immunotherapies, also known as adoptive cell therapies, use living cells from patients to treat their disease. Traditionally, immune cells are collected from the patient’s blood or tumor tissue and then grown and modified in a lab to enable or enhance their cancer-fighting abilities before being reintroduced into the patient. As part of ongoing work to build upon this technology, researchers are currently testing in vivo cell-based immunotherapy techniques, which can modify immune cells directly inside the body.

The development of immunotherapy approaches has been a revolutionary innovation in cancer research. It has uncovered an entirely new and successful avenue for treating cancer. NCI-supported research led to the first cell-based immunotherapies, including chimeric antigen receptor T-cell (CAR T-cell) therapy, which were initially used to treat blood cancers. In 2024, an important milestone was achieved when the U.S. Food and Drug Administration (FDA) approved the first two cell-based immunotherapies for solid tumor cancers (tumor-infiltrating lymphocyte (TIL) therapy for melanoma and T-cell receptor (TCR) therapy for a type of soft tissue sarcoma), illustrating the growing potential of this kind of treatment for a wider range of cancer types.

Accelerating the development of new cell-based immunotherapies for more solid tumor cancers in adult and pediatric patients is a major focus of NCI. In part, this research has been done by its Center for Cancer Research and the Cancer Adoptive Cell Therapy (Can-ACT) Network, which uses cell manufacturing resources at NCI’s Frederick National Laboratory. This includes conducting and supporting small, early-phase clinical trials that evaluate the risks associated with experimental cell-based immunotherapies so they might be mitigated prior to testing in larger, later-phase trials. In addition, NCI’s efforts to coordinate, collect, and share results from NCI-supported cell-based immunotherapy trials are helping improve the clinical development of these therapies for use in patients.

NCI can further expand the reach of these treatments by addressing challenges related to treating solid tumors, reducing toxicity, and lowering manufacturing costs. With the help of technologies that measure biological activity at the single-cell level, researchers are gaining new insights into why some patients respond to these therapies while others do not. Advances in immunology are deepening our understanding of T-cells and other types of immune cells within the tumor microenvironment – the network of normal cells, molecules, and blood vessels that surround a tumor and affect how it grows and spreads. Researchers are also testing the effectiveness of combining cell-based immunotherapy with other treatment strategies, like cancer vaccines, while minimizing treatment-related toxicities and long-term side effects.

As new, cell-based immunotherapies are developed for a greater number of cancers, these treatments must be made more accessible. Currently, cell-based immunotherapies require specialized manufacturing processes to prepare patient cells. However, ongoing advances in cell modification techniques, such as those used for in vivo immunotherapy, can reduce the need for complex, lab-based cell manufacturing. Increased automation and infrastructure support also have the potential to lower costs and improve access for patients. Supporting a workforce trained in cell manufacturing and clinical delivery of cell-based immunotherapies will be necessary to improve manufacturing capacity, scalability, and availability, while assuring patient safety.

Continuing to develop therapies for solid tumors, lowering treatment costs, and simplifying clinical trial navigation can increase patient participation and ensure that all patients have access to innovative cell-based immunotherapies.

Childhood cancers are a leading cause of disease-related death in children. They also account for fewer than 1% of all cancer cases nationwide, making them more difficult to study. To address the limited availability of pediatric cancer data, NCI and the childhood cancer research community are working to improve the accessibility, integration, and reuse of these data. Researchers are leveraging comprehensive datasets in their studies to accelerate the discovery of better therapies, advance precision medicine approaches, and improve outcomes for children and adolescents and young adults (AYAs) experiencing cancer.

NCI’s Childhood Cancer Data Initiative (CCDI) partners with the patient, research, and clinical care communities to carry out nationwide collection and sharing of data on childhood cancers, regardless of where children receive their care. As part of CCDI, the Molecular Characterization Initiative (MCI), in collaboration with specimen collection efforts NCI supports through the Childhood Cancer STAR (Survivorship, Treatment, Access, Research) Act, facilitates rapid identification of key biological characteristics of patient tumors to inform treatment decisions in real time and make data available to both treating physicians and researchers. To date, more than 9,500 children and AYAs from all 50 states have participated. The STAR Act has also allowed NCI to support and expand the Childhood Cancer Survivor Study (CCSS), which has increased our understanding of survivorship outcomes and informed clinical guidelines to improve the long-term health of cancer survivors. CCDI incorporates data from CCSS, along with other NCI- and non-NCI-supported childhood and AYA cancer programs and networks and makes them available to researchers in the CCDI Data Hub.

Significant progress has been made in improving the collection and harmonization of pediatric cancer data available within CCDI. These data are especially important for studying childhood cancer types that still have no effective treatments, identifying therapies that cause unfavorable short- and long-term effects, and understanding why even the most successful treatments do not work for all patients. The application of artificial intelligence (AI) and advanced analytics to pediatric cancer data, which is prioritized in a 2025 Presidential Executive Order, has the potential to facilitate faster and more accurate diagnoses and improve understanding and prediction of treatment response and survivorship outcomes.

To make full use of these computational tools, high-quality data from multiple sources must be harmonized to ensure it is complete and standardized for interoperability. A childhood cancer research workforce well-trained in the analysis of large datasets and in the effective and responsible use of AI will benefit the evolving field of pediatric cancer research through the development of new insights and interventions. Improving data findability and accessibility, building specific pediatric cancer patient cohorts, and aggregating or linking datasets across multiple systems is essential for promoting collaboration and enabling more rapid research progress.

The collection, harmonization, and use of pediatric cancer data would not be possible without collaboration between NCI, the Centers for Disease Control and Prevention (CDC), the Office of the National Coordinator for Health Information Technology, and other government agencies, industry partners, researchers, clinicians, and most importantly, patients and their families. These partnerships enable the collection and use of pediatric cancer data, which is critical for advancing cancer research and improving outcomes for all patients.

Cancer is a dynamic disease that is unique to each patient. Tumor development and progression are complex, involving factors in the cancer cells themselves as well as multidimensional interactions between other cells and tissues in the body that are shaped by a person’s genetics and cumulative exposures. As cancer progresses, tumors typically become less uniform, composed of diverse combinations of cancer and noncancer cells with different molecular characteristics and behaviors. This staggering complexity makes it difficult to predict how a person’s cancer will progress and respond to treatment.

To address this complexity, NCI supports research to better understand how cancers develop from premalignant lesions to primary tumors to metastatic cancers. From this work, researchers hope to predict tumor progression and therapeutic responses to ultimately improve patient outcomes. Launched in 2018 by NCI, the Human Tumor Atlas Network (HTAN) is constructing 3-dimensional atlases of the cellular, structural, and molecular features of human cancers as they evolve from precancerous lesions to advanced disease. These dynamic maps provide biological and spatial information, allowing researchers to understand how different cells interact and change as tumors develop. As part of this Network, researchers are also developing tools to probe these features at single-cell resolution over time, as well as perfecting analytical methods for processing and interpreting spatial data. So far, 21 tissue sites from more than 2,000 patients have been used to create the 14 HTAN tumor atlases, including one pediatric atlas, that map the evolution of diverse cancer types.

HTAN has enabled exciting progress, including enhanced understanding of tumor-immune system interactions in solid tumors and identification of recurring spatial patterns that correlate with cancer progression over time. These results have spurred new insights into the underlying biology of tumor development and led more researchers to develop and adopt new tools and methodologies to more fully apply cancer atlas data.

While our understanding of tumor progression has advanced, thanks to the data and technology from tumor atlases, researchers are continuing to address challenges. For example, there is a need for additional studies to identify the underlying biological mechanisms leading to cancer progression, as well as the biomarkers that indicate response to therapy. There is great potential to leverage tools from other fields like engineering and advanced imaging, and advance technologies to integrate data across multiple comprehensive molecular profiles (“omics”) to better understand the dynamic nature of human systems.

Moving forward, it will be important to expand cancer atlas data usability and accessibility and foster a research community that can develop technologies along with advances in biology. We also need physicians to bring the insights gleaned from these atlases to the clinic for the benefit of their patients. These advances will be essential to fully leverage the rich datasets generated and ultimately predict a tumor’s trajectory and the best way to treat it. Additional research investments coupling tumor atlases with the underlying causes of disease, and advances in computer science and molecular techniques, will help enable precision prevention, treatment, and care strategies for patients.

Scientists have already amassed substantial knowledge from cancer atlas data; we can leverage these data for years to come, generating and validating exciting new scientific discoveries that provide a better understanding of the underlying biology of tumor development to predict tumor evolution and inform future therapeutic approaches.