As Fight CRC’s three-year research fellowship with Tempus comes to a close, we’re proud to spotlight the incredible work of our current fellow, Matt Maxwell, whose efforts continue the legacy of innovation launched through this partnership. Building on the impactful research of inaugural fellow Dr. Ymke Van der Pol—whose projects advanced understanding of KRAS-mutated patient outcomes and optimal treatment strategies for BRAF V600E MSS colorectal cancer—Matt has carried this torch forward, helping identify critical gaps and opportunities in colorectal cancer research. As we wrap up this phase of our collaboration with Tempus, we celebrate Matt’s contributions and the future insights they’ll spark for the CRC community.

I earned my PhD in Biological Sciences at UC San Diego where my colleagues and I discovered a mechanism by which tumor cell ARID1A mutations can confer improved responsiveness to immunotherapy. This research provided a mechanistic explanation for prior reports that ARID1A mutations were enriched among patients who responded favorably to immunotherapy with certain types of cancer and provided a rationale for the development of novel combination therapies with the potential to increase immunotherapy efficacy.

For my postdoctoral fellowship, I decided to focus on precision oncology research with the goal of developing novel biomarkers that can better guide therapeutic selection for cancer patients. Tempus has built one of, if not the largest, colorectal cancer (CRC) databases in the world combining molecular profiling with patient treatment and outcomes data, making Tempus a perfect setting for precision oncology research in CRC. I accepted this fellowship both for the opportunity to work with Tempus’ expansive CRC database and to join a world-class team of scientists brought together by Tempus and Fight CRC with expertise in computational cancer biology, machine learning, and CRC clinical care.

My primary research focus is investigating therapeutic resistance mechanisms in metastatic CRC. For example, we are investigating why a subset of microsatellite instable (MSI) CRCs are resistant to immunotherapy and why a subset of microsatellite stable (MSS) CRCs without a RAS or RAF mutation (well-known resistance mechanisms) are resistant to chemotherapy plus anti-EGFR therapy. This research is important because it could enable us to develop biomarkers capable of predicting which patients are likely to develop resistance ahead of time and has the potential to inform the development of novel therapeutic approaches with increased efficacy.

The most important benefits of working with Tempus’ database are that it integrates multiple types of data such as molecular profiling and outcomes data, has a very large sample size of CRC patient samples, and is professionally maintained and well-organized.

In our research of MSI CRC immunotherapy resistance, we discovered novel molecular subtypes of MSI CRC that were associated with distinct tumor-immune profiles and patient outcomes following immunotherapy. In our project investigating MSS RAS/RAF non-mutant CRC resistance to anti-EGFR therapy, we were able to observe that certain rare mutations are associated with resistance to anti-EGFR therapy. Both projects have yielded exciting preliminary results that we are continuing to investigate to understand if our findings could translate into biomarkers with clinical utility and new targets for therapeutic development.

My hope is that our research will inspire new directions of research in the field on CRC therapy selection and therapeutic development. We are also starting to contribute to the CRC scientific community by establishing collaborations with other researchers in the field on topics such as molecular subtyping of CRC liver metastases and predicting sites of metastasis from early-stage CRCs.

Tempus’ data incorporates molecular profiling which allows us to include important CRC biomarkers in our analyses such as MSI/MSS status, KRAS mutations, BRAF mutations, and kinase gene fusions (e.g., NTRK/ALK/FGFR).

We can also classify CRC tumors based on their RNA expression profiles into consensus molecular subtypes (CMS) of CRC which have been associated with patient outcome. Tempus’ data also includes clinical characteristics such as tumor stage, tumor site, sidedness, age, sex, and ethnicity. Together, these data allow us to design highly detailed and clinically relevant research studies.

An advantage of working with large datasets such as Tempus’ is that you can discover rare patterns in the data and be confident that the patterns are real. In contrast, the same rare patterns in smaller datasets may be overlooked or treated as statistical noise during analysis due to limited sample size. For some of our future work on acquired resistance to specific chemotherapy regimens in metastatic MSS CRC, I hypothesize we may find rare patterns that are real and meaningful for patient care but would not be visible in smaller datasets.

There are two main areas of potential impact for patients and their families. The first is better guidance at critical decision points in patient treatment. For example, if we can develop a machine learning model that predicts a low chance of benefit from a standard treatment, clinicians can adjust their treatment strategy to avenues that may hold more promise. The second is in the development of more effective treatment regimens. If our research can uncover why some CRCs are resistant to therapy this could lay the groundwork for developing more effective treatment regimens aimed at targeting the mechanisms CRCs use to become resistant to therapy.

Yes, I had the opportunity to meet with the Fight CRC research advocates to share some of my research and hear their perspectives as survivors and caregivers. Learning more about the CRC patient community’s perspective has provided a deeper understanding of what clinical care looks and feels like from the patient point of view and serves as a source of motivation to continue making progress in the face of setbacks which are inevitable in scientific research.

The opportunity to study Tempus’ database of CRC patient samples has uniquely enabled me to pursue several high impact research questions and is only made possible by funding from Fight CRC. This partnership also brings together leading scientists who help advise my research with expertise in computational cancer biology and machine learning at Tempus and Fight CRC investigators with expertise in CRC clinical care. Of course, I’m biased but I think it’s a brilliant partnership to advance CRC research.

Sustained grant support means that we can tackle big questions that take time to adequately address. It also means that I can spend more time focused on research rather than continuously applying for funding which is very time consuming.

My hopes are that we can continue making progress on metastatic CRC precision oncology research, present at conferences, and publish work that we believe is robust and impactful so that it can be read by the wider scientific community. I’m also excited about investigating some new ideas involving target discovery to inform the development of novel therapeutics for MSS CRCs and predicting sites of metastasis from early-stage primary CRC tumors, which could have important clinical utility.

My advice would be to try research out for yourself either by joining a research laboratory during college if this is available to you or by applying to summer research internships (e.g., SURFs funded by NIH or REUs funded by NSF). It’s important to determine whether you are passionate about research via first-hand experience because research is filled with failures and setbacks so the passion for what you are doing is important to overcome these setbacks and make progress. If you find that you enjoy research, continue acquiring more research experience because the expertise you gain is cumulative and there’s a lot to learn. Cancer research is not an easy line of work, but it is one of the most intellectually stimulating fields that anyone could pursue and is very fulfilling because you are working towards making a positive impact for patients.