- Can you share a bit about your background and what motivated you to apply for and accept this Post-Doc fellowship with Fight CRC and Tempus?
I earned my PhD in Biologi
cal 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 FightCRC with expertise in computational cancer biology, machine learning, and CRC clinical care.
2. What is the primary focus of your research project during this fellowship? How has working with Tempus’ data and resources helped advance your work?
My primary focus is investigating therapeutic resistance mechanisms in metastatic CRCs. For example, we are studying how metastatic microsatellite stable (MSS) CRCs develop resistance to chemotherapy plus anti-VEGF or 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 for my work 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.
Progress and Findings
3. What are some of the early findings or insights from your research so far? Any surprising discoveries or challenges you’ve encountered?
For our project investigating how metastatic MSS CRC patients develop resistance to chemotherapy plus anti-EGFR therapy, we have observed that CRCs acquire both well studied and lesser known acquired resistance mutations after anti-EGFR therapy. The observation of lesser known acquired resistance mutations are interesting preliminary findings that we are continuing to investigate to understand if they may have utility in guiding clinical care.
4. How do you envision your research contributing to the broader field of colorectal cancer science?
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.
Data Impact
5. You mentioned that Tempus has built one of, if not, the largest CRC database in the world. What types of biomarkers and patient information can you analyze in this dataset?
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.
6. Looking at a large dataset like Tempus’, what kinds of patterns or insights are emerging that might not be visible in smaller datasets?
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.
Connection to Patients & Community
7. How does your research translate into potential impact for patients and caregivers?
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.
8. Have you had opportunities to engage with the Fight CRC patient community, and if so, how has that shaped your perspective?
Yes, I had the opportunity to meet with the FightCRC 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.
Partnership and Support
9. How has the partnership between Fight CRC and Tempus helped make your research possible?
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 FightCRC. This partnership also brings together leading scientists who help advise my research with expertise in computational cancer biology and machine learning at Tempus and FightCRC investigators with expertise in CRC clinical care. Of course, I’m biased but I think it’s a brilliant partnership to advance CRC research.
10. What does this kind of sustained grant support mean for an early-career researcher like yourself?
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.
Looking Forward
11. As this fellowship year wraps up, what are your hopes for the next stages of your research?
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.
12. What advice would you give other young scientists considering a career in cancer research?
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.