The American Association for Cancer Research Annual Meeting 2024 will mark the 10th anniversary of the AACR’s NextGen Stars Program by welcoming in a class of 10 outstanding early-career scientists. Since 2014, the program has supported the professional advancement of graduate students, postdocs, and assistant professors by providing highly visible opportunities to present scientific findings at the Annual Meeting.

Hear from one of the newest NextGen Stars in their own words, below, and click here to read Q&As with other members of the NextGen Stars Class of 2024.

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Arnav Mehta, MD, PhD

AACR NextGen Stars Class of 2024
Assistant in Medicine
Massachusetts General Hospital, Boston, Massachusetts

Abstract Presentation:
NG08 – Dissecting and quantifying pancreatic cancer plasticity using single-cell multiomics, lineage tracing, and functional genomics reveals novel mediators of therapy resistance

Session Details:
AOS06 – Unwrapping Heterogeneity in Pancreatic Cancer
Tuesday, April 9, 10:15 – 11:45 a.m. PT
Ballroom 6 CF, Upper Level, Convention Center

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What is the subject of your research?
Pancreatic cancer is a lethal disease with 5-year survival rates right around 10%. Over the past two decades, genetic and transcriptomic studies have begun to characterize subtypes of tumor cells that may have prognostic implications. The subtypes are actively being defined, but the two major ones are described basal and classical tumors. Basal tumors have been purported to be more chemotherapy resistant, and as such, portend worse overall prognosis. More recently, several lines of evidence suggest that classical cells can adopt basal features to evade therapy – thus exhibiting plasticity, which was recently noted to be an emerging hallmark of cancer. Our work focuses on: 1) using lineage tracing to definitively prove plasticity exists in patient-derived pancreatic cancer models, 2) using state-of-the art single-cell genomics to study the behavior of plastic cells and identify what genes might be influencing this behavior, and 3) using CRISPR editing to perturb genes that influence plasticity to better understand the therapeutic implications of this. Using these methods we have uncovered several novel regulators of plasticity that may be altered in combination with current therapies to improve patient outcomes.

What sparked your interest in this area of research, and why is it important?
During my oncology fellowship years, I spent the majority of my time caring for gastrointestinal cancer patients. It became apparent to me early on that despite having one of the most lethal cancers, patients with pancreatic cancer have limited treatment options beyond first and second line chemotherapy. Despite innovation in combination chemotherapy, we as a field have only been able to move the needle marginally when it comes to patient outcomes. This drove me to spend time on the underlying tumor biology and immunology of gastrointestinal cancers, particularly pancreatic cancer. The core goals of our research are to identify mechanisms that underlie treatment resistance, both in the context of current chemotherapy treatment paradigms and emerging targeted therapy such as KRAS inhibitors. Importantly, as both a computationalist and experimentalist, I felt we were uniquely positioned to build the experimental tools and then to answer key questions around plasticity quantitatively that would enable the discovery of novel targets.

What (or who) inspired you to apply for the NextGen Stars program?
Several of my current and past mentors, including Dr. Andy Aguirre and Dr. Will Hwang, have been fortunate to present at AACR as NextGen Stars. I have been inspired by the presentations of the past and by the science that is being done in the labs of several of the scientists who have recently presented.

What are you looking forward to as a member of the NextGen Stars?
I am looking forward to being part of a community of forward-thinking scientists taking disparate approaches towards important questions in oncology. I hope to use the opportunity to share our framework for understanding pancreatic cancer therapy resistance more broadly and forge new collaborations towards the questions we are interested in studying towards patient benefit.