Project title: Characterizing drug-tolerant persister cells in relapsed high grade neuroendocrine carcinomas

Carl M. Gay, MD, PhD The University of Texas MD Anderson Cancer Center

Carl M. Gay, MD, PhD
  • Status: Active
  • Year(s): 2022
  • Grant Type: Pilot
  • Research Type: Translational
  • Primary Tumor Site: Multiple
  • Area of Inquiry: Treatment resistance in high-grade NECs
  • Article/Video: Click Here


In his previous NETRF-supported research, Dr. Gay and his colleagues generated novel resources, including mouse and cell line models, derived from patients who have rare neuroendocrine carcinomas. In the newly funded work, the investigators plan to use these models to address a major unmet need in neuroendocrine carcinomas – namely how these tumors manage to persist and become treatment-resistant.

What critical NET problem/question will researchers try to answer?

Nearly all patients who have neuroendocrine carcinomas, regardless of the magnitude of their initial responses to therapy, will eventually relapse. This occurs even in cases where imaging tests suggest that the patients’ disease appears to have responded completely. Dr. Gay and his colleagues hypothesize that persister cells – cells that can survive and eventually proliferate despite effective chemotherapies – underlie this phenomenon and that they can identify and target these persister cells using the new models they developed. 

Why is this important?

Patients who experience terrific initial responses but inevitably relapse experience only modest improvements in their quality or quantity of life. Dr. Gay and his colleagues believe that if persister cells can be identified then they can be killed, and if they can be killed these terrific but transient treatment responses may lead to more durable remissions. 

What will the researchers do?

Using models of neuroendocrine carcinomas, Dr. Gay and his colleagues will trace the origin of and characterize the features of persister cells when these cancers are exposed to standard therapies for neuroendocrine carcinomas.

How might this improve treatment of NETs?

Dr. Gay and his team hope that their approach will lead to the identification of features of persister cells such that they can be prevented or reversed. 

What is the next step?

The next step is testing whether these persister cells can be prevented or killed with available drugs or developing new drugs to target them. 


Click below to watch an update from Dr. Gay.

Additional Details

  • City: Houston
  • State: TX
  • Country: United States
  • Grant Duration: 1 year
  • Sponsor: Martha O’Donnell Pagel Research Award


NETRF funds laboratory research to understand the development of neuroendocrine tumors and translational research to explore new concepts in treatment. Research grant descriptions and research updates from NETRF are not intended to serve as medical advice. It can take years for research discoveries to be fully validated and approved for patient care. Always consult your health care providers about your treatment options.

« Back to all funded research projects