Precision oncology is still in its infancy, and while groups envision personalizing care based on the responses of individual tumors there are a wide array of potential uses for the data generated by precision medicine pipelines. Examining data from iterative drug screening performed in collaboration with the Englander Institute of Precision Medicine this project seeks to examine the molecular mechanisms that underpin the efficacy of two PI3K inhibitor based combinations. Specifically aim one explore the impact of the PLK phosphorylation of both wildtype and mutant PI3K to understand the ramifications of this interaction and to identify patient populations who could benefit from combination treatment with PLK and PI3K inhibitors.
The second aim seeks to understand the impact of the insulin release that occurs with PI3K inhibitor treatments, and to ask if therapeutic responses can be improved by preventing this feedback. In this manner this project will seek to explain the molecular mechanisms that underlie observations from our precision medicine pipeline and seek to identify patient populations that would benefit from these therapeutic approaches.

Public Health Relevance

Cancer is a devastating set of diseases and while genomics can identify the genetic alterations that drive these diseases translating this data into effective clinical strategies is still not possible for many patients. The goal of this work is to understand the molecular mechanisms that drive tumor responses to two combinations identified through precision medicine drug screening so that these approaches, which focus on targeting the PI3K signaling pathway, can be effectively deployed in future clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Transition Award (R00)
Project #
5R00CA230384-03
Application #
9963156
Study Section
Special Emphasis Panel (NSS)
Program Officer
O'Hayre, Morgan
Project Start
2019-07-01
Project End
2022-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Genetics
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029