Fifty percent of patients with lung adenocarcinoma will develop brain metastases. Patients frequently develop brain metastasis even while their extracranial disease remains under control. Unfortunately, treatment options are limited, and most current clinical trials in the US exclude patients with brain metastases. Our limited understanding of the molecular drivers of brain metastases has hampered the development of novel therapeutics for this common complication of cancer. Our group recently completed whole-exome sequencing of 104 brain metastases, primary tumors and normal tissue across many histologies. In this initial dataset, which included only 29 brain metastases from lung adenocarcinoma, we detected clinically actionable alterations that were unique to the brain metastases. We have now assembled a large cohort of lung adenocarcinoma brain metastases. Our proposed genomic analysis will focus on identifying and characterizing the molecular alterations in brain metastases from lung adenocarcinoma. We will analyze brain metastases and primary lung tumors and compare to lung cancers that do not metastasize. We will characterize these alterations using in vitro and in vivo assays of metastasis, including patient derived xenograft models. Identification of these mutations will aid in the design of more effective treatments for brain metastases.

Public Health Relevance

In this study, we propose to identify potential drivers and therapeutic targets of newly diagnosed and recurrent brain metastases from lung adenocarcinoma. Our application is relevant to the public health because there are no effective systemic therapies for patients with brain metastases from lung adenocarcinoma. Relevant to the NIH mission, the overarching objective of this study is to identify genetic changes that are associated with brain metastases, with the goal to identify optimal therapeutic approaches for this common neoplasm.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA227156-03
Application #
9924261
Study Section
Cancer Genetics Study Section (CG)
Program Officer
Dey, Sumana Mukherjee
Project Start
2018-05-01
Project End
2023-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114