Previously Funded Research

Chad Pecot, MD

University of North Carolina

Research Project:

Targeting the immune system to block the spread of lung squamous cancers

Summary:

While targeted therapies of lung adenocarcinoma have improved patient survival, similar advances in lung squamous carcinoma (LUSC) have been stagnant. Recent analyses of the genes that characterize LUSC have revealed they are highly idiosyncratic tumors with no clear “smoking gun” drug target. Recently, however, the use of new therapies that activate the immune system has demonstrated remarkable promise in LUSC.

We have uncovered a previously unrecognized group of LUSC patients whose tumors manipulate the immune system for its own advantage. Remarkably, this group accounts for nearly half of all LUSC patients. Through extensive analysis of the Cancer Genome Atlas (TCGA), as well as through novel cancer models we have developed, we found that LUSC metastasis are driven by immune cells called monocytes.

Here, we hypothesize that (i) blocking monocytes in LUSC will stop its spread and will be synergistic with already proven immune therapies, (ii) a gene signature we have developed will determine who will benefit from immune therapies, and (iii) that proteins in LUSC tumors will establish a biomarker of patients likely to respond to drugs blocking monocytes. The objectives of this proposal are 1) to determine the therapeutic role of targeting monocytes in LUSC, alone or in combination with a proven immune therapy, and 2) to develop predictive biomarkers of response to these novel immune therapies, which will be useful for design of an already planned Phase II clinical trial.