Previously Funded Research

Benjamin Drapkin, MD, PhD

Massachusetts General Hospital

Research Project:

Biomarker discovery for combination therapy with olaparib and temozolomide using patient-derived xenograft models of small cell lung cancer

Summary:

Small cell lung cancer (SCLC) afflicts more than 30,000 patients in the United States each year, and it is rapidly fatal in most cases. One of the challenges in developing new therapies is that even when outcomes are improved for a fraction of patients, there is no test to determine who will benefit. The goal of Dr. Drapkin’s project is to discover molecular features, or biomarkers, that can be used to predict benefit for experimental therapies. To discover these features, he has developed a platform to grow SCLC tumors from patients in mice using circulating tumor cells from blood. These models, called patient-derived xenografts (PDXs), are generated from patients entering clinical trials, both before treatment and after relapse. The PDX models can be studied to determine which features of the cancer predict response, and how the cancer becomes resistant.

At Massachusetts General Hospital, an early phase clinical trial was recently launched to test the combination of the PARP inhibitor olaparib and the DNA damaging agent temozolomide (O/T), for patients with relapsed SCLC. This trial has shown promising early results, with just under half of the patients experiencing significant tumor shrinkage. PDX models derived from trial have been treated with O/T, and their responses mirror the trial patient responses. These models will be used to identify biomarkers of O/T sensitivity and mechanisms of O/T resistance. The immediate impact will be to improve the design of further clinical trials of O/T in SCLC patients. In the longer term, this project may represent a new paradigm for the rapid refinement of promising therapies in SCLC, in which a clinical trial can be studied in the laboratory in real time through a concurrent co-clinical trial in PDX models.