We currently have three interrelated focus areas:
Understand and Target Radioresistance of Cancers:
Elucidate mechanisms of genotype-correlated radioresistance in lung cancer and identify biological targets to overcome that resistance.
We are particularly interested in a better understanding of radioresistance conferred by mutated KRAS. Recent findings have given given us new clues which hopefully will translate into novel treatments in the near future. We are also active in pursuing KRAS as a biomarker to guide the use of radiation therapy in clinical practice.
Identify Radiosensitizing Targeted Drugs:
Develop a precision radiation medicine screening platform for testing of novel radiosensitizing drugs in lung cancer cell lines and 3D cultures and identification of genomic biomarkers.
Here we address an urgent problem in radiation oncology, how to identify and proper validate radiosensitizing drugs before bringing them into clinical trials. Leveraging the unique resources of the MGH Cancer Center we have successfully implemented a screening platform with > 500 drug/cell line combinations tested to date, including several that target KRAS-mutated cancers.
Therapeutically Exploit Altered DNA Repair in Cancers:
Target DNA repair and response pathways in lung cancer, in order to personalize DNA damaging therapies.
We are particularly interested in targeting DNA repair pathways in tumors that are controlled by EGFR. We recently described how EGFR-mutated tumor cells are sensitive to PARP inhibitors which we seek to clinical translate. We also discovered that certain alterations in DNA repair in cancers renders the affected tumors sensitive to proton beam radiation. Developing DNA repair biomarkers to guide the use of proton beam therapy, particularly in patients with EGFR-mutated tumors, is a major current research focus.