Determine Radioresistance of Cancers We seek to elucidate mechanisms of radioresistance in lung and other cancers and identify biological targets to overcome that resistance.
We are particularly interested in a better understanding of radioresistance conferred by co-mutated KRAS and TP53. 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
We have established a precision radiation medicine screening platform for testing of novel radiosensitizing drugs in cancer cell lines and 3D cell cultures and for identifying 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 aim to screening > 8,000 drug/cell line combinations, with a particular focus on targeting KRAS-mutated cancers.
We aim to 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 the EGFR. We recently described how EGFR-mutated tumor cells are sensitive to PARP inhibitors which is currently being tested in a clinical trial based on this work.
We also discovered that certain alterations in DNA repair in cancers render the affected tumors sensitive to proton beam radiation. Developing DNA repair biomarkers to guide the use of proton beam therapy is a major current research focus.