Associate Professor of Radiation Oncology Harvard Medical School

Associate Radiation Oncologist Radiation Oncology, Massachusetts General Hospital

Clinician-Scientist and Principal Investigator Radiation Oncology, Mass General Research Institute

Director, Radiation Biology and Research Program Radiation Oncology, Massachusetts General Hospital

Director, Thoracic Radiation Oncology Service Cancer Center, Massachusetts General Hospital

Clinicn Investigator, Assc Prf Radiology, Mass General Research Institute

MD Universitaet Hamburg Medical School 1994

biomarker discovery; cancer biology; drug screening assays antitumor; egfr; kras; lung cancer; precision medicine; radiation biology; radioresistance; radiosensitizers

The precision medicine revolution has provided radiation oncologists with tremendous opportunities to enhance the anti-tumor effects of radiation therapy, potentially with less normal tissue toxicity than traditional chemotherapeutics. As a result, my laboratory is committed to identifying molecular targeted drugs and predictive biomarkers that can be used to enhance and personalize radiation therapy. We are particularly interested in lung cancer, a disease that is often difficult to eradicate by radiation, owing to large size and aggressive biological behavior. Novel treatment approaches are urgently needed to overcome lung cancer radiation resistance. We are keen on applying knowledge gained from our lung cancer studies to the treatment of other cancer types, including head and neck, pancreatic, and liver cancers. The lab also has special expertise in targeting DNA repair in cancers, which can be used to enhance the effects of many anti-cancer therapies, including proton radiation or PARP inhibitors.

Focus Areas in the Willers Lab:

1. 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.

2. Identifying radiosensitizing 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. Part of the NCI U01 supported Preclinical Chemo-Radiotherapy Testing Consortium.

3. Exploiting altered DNA repair in 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.