Our Research

 

Genomic characterization of squamous cell carcinomas

Our laboratory has played a major role in large scale genomic characterization studies of lung and head and neck cancers. This has included participation in The Cancer Genome Atlas as well as leading independent genomics projects at Dana-Farber and the Broad Institute.

Our goal moving forward is to use genomic techniques to study critical clinical and therapeutic questions in Oncology. The questions include the most basic understanding of genomic alterations in rare and understudied diseases, studies of tumor heterogeneity and evolution with therapy and understanding the molecular and genomic features which predict the natural history of the tumor and its response to therapy. We are fortunate at the Dana-Farber to have access to a rich repository of patient material and are studying these questions using a variety of genomic profiling methods principally in tumors from patients with squamous cell carcinomas of the lung, head and neck or skin.

 

Receptor tyrosine kinase alterations in squamous cell carcinomas of the lung and head and neck

We have identified the Fibroblast Growth Factor Receptor (FGFR) kinases as the most commonly altered tyrosine kinase family in lung and head and neck squamous cell carcinomas. FGFR kinase amplifications, mutations and fusions are found in these diseases and appear to be very promising therapeutic targets. We have built several cellular and animal models for the study of FGFR alterations in the laboratory and are exploring multiple areas of FGFR biology including the mechanisms of transformation of activating FGFR alterations, the efficacy of available and novel FGFR kinase targeted small molecule inhibitors, acquired resistance to anti-FGFR therapy and genomic characterization of novel FGFR variants. We are performing correlative studies in the context of ongoing clinical trials of FGFR inhibitors at the Dana-Farber so we can better understand which alterations are predictive of response to anti-FGFR therapy and which mechanisms of acquired resistance are clinically relevant. We are also exploring mechanisms by which lung and head and neck cancers may be rendered more sensitive to targeted therapies by understanding mechanisms which allow these cancers to survive therapy both acutely and in the long-term.

 

Immune system and cancer

One of the most promising novel therapeutic strategies in the therapy of patients with lung and other cancers is the use of new immunotherapeutic agents, principally those which target immune checkpoints. Our laboratory is using a variety of genomic assays to better understand how tumors remodel the immune microenvironment with the goal of using this information to develop rational and personalized immunotherapeutic strategies. We have shown that somatic and germline alterations in tumors can directly impact the composition of the immune microenvironment and are studying patient specimens to define mechanisms of response and resistance to immunotherapies. We are co-leading the TCGA PanCancer Immune Response group.

 

Cancer radiogenomics

Radiation therapy is broadly applied in the treatment of patients with cancer though it is not clear what governs the response of a given tumor to radiation. We have, through collaborations with colleagues in Radiation Oncology, developed methods to enable large scale profiling of tumors for radiation response to enumerate the genomic alterations which are predictive of response to radiation. This has also enabled high-throughput screening of cell lines for genomic correlates of radiation response and the development of novel radiosensitizers.

Address: 450 Brookline Avenue, Dana 810A, Boston, MA 02215
Telephone: 617-632-6335
FAX: 617-582-9830
E-mail: peter_hammerman@dfci.harvard.edu