Keith T. Flaherty

Entering the Era of Combinatorial Therapy

Keith T. Flaherty, MD, holds the position of Associate Professor of Medicine at Harvard Medical School and Director of the Termeer Center for Targeted Therapy at the Massachusetts General Hospital Cancer Center, where he was recently named as the Richard Saltonstall Endowed Chair in Oncology. The goal of Dr. Flaherty's research is to understand the molecular and clinical consequences of inhibiting oncogenes and oncogenic pathways in melanoma, while establishing individual therapeutic approaches and constructing rational combinatorial therapies. A pioneer in developing targeted therapies matched to the genetic characteristics of a patient's tumor, Dr. Flaherty led early clinical trials on the development of vemurafenib and trametinib and the dabrafenib/trametinib combination.

Recent developments in targeted therapy and immunotherapy have revolutionized the treatment of melanoma; however, each of these approaches has limitations in overall response rates or duration of response. To improve the efficacy of both single-agent immune–targeted and signal-transduction–targeted therapy, Dr. Flaherty and other investigators have proposed combining these strategies, allowing for rational combinatorial regimens. Data from early efforts to build combinatorial regimens, as well as FDA drug approvals for melanoma, are discussed in the recently published CCR Drug Updates and CCR New Strategies articles written by Dr. Flaherty and his colleague Dr. Sullivan.

Dr. Flaherty is an active member of the American Association for Cancer Research (AACR), for which he serves as a Publications Committee member and a Clinical Cancer Research Senior Editor. He is also the Deputy Chair for Biomarker Sciences and the Chair of the Developmental Therapeutics Committee in the Eastern Cooperative Oncology Group, a Scientific Advisory Board member for the Melanoma International Foundation, and a Steering Committee member for the Society for Melanoma Research.

A selection of Dr. Flaherty's recent articles from the AACR family of journals is provided below:

• Pembrolizumab for treatment of patients with advanced or unresectable melanoma.
  Sullivan RJ, Flaherty KT. Clinical Cancer Research July 2015.
• New strategies in melanoma: entering the era of combinatorial therapy.
  Sullivan RJ, Flaherty KT. Clinical Cancer Research June 2015.
• EPHA2 is a mediator of vemurafenib resistance and a novel therapeutic target in melanoma.
  Miao B, Ji Z, Tan L, Taylor M, Zhang J, Choi HG, et al. Cancer Discovery March 2015.
• Universes collide: combining immunotherapy with targeted therapy for cancer.
  Wargo JA, Cooper ZA, Flaherty KT. Cancer Discovery December 2014.
• Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade.
  Cooper ZA, Juneja VR, Sage PT, Frederick DT, Piris A, Mitra D, et al. Cancer Immunology Research July 2014.