title: Combining targeted therapy and immune checkpoint inhibitors in the treatment of metastatic melanoma.
abstract: Melanoma is the deadliest form of skin cancer and has an incidence that is rising faster than any other solid tumor. Metastatic melanoma treatment has considerably progressed in the past five years with the introduction of targeted therapy (BRAF and MEK inhibitors) and immune checkpoint blockade (anti-CTLA4, anti-PD-1, and anti-PD-L1). However, each treatment modality has limitations. Treatment with targeted therapy has been associated with a high response rate, but with short-term responses. Conversely, treatment with immune checkpoint blockade has a lower response rate, but with long-term responses. Targeted therapy affects antitumor immunity, and synergy may exist when targeted therapy is combined with immunotherapy. This article presents a brief review of the rationale and evidence for the potential synergy between targeted therapy and immune checkpoint blockade. Challenges and directions for future studies are also proposed.
authors.affiliation: 1 Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Harvard Medical School, Boston, MA 02115, USA ; 3 Department of Melanoma Medical Oncology, 4 Department of Genomic Medicine, 5 Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Kim
authors.affiliation: 1 Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Harvard Medical School, Boston, MA 02115, USA ; 3 Department of Melanoma Medical Oncology, 4 Department of Genomic Medicine, 5 Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Rodabe N
authors.initials: RN
authors.lastname: Amaria
authors.affiliation: 1 Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Harvard Medical School, Boston, MA 02115, USA ; 3 Department of Melanoma Medical Oncology, 4 Department of Genomic Medicine, 5 Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Spencer
authors.affiliation: 1 Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Harvard Medical School, Boston, MA 02115, USA ; 3 Department of Melanoma Medical Oncology, 4 Department of Genomic Medicine, 5 Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reuben
authors.affiliation: 1 Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Harvard Medical School, Boston, MA 02115, USA ; 3 Department of Melanoma Medical Oncology, 4 Department of Genomic Medicine, 5 Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Cooper
authors.affiliation: 1 Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Harvard Medical School, Boston, MA 02115, USA ; 3 Department of Melanoma Medical Oncology, 4 Department of Genomic Medicine, 5 Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wargo
keywords: BRAF inhibition; Melanoma; checkpoint blockade; immunotherapy