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Expert Opin Ther Targets. 2014 Dec;18(12):1407-20. doi: 10.1517/14728222.2014.955794. Epub 2014 Oct 21.

The PD-1 pathway as a therapeutic target to overcome immune escape mechanisms in cancer.

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Yale School of Medicine, Department of Internal Medicine, Resident in Internal Medicine , 333 Cedar Street, FMP 125, New Haven, CT 06520-8028 , USA.



Immunotherapy is emerging as a powerful approach in cancer treatment. Preclinical data predicted the antineoplastic effects seen in clinical trials of programmed death-1 (PD-1) pathway inhibitors, as well as their observed toxicities. The results of early clinical trials are extraordinarily promising in several cancer types and have shaped the direction of ongoing and future studies.


This review describes the biological rationale for targeting the PD-1 pathway with monoclonal antibodies for the treatment of cancer as a context for examining the results of early clinical trials. It also surveys the landscape of ongoing clinical trials and discusses their anticipated strengths and limitations.


PD-1 pathway inhibition represents a new frontier in cancer immunotherapy, which shows clear evidence of activity in various tumor types including NSCLC and melanoma. Ongoing and upcoming trials will examine optimal combinations of these agents, which should further define their role across tumor types. Current limitations include the absence of a reliable companion diagnostic to predict likely responders, as well as lack of data in early-stage cancer when treatment has the potential to increase cure rates.


cancer; immunotherapy; programmed death-1; programmed death-ligand 1

[Indexed for MEDLINE]

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