Role of Anti-PD-1 Antibodies in Advanced Melanoma: The Era of Immunotherapy

Abstract

Advanced melanoma is an aggressive skin cancer characterized by poor survival rates and response to cytotoxic chemotherapy. Immune checkpoint inhibitors are novel agents capable of utilizing one’s own immune system to bring about the tumor destruction. Nivolumab and pembrolizumab are fully humanized anti-PD-1 monoclonal antibodies that have shown significant anti-tumor activity in a variety of cancers including melanoma and have significantly improved the survival outcomes in patients with advanced melanoma. In this updated review article, we will discuss the outcomes of various clinical trials evaluating the efficacy and safety of these agents. We will also briefly discuss their mechanism of action and adverse effects.

Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

“…Thus PD-1 and other receptors like it act as an immune checkpoint to prevents an autoimmune response [458,459]. Binding of pembrolizumab to PD-1 blocks the receptor-ligand interaction and allows the immune system to attack cancer cells [460]. Although we do not discuss them here, nivolumab is another anti PD-1 antibody, while atezolizumab, avelumab, and durvalumab are anti PD-L1 antibodies that have been FDA approved [461,462].…”

Malignant melanoma types and treatment

“…The purpose of immunotherapy is to fundamentally target these checkpoints, inhibit tumor tolerance, and as a result, eliminate tumor cells. [28] In recent years, our understanding of the role of the immune system in the control of tumor proliferation has led to the success of therapies targeted to act upon immune pathways, especially in melanoma. Cancer cells nullify immune mechanisms with escape mechanisms.…”

“…The most well-known inhibitor receptors are cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death receptor 1 (PD-1). [28,29]…”

Primary and acquired resistance mechanisms to immune checkpoint inhibition in Hodgkin lymphoma

“…At the forefront of immune checkpoint therapy are antibodies targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and the programmed cell death-1 (PD-1). However, clinical success of immune checkpoint inhibitors greatly varies between different cancer types, ranging from objective responses in 65-87% of Hodgkin lymphoma (HL) patients to around 30% in other malignancies [reviewed by [1][2][3]].…”