Melanoma: oncogenic drivers and the immune system

Abstract

Advances and in-depth understanding of the biology of melanoma over the past 30 years have contributed to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. The finding that oncogenic BRAF mutations drive tumor growth in up to 50% of melanomas led to a molecular therapy revolution for unresectable and metastatic disease. Moving beyond BRAF, inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided targets for cancer immunotherapy. In this review, we discuss the molecular biology of melanoma and we focus on the recent advances of molecularly targeted and immunotherapeutic approaches.

Keywords: BRAF; Melanoma; biology; immune system; resistance; targeted therapies.

Figure 1

Key pathways and therapeutic targets in melanoma. Designed using the ingenuity pathway analysis (IPA) software (Available online: https://www.ingenuity.com/). PKC, protein kinase C; ERAS, ES cell-expressed Ras; NRG-1, neuregulin; MITF, microphthalmia-associated transcription factor.

Figure 2

Signaling pathways of main checkpoints molecules. Designed using the ingenuity pathway analysis (IPA) software (Available online: https://www.ingenuity.com/). APC, antigen-presenting cells; TCR, T cell receptor; TIM3, T cell immunoglobulin and mucin domain-containing 3; LAG3, lymphocyte activation gene 3 protein; mTOR, major histocompatibility complex mammalian target of rapamycin.