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Novel Treatments in Development for Melanoma

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Melanoma

Part of the book series: Cancer Treatment and Research ((CTAR,volume 167))

Abstract

The past several years can be considered a renaissance era in the treatment of metastatic melanoma. Following a 30-year stretch in which oncologists barely put a dent in a very grim overall survival (OS) rate for these patients, things have rapidly changed course with the recent approval of three new melanoma drugs by the FDA. Both oncogene-targeted therapy and immune checkpoint blockade approaches have shown remarkable efficacy in a subset of melanoma patients and have clearly been game-changers in terms of clinical impact. However, most patients still succumb to their disease, and thus, there remains an urgent need to improve upon current therapies. Fortunately, innovations in molecular medicine have led to many silent gains that have greatly increased our understanding of the nature of cancer biology as well as the complex interactions between tumors and the immune system. They have also allowed for the first time a detailed understanding of an individual patient’s cancer at the genomic and proteomic level. This information is now starting to be employed at all stages of cancer treatment, including diagnosis, choice of drug therapy, treatment monitoring, and analysis of resistance mechanisms upon recurrence. This new era of personalized medicine will foreseeably lead to paradigm shifts in immunotherapeutic treatment approaches such as individualized cancer vaccines and adoptive transfer of genetically modified T cells. Advances in xenograft technology will also allow for the testing of drug combinations using in vivo models, a truly necessary development as the number of new drugs needing to be tested is predicted to skyrocket in the coming years. This chapter will provide an overview of recent technological developments in cancer research, and how they are expected to impact future diagnosis, monitoring, and development of novel treatments for metastatic melanoma.

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Abbreviations

TCGA:

The cancer genome atlas

PDX:

Patient-derived xenograft

BTLA:

B and T lymphocyte attenuator

CAR:

Chimeric antigen receptor

CTL:

Cytotoxic T lymphocyte

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

DC:

Dendritic cell

DLT:

Dose-limiting toxicity

IL-2:

Interleukin-2

IFA:

Incomplete Freund’s adjuvant

Mart-1:

Melanoma antigen recognized by T-cells 1

MAGE-A3:

Melanoma-associated antigen 3

NY-ESO1:

Cancer/testis antigen 1

TAA:

Tumor-associated antigen

TCR:

T-cell receptor

TGFbDNRII:

Transforming growth factor-beta dominant-negative receptor II

TIL:

Tumor-infiltrating lymphocyte

PD-1:

Programmed cell death protein 1

WES:

Whole exome sequencing

MHC:

Major histocompatibility complex

HLA:

Human leukocyte antigen

APC:

Antigen-presenting cell

TLR:

Toll-like receptor

REP:

Rapid expansion process

Tregs:

Regulatory T cells

Tscm:

Stem cell memory-like T cells

AICD:

Activation-induced cell death

CEA:

Carcinoembryonic

GD2:

Disialoganglioside

ERBB2:

Erb-b2 receptor tyrosine kinase 2

MAPK:

Mitogen-activated protein kinase

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Authors and Affiliations

  1. University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Chantale Bernatchez, Zachary A. Cooper, Jennifer A. Wargo, Patrick Hwu & Gregory Lizée

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  1. Chantale Bernatchez
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  2. Zachary A. Cooper
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  3. Jennifer A. Wargo
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  4. Patrick Hwu
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  5. Gregory Lizée
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Correspondence to Patrick Hwu .

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  1. Rutgers Cancer Institute of New Jersey, New Brunswick, New York, USA

    Howard L. Kaufman

  2. Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA

    Janice M. Mehnert

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Bernatchez, C., Cooper, Z.A., Wargo, J.A., Hwu, P., Lizée, G. (2016). Novel Treatments in Development for Melanoma. In: Kaufman, H., Mehnert, J. (eds) Melanoma. Cancer Treatment and Research, vol 167. Springer, Cham. https://doi.org/10.1007/978-3-319-22539-5_16

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