Determinants of resistance and response to melanoma therapy

Bailey M. Robertson; Mitchell E. Fane; Ashani T. Weeraratna; Vito W. Rebecca

doi:10.1038/s43018-024-00794-1

Determinants of resistance and response to melanoma therapy

Bailey M. Robertson
, Mitchell E. Fane
, Ashani T. Weeraratna
, Vito W. Rebecca

Bloomberg School of Public Health, Department of Oncology, Sidney Kimmel Cancer Center, School of Medicine, Johns Hopkins University

Research output: Contribution to journal › Review article › peer-review

49 Scopus citations

Abstract

Metastatic melanoma is among the most enigmatic advanced cancers to clinically manage despite immense progress in the way of available therapeutic options and historic decreases in the melanoma mortality rate. Most patients with metastatic melanoma treated with modern targeted therapies (for example, BRAFV600E/K inhibitors) and/or immune checkpoint blockade (for example, anti-programmed death 1 therapy) will progress, owing to profound tumor cell plasticity fueled by genetic and nongenetic mechanisms and dichotomous host microenvironmental influences. Here we discuss the determinants of tumor heterogeneity, mechanisms of therapy resistance and effective therapy regimens that hold curative promise.

Original language	English
Pages (from-to)	964-982
Number of pages	19
Journal	Nature Cancer
Volume	5
Issue number	7
DOIs	https://doi.org/10.1038/s43018-024-00794-1
State	Published - Jul 17 2024

Keywords

Drug Resistance, Neoplasm
Humans
Immune Checkpoint Inhibitors/therapeutic use
Melanoma/drug therapy
Molecular Targeted Therapy/methods
Proto-Oncogene Proteins B-raf/genetics
Skin Neoplasms/drug therapy
Tumor Microenvironment/drug effects

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10.1038/s43018-024-00794-1

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title = "Determinants of resistance and response to melanoma therapy",

abstract = "Metastatic melanoma is among the most enigmatic advanced cancers to clinically manage despite immense progress in the way of available therapeutic options and historic decreases in the melanoma mortality rate. Most patients with metastatic melanoma treated with modern targeted therapies (for example, BRAFV600E/K inhibitors) and/or immune checkpoint blockade (for example, anti-programmed death 1 therapy) will progress, owing to profound tumor cell plasticity fueled by genetic and nongenetic mechanisms and dichotomous host microenvironmental influences. Here we discuss the determinants of tumor heterogeneity, mechanisms of therapy resistance and effective therapy regimens that hold curative promise.",

keywords = "Drug Resistance, Neoplasm, Humans, Immune Checkpoint Inhibitors/therapeutic use, Melanoma/drug therapy, Molecular Targeted Therapy/methods, Proto-Oncogene Proteins B-raf/genetics, Skin Neoplasms/drug therapy, Tumor Microenvironment/drug effects",

author = "Robertson, \{Bailey M.\} and Fane, \{Mitchell E.\} and Weeraratna, \{Ashani T.\} and Rebecca, \{Vito W.\}",

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doi = "10.1038/s43018-024-00794-1",

language = "English",

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journal = "Nature Cancer",

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T1 - Determinants of resistance and response to melanoma therapy

AU - Robertson, Bailey M.

AU - Fane, Mitchell E.

AU - Weeraratna, Ashani T.

AU - Rebecca, Vito W.

PY - 2024/7/17

Y1 - 2024/7/17

N2 - Metastatic melanoma is among the most enigmatic advanced cancers to clinically manage despite immense progress in the way of available therapeutic options and historic decreases in the melanoma mortality rate. Most patients with metastatic melanoma treated with modern targeted therapies (for example, BRAFV600E/K inhibitors) and/or immune checkpoint blockade (for example, anti-programmed death 1 therapy) will progress, owing to profound tumor cell plasticity fueled by genetic and nongenetic mechanisms and dichotomous host microenvironmental influences. Here we discuss the determinants of tumor heterogeneity, mechanisms of therapy resistance and effective therapy regimens that hold curative promise.

AB - Metastatic melanoma is among the most enigmatic advanced cancers to clinically manage despite immense progress in the way of available therapeutic options and historic decreases in the melanoma mortality rate. Most patients with metastatic melanoma treated with modern targeted therapies (for example, BRAFV600E/K inhibitors) and/or immune checkpoint blockade (for example, anti-programmed death 1 therapy) will progress, owing to profound tumor cell plasticity fueled by genetic and nongenetic mechanisms and dichotomous host microenvironmental influences. Here we discuss the determinants of tumor heterogeneity, mechanisms of therapy resistance and effective therapy regimens that hold curative promise.

KW - Drug Resistance, Neoplasm

KW - Humans

KW - Immune Checkpoint Inhibitors/therapeutic use

KW - Melanoma/drug therapy

KW - Molecular Targeted Therapy/methods

KW - Proto-Oncogene Proteins B-raf/genetics

KW - Skin Neoplasms/drug therapy

KW - Tumor Microenvironment/drug effects

UR - https://doi.org/10.1038/s43018-024-00794-1

U2 - 10.1038/s43018-024-00794-1

DO - 10.1038/s43018-024-00794-1

M3 - Review article

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VL - 5

SP - 964

EP - 982

JO - Nature Cancer

JF - Nature Cancer

IS - 7

ER -

Determinants of resistance and response to melanoma therapy

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Reports Summarize Melanoma Findings from Johns Hopkins University (Determinants of Resistance and Response To Melanoma Therapy)

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Determinants of resistance and response to melanoma therapy

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Reports Summarize Melanoma Findings from Johns Hopkins University (Determinants of Resistance and Response To Melanoma Therapy)

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