Melanoma: From Tumor-Specific Mutations to a New Molecular Taxonomy and Innovative Therapeutics

Tonnessen, Crystal A.; Haass, Nikolas K.

doi:10.1007/978-3-662-45840-2_2

Cited by 2 publications

(1 citation statement)

References 120 publications

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“…Targeted therapy of metastatic melanoma with MAPK pathway inhibitors holds great promise but suffers from rapid onset of resistance. The molecular mechanisms leading to drug resistance are discussed extensively in the literature [1]. Other possible contributing factors to drug sensitivity are tumor heterogeneity and differential biologic behavior, such as cell cycle progression, of melanoma cells in distinctive areas of the tumor [2].…”

Section: Editorialmentioning

confidence: 99%

Dynamic Tumor Heterogeneity in Melanoma Therapy: How do we Address this in a Novel Model System?

Haass

2015

Melanoma Manag.

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Section: Editorialmentioning

confidence: 99%

Dynamic Tumor Heterogeneity in Melanoma Therapy: How do we Address this in a Novel Model System?

Haass

2015

Melanoma Manag.

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Cell cycle‐tailored targeting of metastatic melanoma: Challenges and opportunities

Haass

Gabrielli

2017

Experimental Dermatology

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The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the "bad guy" to the "poster child" in oncology. Current targeted therapies are effective, although here is a clear need to develop combination therapies to delay the onset of resistance. Many antimelanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity.Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors. Secondly, if the combination is designed to target different tumor cell subpopulations of a heterogeneous tumor, one drug effective in a particular subpopulation should not negatively impact on the other drug targeting another subpopulation. In addition to the role of cell cycle stage and progression on standard chemotherapeutics and targeted drugs, we discuss the utilization of cell cycle checkpoint control defects to enhance chemotherapeutic responses or as targets themselves. We propose that cell cycle-tailored targeting of metastatic melanoma could further improve therapy outcomes and that our real-time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches. K E Y W O R D Scell cycle, drug resistance, drug sensitivity, fluorescent ubiquitination-based cell cycle indicator, melanoma therapy, real-time imaging

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Melanoma: From Tumor-Specific Mutations to a New Molecular Taxonomy and Innovative Therapeutics

Cited by 2 publications

References 120 publications

Dynamic Tumor Heterogeneity in Melanoma Therapy: How do we Address this in a Novel Model System?

Dynamic Tumor Heterogeneity in Melanoma Therapy: How do we Address this in a Novel Model System?

Cell cycle‐tailored targeting of metastatic melanoma: Challenges and opportunities

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