Heterogeneity in Melanoma

Ng, Mei Fong; Simmons, Jacinta L.; Boyle, Glen M.

doi:10.3390/cancers14123030

Cited by 18 publications

(19 citation statements)

References 132 publications

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“…Targeting EMT, either through pathways enabling the EMT process, or characteristics of dedifferentiated post-EMT phenotypes, is an alluring approach to manage melanoma progression. However, tumor heterogeneity is a well-known contributor of therapy resistance as reviewed in ( 213 ), making the EMT process or products difficult targets. Applying tumor evolution algorithms and looking for shared markers across sub-clonal tumor populations may be able to overcome this problem in a search for shared vulnerabilities.…”

Section: Therapeutic Opportunities Against Immune Escape Emt and Earl...mentioning

confidence: 99%

Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy

Shirley,

Chhabra,

Amiri

et al. 2024

Front. Immunol.

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Melanoma is one of the most lethal neoplasms of the skin. Despite the revolutionary introduction of immune checkpoint inhibitors, metastatic spread, and recurrence remain critical problems in resistant cases. Melanoma employs a multitude of mechanisms to subvert the immune system and successfully metastasize to distant organs. Concerningly, recent research also shows that tumor cells can disseminate early during melanoma progression and enter dormant states, eventually leading to metastases at a future time. Immune escape and metastasis have previously been viewed as separate phenomena; however, accumulating evidence is breaking down this dichotomy. Recent research into the progressive mechanisms of melanoma provides evidence that dedifferentiation similar to classical epithelial to mesenchymal transition (EMT), genes involved in neural crest stem cell maintenance, and hypoxia/acidosis, are important factors simultaneously involved in immune escape and metastasis. The likeness between EMT and early dissemination, and differences, also become apparent in these contexts. Detailed knowledge of the mechanisms behind “dual drivers” simultaneously promoting metastatically inclined and immunosuppressive environments can yield novel strategies effective in disabling multiple facets of melanoma progression. Furthermore, understanding progression through these drivers may provide insight towards novel treatments capable of preventing recurrence arising from dormant dissemination or improving immunotherapy outcomes.

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Section: Therapeutic Opportunities Against Immune Escape Emt and Earl...mentioning

confidence: 99%

Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy

Shirley,

Chhabra,

Amiri

et al. 2024

Front. Immunol.

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“…Discordant BRAF mutation status has been observed in multiple investigations, which poses a significant problem for treatment selection and response. Metastases are genetically diverse in comparison to the primary tumor or other metastases from the same patient, as demonstrated by whole-genome sequencing analysis [ 60 , 61 ].…”

Section: Innovative Models For Future Rare Melanoma Researchmentioning

confidence: 99%

“…Mutually exclusive mutations have been identified in different tumor cell populations within a single tumor, and some subpopulations have been found to possess survival advantages that may impact treatment outcomes. Overall, the existence of intratumoral heterogeneity highlights the importance of personalized treatment approaches that target the specific subpopulations present within a tumor [ 60 , 61 ].…”

Section: Innovative Models For Future Rare Melanoma Researchmentioning

confidence: 99%

Experimental Models for Rare Melanoma Research—The Niche That Needs to Be Addressed

Ionita,

Malita,

Dehelean

et al. 2023

Bioengineering

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Melanoma, the tumor arising from the malignant transformation of pigment-producing cells—the melanocytes—represents one of the most severe cancer types. Despite their rarity compared to cutaneous melanoma, the extracutaneous subtypes such as uveal melanoma (UM), acral lentiginous melanoma (ALM), and mucosal melanoma (MM) stand out due to their increased aggressiveness and mortality rate, demanding continuous research to elucidate their specific pathological features and develop efficient therapies. Driven by the emerging progresses made in the preclinical modeling of melanoma, the current paper covers the most relevant in vitro, in vivo, and in ovo systems, providing a deeper understanding of these rare melanoma subtypes. However, the preclinical models for UM, ALM, and MM that were developed so far remain scarce, and none of them is able to completely simulate the complexity that is characteristic to these melanomas; thus, a continuous expansion of the existing library of experimental models is pivotal for driving advancements in this research field. An overview of the applicability of precision medicine in the management of rare melanoma subtypes is also provided.

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“…Thus, marketing authorization of different drugs and/or combinations has taken place [107][108][109]. However, intra and intertumoral heterogeneity continues to overlap, limiting therapeutic success [107,110,111], but according to the ClinicalTrials.gov database, a large number of clinical trials have been carried out testing new therapeutic strategies, including those based on nanotechnology.…”

Section: Challenges and Opportunities For Cutaneous Melanoma Treatmentmentioning

confidence: 99%

Melanoma Management: From Epidemiology to Treatment and Latest Advances

Lopes

Rodrigues

Gaspar

et al. 2022

Cancers

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Melanoma is the deadliest skin cancer, whose morbidity and mortality indicators show an increasing trend worldwide. In addition to its great heterogeneity, melanoma has a high metastatic potential, resulting in very limited response to therapies currently available, which were restricted to surgery, radiotherapy and chemotherapy for many years. Advances in knowledge about the pathophysiological mechanisms of the disease have allowed the development of new therapeutic classes, such as immune checkpoint and small molecule kinase inhibitors. However, despite the incontestable progress in the quality of life and survival rates of the patients, effectiveness is still far from desired. Some adverse side effects and resistance mechanisms are the main barriers. Thus, the search for better options has resulted in many clinical trials that are now investigating new drugs and/or combinations. The low water solubility of drugs, low stability and rapid metabolism limit the clinical potential and therapeutic use of some compounds. Thus, the research of nanotechnology-based strategies is being explored as the basis for the broad application of different types of nanosystems in the treatment of melanoma. Future development focus on challenges understanding the mechanisms that make these nanosystems more effective.

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Heterogeneity in Melanoma

Cited by 18 publications

References 132 publications

Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy

Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy

Experimental Models for Rare Melanoma Research—The Niche That Needs to Be Addressed

Melanoma Management: From Epidemiology to Treatment and Latest Advances

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