Melanoma: A Therapeutic Revolution Happening Before Our Eyes

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Roberto Anaya-Prado Heli Hernández-González Andres Insunza-Martin del Campo Michelle M. Anaya-Fernández Consuelo C. Azcona-Ramírez Roberto Anaya-Fernández Bryan Urueta-Chávez Liam N Méndez-Bisgaard Juan A. Delgado-Vázquez Adriana D. García-Romero

Abstract

Malignant melanoma (MM) is among the most common cancers in the world. Although incidence has been increasing worldwide, most of the cases have been reported to occur in the European continent. Risk factors for the development of MM have been clearly recognized; yet, the accepted theory is that the risk of melanoma is highly determined by the interplay between genetic factors and exposure to sunlight. Morphological characteristics classify melanoma into four subtypes: Superficial spreading melanoma (SSM); nodular melanoma (NM), Lentigo maligna (LM) and Acral lentiginous melanoma (ALM). SSM represents approximately 70% of the cases. Mitogen-activated protein kinase (MAPK) has been identified as a key regulatory element in most melanomas. MAPK is the most relevant signal pathway in the development of melanoma; while the microphthalmia-associated transcription factor (MITF) is a target of extracellular signal-related kinase (ERK) and controls the production of the pigment melanin, cell cycling and survival. Surgical resection is still considered the cornerstone of the treatment in the vast majority of patients with early-stage melanoma. However, treatment of metastatic or recurrent melanoma has significantly been improved with the advent of targeted immunotherapies. The greatest advantage has been observed with the use of checkpoint-inhibitor immunotherapy. But, Adoptive cell therapy (ACT) for the treatment of metastatic melanoma, in patients who have progressed to immunotherapy and/or targeted therapies without success, is currently under investigation with promising results.

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How to Cite
ANAYA-PRADO, Roberto et al. Melanoma: A Therapeutic Revolution Happening Before Our Eyes. Medical Research Archives, [S.l.], v. 10, n. 7, july 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2848>. Date accessed: 14 aug. 2022. doi: https://doi.org/10.18103/mra.v10i7.2848.
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References

1. International Agency for Reserch on Cancer. Melanoma of skin ASR. Glob Cancer Obs [Internet]. 2020;1–2. Available at: http://globocan.iarc.fr/old/bar_sex_site.asp?selection=16120&title=Melanoma+of+skin&statistic=2&populations=6&window=1&grid=1&color1=5&color1e=&color2=4&color2e=&submit=Execute (Last visited Abril 30th, 2022)
2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2018;68(6):394–424
3. Karimkhani C, Green AC, Nijsten T, Weinstock MA, Dellavalle RP, Naghavi M, et al. The global burden of melanoma: results from the Global Burden of Disease Study 2015. Br J Dermatol 2017;177(1):134–40
4. Garbe C, Leiter U. Melanoma epidemiology and trends. Clin Dermatol 2009;27(1):3–9
5. Ostrowski SM, & Fisher D. Biology of Melanoma. Hematology/Oncology Clinics Of North America 2021;35(1):29-56
6. Zanetti R, Rosso S, Martinez C, Nieto A, Miranda A, Mercier M, et al. Comparison of risk patterns in carcinoma and melanoma of the skin in men: A multi-centre case-case-control study. Br J Cancer 2006;94(5):743–51
7. Lasithiotakis KG, Leiter U, Gorkievicz R, Eigentler T, Breuninger H, Metzler G, et al. The incidence and mortality of cutaneous melanoma in Southern Germany: Trends by anatomic site and pathologic characteristics, 1976 to 2003. Cancer 2006;107(6):1331–9
8. Demierre MF, Chung C, Miller DR, Geller AC. Early detection of thick melanomas in the United States: Beware of the nodular subtype. Arch Dermatol 2005;141(6):745–50
9. Swetter SM, Boldrick JC, Jung SY, Egbert BM, Harvell JD. Increasing incidence of lentigo maligna melanoma subtypes: Northern California and national trends 1990-2000. J Invest Dermatol 2005;125(4):685–91
10. Coleman WP 3rd, Loria PR, Reed RJ, Krementz ET. Acral lentiginous melanoma. Arch Dermatol 1980;116(7):773-6
11. Elder DE, Bastian BC, Cree IA, Massi D, Scolyer RA. The 2018 World Health Organization classification of cutaneous, mucosal, and uveal melanoma detailed analysis of 9 distinct subtypes defined by their evolutionary pathway. Arch Pathol Lab Med 2020;144(4):500–22
12. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009;27(36):6199–206
13. Teixido C, Castillo P, Martinez-Vila C, Arance A, Alos L. Molecular markers and targets in melanoma. Cells 2021;10(9):2320
14. Smalley KSM, Sondak VK. Melanoma — An Unlikely Poster Child for Personalized Cancer Therapy. N Engl J Med 2010;363(9):876–8
15. Noonan FP, Zaidi MR, Wolnicka-Glubisz A, Anver MR, Bahn J, Wielgus A, et al. Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment. Nat Commun 2012;3:884
16. Omholt K, Platz A, Kanter L, Ringborg U, Hansson J. NRAS and BRAF Mutations Arise Early during Melanoma Pathogenesis and Are Preserved throughout Tumor Progression. Clin Cancer Res 2003;9(17):6483–8
17. Akbani R, Akdemir KC, Aksoy BA, Albert M, Ally A, Amin SB, et al. Genomic Classification of Cutaneous Melanoma. Cell 2015;161(7):1681–96
18. Krauthammer M, Kong Y, Bacchiocchi A, Evans P, Pornputtapong N, Wu C, et al. Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas. Nat Genet 2015;47(9):996–1002
19. Beeram M, Patnaik A, Rowinsky EK. Raf: A strategic target for therapeutic development against cancer. J Clin Oncol 2005;23(27):6771–90
20. Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, et al. High frequency of BRAF mutations in nevi. Nat Genet 2003;33(1):19–20
21. Wellbrock C, Hurlstone A. BRAF as therapeutic target in melanoma. Biochem Pharmacol 2010;80(5):561–7
22. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation. N Engl J Med 2011;364(26):2507–16
23. Bollag G, Hirth P, Tsai J, Zhang J, Ibrahim PN, Cho H, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 2010;467(7315):596–9
24. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 2010;464(7287):427–30
25. Solit DB, Garraway LA, Pratilas CA, Sawai A, Getz G, Basso A, et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006;439(7074):358–62
26. Sarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, et al. Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. J Clin Oncol 2021;39(24):2656–66