Skip to main content Skip to main navigation menu Skip to site footer
  • Register
  • Login
  • Menu
  • Home
  • Current
  • Archives
  • Announcements
  • About
    • About the Journal
    • Submissions
    • Editorial Team
    • Privacy Statement
    • Contact
  • Register
  • Login

Quality in Sport

Advances in Targeted Therapies and Combination Approaches for Melanoma: A Comprehensive Review
  • Home
  • /
  • Advances in Targeted Therapies and Combination Approaches for Melanoma: A Comprehensive Review
  1. Home /
  2. Archives /
  3. Vol. 23 (2024) /
  4. Medical Sciences

Advances in Targeted Therapies and Combination Approaches for Melanoma: A Comprehensive Review

Authors

  • Magda Przestrzelska Wydział Medyczny. Collegium Medicum. Uniwersytet Kardynała Stefana Wyszyńskiego w Warszawie https://orcid.org/0009-0009-8688-7047
  • Iga Ślesicka Mazovian Specialized Hospital in Ostrołęka of Józef Psarski, Jana Pawła II 120A, 07-410 Ostrołęka https://orcid.org/0000-0001-7282-4875
  • Natalia Zozula District Medical Center in Grójec Piotra Skargi 10 street, 05-600 Grójec https://orcid.org/0009-0009-9741-5061
  • Zuzanna Tomczewska Provincial Specialist Hospital named after Blessed Father Jerzy Popiełuszko in Włocławek, Wieniecka 49, 87-800 Włocławek https://orcid.org/0000-0002-4327-3311
  • Aleksandra Rykucka Rear Admiral Professor Wiesław Łasiński 7th Military Navy Hospital with Outpatient Clinic named after in Gdańsk Polanki 117 street, 80-305 Gdańsk https://orcid.org/0009-0003-0171-8647
  • Marcin Wąs District Medical Center in Grójec Piotra Skargi 10 street, 05-600 Grójec https://orcid.org/0009-0004-8645-0121
  • Aleksandra Latała District Medical Center in Grójec Piotra Skargi 10 street, 05-600 Grójec https://orcid.org/0009-0007-1701-2728
  • Justyna Kiełbasa Independent Public Healthcare Complex in Pruszków 2/4 Armii Krajowej Avenue, 05-800 Pruszków https://orcid.org/0009-0002-0616-7402
  • Agata Kowalczyk Mazovian Specialized Hospital in Ostrołęka of Józef Psarski, Jana Pawła II 120A, 07-410 Ostrołęka https://orcid.org/0009-0007-9497-0970
  • Katarzyna Bil Independent Public Specialist Western Hospital named after St John Paul II, Daleka 11, 05-825 Grodzisk Mazowiecki https://orcid.org/0009-0003-6518-1711

DOI:

https://doi.org/10.12775/QS.2024.23.54869

Keywords

melanoma, targeted therapy, immunotherapy

Abstract

Introduction and Purpose: Melanoma, an aggressive malignancy from melanocytes, has a poor prognosis. Despite advances in targeted therapies and immunotherapies, drug resistance remains a challenge. This review examines the molecular pathways involved in melanoma and therapeutic strategies targeting them, aiming to improve patient outcomes and overcome treatment resistance by understanding genetic alterations and signaling cascades driving melanoma progression.

State of Knowledge: Melanoma arises from genetic predisposition and UV radiation exposure, involving mutations in pathways like RAS/RAF/MAPK and PI3K/AKT. Targeted therapies, such as BRAF and MEK inhibitors, are effective, especially in BRAF-mutant patients. However, resistance mechanisms, including alternative pathway activation and immune evasion, limit their long-term success. Combination therapies with immunotherapies show promise in overcoming resistance. Emerging targets like NRAS, c-KIT, and c-MET offer new treatment possibilities. Ongoing challenges include identifying biomarkers for patient stratification and managing treatment-related toxicity.

Conclusions: Understanding the molecular mechanisms of melanoma is crucial for advancing therapies. Targeted therapies and combination approaches have improved outcomes, especially in advanced cases. However, challenges like treatment resistance and toxicity require ongoing research. By exploring signaling pathways and new targets, treatment efficacy and durability can be enhanced. Continued research and clinical trials are essential to translate these advancements into practice, improving survival rates and quality of life for melanoma patients.

References

Böni R, Schuster C, Nehrhoff B, Burg G. Epidemiology of skin cancer. Neuro Endocrinol Lett. 2002;23 Suppl 2:48-51.

Khan AQ, Travers JB, Kemp MG. Roles of UVA radiation and DNA damage responses in melanoma pathogenesis. Environ Mol Mutagen. 2018;59(5):438-460. doi:10.1002/em.22176

Montor, W.R.; Salas, A.; Melo, F.H.M. Receptor tyrosine kinases and downstream pathways as druggable targets for cancer treatment: The current arsenal of inhibitors. Mol. Cancer 2018, 17, 55.

Schrank Z, Chhabra G, Lin L, et al. Current Molecular-Targeted Therapies in NSCLC and Their Mechanism of Resistance. Cancers (Basel). 2018;10(7):224. Published 2018 Jul 4. doi:10.3390/cancers10070224

Carr S, Smith C, Wernberg J. Epidemiology and Risk Factors of Melanoma. Surg Clin North Am. 2020;100(1):1-12. doi:10.1016/j.suc.2019.09.005

O'Neill CH, Scoggins CR. Melanoma. J Surg Oncol. 2019;120(5):873-881. doi:10.1002/jso.25604

Iglesias-Pena N, Paradela S, Tejera-Vaquerizo A, Boada A, Fonseca E. Cutaneous Melanoma in the Elderly: Review of a Growing Problem. Actas Dermo-Sifiliográficas. 2019;110(6):434-447. doi:10.1016/j.adengl.2019.05.012

Bevona C, Goggins W, Quinn T, Fullerton J, Tsao H. Cutaneous Melanomas Associated With Nevi. Archives of Dermatology. 2003;139(12):1620-1624. doi:10.1001/archderm.139.12.1620

Davis LE, Shalin SC, Tackett AJ. Current state of melanoma diagnosis and treatment. Cancer Biology & Therapy. 2019;20(11):1366-1379. doi:10.1080/15384047.2019.1640032

Michielin O, van Akkooi ACJ, Ascierto PA, Dummer R, Keilholz U; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019;30(12):1884-1901. doi:10.1093/annonc/mdz411

Czarnecka AM, Bartnik E, Fiedorowicz M, Rutkowski P. Targeted Therapy in Melanoma and Mechanisms of Resistance. Int J Mol Sci. 2020;21(13):4576. Published 2020 Jun 27. doi:10.3390/ijms21134576

Luke JJ, Flaherty KT, Ribas A, Long GV. Targeted agents and immunotherapies: optimizing outcomes in melanoma. Nat Rev Clin Oncol. 2017;14(8):463-482. doi:10.1038/nrclinonc.2017.43

Namikawa K, Yamazaki N. Targeted Therapy and Immunotherapy for Melanoma in Japan. Curr Treat Options Oncol. 2019;20(1):7. Published 2019 Jan 24. doi:10.1007/s11864-019-0607-8

Smalley KSM. Understanding Melanoma Signaling Networks as the Basis for Molecular Targeted Therapy. Journal of Investigative Dermatology. 2010;130(1):28-37. doi:10.1038/jid.2009.177

Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. The Lancet. 2012;380(9839):358-365. doi:10.1016/S0140-6736(12)60868-X

Robert Caroline, Karaszewska Boguslawa, Schachter Jacob, et al. Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib. New England Journal of Medicine. 2015;372(1):30-39. doi:10.1056/NEJMoa1412690

Subbiah V, Baik C, Kirkwood JM. Clinical Development of BRAF plus MEK Inhibitor Combinations. Trends in Cancer. 2020;6(9):797-810. doi:10.1016/j.trecan.2020.05.009

Yu C, Liu X, Yang J, et al. Combination of Immunotherapy With Targeted Therapy: Theory and Practice in Metastatic Melanoma. Front Immunol. 2019;10:990. Published 2019 May 7. doi:10.3389/fimmu.2019.00990

Sun J, Zager JS, Eroglu Z. Encorafenib/binimetinib for the treatment of BRAF-mutant advanced, unresectable, or metastatic melanoma: design, development, and potential place in therapy. Onco Targets Ther. 2018;11:9081-9089. Published 2018 Dec 14. doi:10.2147/OTT.S171693

Koelblinger P, Thuerigen O, Dummer R. Development of encorafenib for BRAF-mutated advanced melanoma. Curr Opin Oncol. 2018;30(2):125-133. doi:10.1097/CCO.0000000000000426

Sullivan R, LoRusso P, Boerner S, Dummer R. Achievements and Challenges of Molecular Targeted Therapy in Melanoma. Am Soc Clin Oncol Educ Book. 2015;(35):177-186. doi:10.14694/EdBook_AM.2015.35.177

Dummer R, Long GV, Robert C, et al. Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma. J Clin Oncol. 2022;40(13):1428-1438. doi:10.1200/JCO.21.01601

Hodis E, Watson IR, Kryukov GV, et al. A landscape of driver mutations in melanoma. Cell. 2012;150(2):251-263. doi:10.1016/j.cell.2012.06.024

Devitt B, Liu W, Salemi R, et al. Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma. Pigment Cell Melanoma Res. 2011;24(4):666-672. doi:10.1111/j.1755-148X.2011.00873.x

Thomas NE, Edmiston SN, Alexander A, et al. Association Between NRAS and BRAF Mutational Status and Melanoma-Specific Survival Among Patients With Higher-Risk Primary Melanoma [published correction appears in JAMA Oncol. 2015 Jun;1(3):285]. JAMA Oncol. 2015;1(3):359-368. doi:10.1001/jamaoncol.2015.0493

Kelleher FC, McArthur GA. Targeting NRAS in melanoma. Cancer J. 2012;18(2):132-136. doi:10.1097/PPO.0b013e31824ba4df

Sosman JA, Kittaneh M, Lolkema MPJK, et al. A phase 1b/2 study of LEE011 in combination with binimetinib (MEK162) in patients with NRAS-mutant melanoma: Early encouraging clinical activity. JCO. 2014;32(15_suppl):9009-9009. doi:10.1200/jco.2014.32.15_suppl.9009

Atefi M, Titz B, Avramis E, et al. Combination of pan-RAF and MEK inhibitors in NRAS mutant melanoma. Mol Cancer. 2015;14(1):27. Published 2015 Feb 3. doi:10.1186/s12943-015-0293-5

Adam C, Fusi L, Weiss N, et al. Efficient Suppression of NRAS-Driven Melanoma by Co-Inhibition of ERK1/2 and ERK5 MAPK Pathways. J Invest Dermatol. 2020;140(12):2455-2465.e10. doi:10.1016/j.jid.2020.03.972

Hong David S., Fakih Marwan G., Strickler John H., et al. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. New England Journal of Medicine. 2020;383(13):1207-1217. doi:10.1056/NEJMoa1917239

Vanni I, Tanda ET, Dalmasso B, et al. Non-BRAF Mutant Melanoma: Molecular Features and Therapeutical Implications. Front Mol Biosci. 2020;7:172. Published 2020 Jul 24. doi:10.3389/fmolb.2020.00172

Wan X, Liu R, Li Z. The Prognostic Value of HRAS mRNA Expression in Cutaneous Melanoma. Biomed Res Int. 2017;2017:5356737. doi:10.1155/2017/5356737

Portelinha A, Thompson S, Smith RA, et al. ASN007 is a selective ERK1/2 inhibitor with preferential activity against RAS-and RAF-mutant tumors. Cell Rep Med. 2021;2(7):100350. Published 2021 Jul 21. doi:10.1016/j.xcrm.2021.100350

Crosier PS, Ricciardi ST, Hall LR, Vitas MR, Clark SC, Crosier KE. Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia. Blood. 1993;82(4):1151-1158.

Maulik G, Bharti A, Khan E, Broderick RJ, Kijima T, Salgia R. Modulation of c-Kit/SCF pathway leads to alterations in topoisomerase-I activity in small cell lung cancer. J Environ Pathol Toxicol Oncol. 2004;23(4):237-251. doi:10.1615/jenvpathtoxoncol.v23.i4.10

Crosier PS, Ricciardi ST, Hall LR, Vitas MR, Clark SC, Crosier KE. Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia. Blood. 1993;82(4):1151-1158.

Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24(26):4340-4346. doi:10.1200/JCO.2006.06.2984

Tuveson DA, Willis NA, Jacks T, et al. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene. 2001;20(36):5054-5058. doi:10.1038/sj.onc.1204704

Wei X, Mao L, Chi Z, et al. Efficacy Evaluation of Imatinib for the Treatment of Melanoma: Evidence From a Retrospective Study. Oncol Res. 2019;27(4):495-501. doi:10.3727/096504018X15331163433914

Meng D, Carvajal RD. KIT as an Oncogenic Driver in Melanoma: An Update on Clinical Development. Am J Clin Dermatol. 2019;20(3):315-323. doi:10.1007/s40257-018-0414-1

Sierra JR, Tsao MS. c-MET as a potential therapeutic target and biomarker in cancer. Ther Adv Med Oncol. 2011;3(1 Suppl):S21-S35. doi:10.1177/1758834011422557

Peschard P, Park M. From Tpr-Met to Met, tumorigenesis and tubes. Oncogene. 2007;26(9):1276-1285. doi:10.1038/sj.onc.1210201

Knudsen BS, Vande Woude G. Showering c-MET-dependent cancers with drugs. Current Opinion in Genetics & Development. 2008;18(1):87-96. doi:10.1016/j.gde.2008.02.001

Puri N, Ahmed S, Janamanchi V, et al. c-Met Is a Potentially New Therapeutic Target for Treatment of Human Melanoma. Clinical Cancer Research. 2007;13(7):2246-2253. doi:10.1158/1078-0432.CCR-06-0776

Patel M, Eckburg A, Gantiwala S, Hart Z, Dein J, Lam K, Puri N. Resistance to Molecularly Targeted Therapies in Melanoma. Cancers. 2021; 13(5):1115. https://doi.org/10.3390/cancers13051115

Etnyre D, Stone AL, Fong JT, et al. Targeting c-Met in melanoma: mechanism of resistance and efficacy of novel combinatorial inhibitor therapy. Cancer Biol Ther. 2014;15(9):1129-1141. doi:10.4161/cbt.29451

Cheng H, Terai M, Kageyama K, et al. Paracrine Effect of NRG1 and HGF Drives Resistance to MEK Inhibitors in Metastatic Uveal Melanoma. Cancer Res. 2015;75(13):2737-2748. doi:10.1158/0008-5472.CAN-15-0370

Puri N, Ahmed S, Janamanchi V, et al. c-Met Is a Potentially New Therapeutic Target for Treatment of Human Melanoma. Clinical Cancer Research. 2007;13(7):2246-2253. doi:10.1158/1078-0432.CCR-06-0776

Ohara M, Saito K, Kageyama K, et al. Dual Targeting of CDK4/6 and cMET in Metastatic Uveal Melanoma. Cancers (Basel). 2021;13(5):1104. Published 2021 Mar 4. doi:10.3390/cancers13051104

Leonardi GC, Falzone L, Salemi R, et al. Cutaneous melanoma: From pathogenesis to therapy (Review). Int J Oncol. 2018;52(4):1071-1080. doi:10.3892/ijo.2018.4287

Schram AM, Gandhi L, Mita MM, et al. A phase Ib dose-escalation and expansion study of the oral MEK inhibitor pimasertib and PI3K/MTOR inhibitor voxtalisib in patients with advanced solid tumours. Br J Cancer. 2018;119(12):1471-1476. doi:10.1038/s41416-018-0322-4

Downloads

  • PDF

Published

2024-10-04

How to Cite

1.
PRZESTRZELSKA, Magda, ŚLESICKA, Iga, ZOZULA, Natalia, TOMCZEWSKA, Zuzanna, RYKUCKA, Aleksandra, WĄS, Marcin, LATAŁA, Aleksandra, KIEŁBASA, Justyna, KOWALCZYK, Agata and BIL, Katarzyna. Advances in Targeted Therapies and Combination Approaches for Melanoma: A Comprehensive Review. Quality in Sport. Online. 4 October 2024. Vol. 23, p. 54869. [Accessed 25 December 2025]. DOI 10.12775/QS.2024.23.54869.
  • ISO 690
  • ACM
  • ACS
  • APA
  • ABNT
  • Chicago
  • Harvard
  • IEEE
  • MLA
  • Turabian
  • Vancouver
Download Citation
  • Endnote/Zotero/Mendeley (RIS)
  • BibTeX

Issue

Vol. 23 (2024)

Section

Medical Sciences

License

Copyright (c) 2024 Magda Przestrzelska, Iga Ślesicka, Natalia Zozula, Zuzanna Tomczewska, Aleksandra Rykucka, Marcin Wąs, Aleksandra Latała, Justyna Kiełbasa, Agata Kowalczyk, Katarzyna Bil

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Stats

Number of views and downloads: 279
Number of citations: 0

Search

Search

Browse

  • Browse Author Index
  • Issue archive

User

User

Current Issue

  • Atom logo
  • RSS2 logo
  • RSS1 logo

Information

  • For Readers
  • For Authors
  • For Librarians

Newsletter

Subscribe Unsubscribe

Tags

Search using one of provided tags:

melanoma, targeted therapy, immunotherapy
Up

Akademicka Platforma Czasopism

Najlepsze czasopisma naukowe i akademickie w jednym miejscu

apcz.umk.pl

Partners

  • Akademia Ignatianum w Krakowie
  • Akademickie Towarzystwo Andragogiczne
  • Fundacja Copernicus na rzecz Rozwoju Badań Naukowych
  • Instytut Historii im. Tadeusza Manteuffla Polskiej Akademii Nauk
  • Instytut Kultur Śródziemnomorskich i Orientalnych PAN
  • Instytut Tomistyczny
  • Karmelitański Instytut Duchowości w Krakowie
  • Ministerstwo Kultury i Dziedzictwa Narodowego
  • Państwowa Akademia Nauk Stosowanych w Krośnie
  • Państwowa Akademia Nauk Stosowanych we Włocławku
  • Państwowa Wyższa Szkoła Zawodowa im. Stanisława Pigonia w Krośnie
  • Polska Fundacja Przemysłu Kosmicznego
  • Polskie Towarzystwo Ekonomiczne
  • Polskie Towarzystwo Ludoznawcze
  • Towarzystwo Miłośników Torunia
  • Towarzystwo Naukowe w Toruniu
  • Uniwersytet im. Adama Mickiewicza w Poznaniu
  • Uniwersytet Komisji Edukacji Narodowej w Krakowie
  • Uniwersytet Mikołaja Kopernika
  • Uniwersytet w Białymstoku
  • Uniwersytet Warszawski
  • Wojewódzka Biblioteka Publiczna - Książnica Kopernikańska
  • Wyższe Seminarium Duchowne w Pelplinie / Wydawnictwo Diecezjalne „Bernardinum" w Pelplinie

© 2021- Nicolaus Copernicus University Accessibility statement Shop