Outcome of combination therapy using BRAF and MEK inhibitors among Asian patients with advanced melanoma: An analysis of 112 cases

Fujisawa, Yasuhiro; Ito, Takamichi; Katô, Hiroshi; Irié, Hiroyuki; Kaji, Tatsuru; Maekawa, Takeo; Asai, Jun; Yamamoto, Yuki; Fujimura, Taku; Nakai, Yasuo; Yasuda, Masahito; Matsuyama, Katsuhiko; Muto, Ikko; Matsushita, Satoru; Uchi, Hiroshi; Nakamura, Yoshiyuki; Uehara, Jiro; Yoshino, Koji

doi:10.1016/j.ejca.2020.12.021

Cited by 34 publications

(35 citation statements)

References 24 publications

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“…For the minority of metastatic MM patients who harbour BRAF mutations, combined inhibition of BRAF and MEK may represent a valid therapeutic opportunity, as this combination therapy already showed an impressive response rate and survival benefit in BRAFV600E/K positive cutaneous melanoma (CM) patients [142]. Indeed, a Japanese retrospective study evaluating BRAF and MEK inhibition also in MM with BRAF mutations reported similar response rates of those achieved for CM (64.3% vs. 76.5%) patients [143]. Furthermore, for patients with NRAS, NF1 or SPRED1 alterations, a potential therapeutic strategy may be represented by targeting the downstream protein MEK.…”

Section: Targeted Therapymentioning

confidence: 99%

Anorectal and Genital Mucosal Melanoma: Diagnostic Challenges, Current Knowledge and Therapeutic Opportunities of Rare Melanomas

et al. 2022

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Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM. In this overview, focused on anorectal and genital MM as models of rare melanomas deserving of a multidisciplinary approach, we highlight the need of referring these patients to centers with experts in melanoma, anorectal and uro-genital cancers treatments. Taking into account the rarity, the poor outcomes and the lack of effective treatment options for MM, tailored research needs to be promptly promoted.

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Section: Targeted Therapymentioning

confidence: 99%

Anorectal and Genital Mucosal Melanoma: Diagnostic Challenges, Current Knowledge and Therapeutic Opportunities of Rare Melanomas

et al. 2022

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“…Furthermore, drug resistance is easily developed, especially in Asian population. 8,9 There is an unmet need for effective therapy in patients with progressive melanoma, especially those resistant to BRAF inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Curcumin suppresses cell proliferation and triggers apoptosis in vemurafenib‐resistant melanoma cells by downregulating the EGFR signaling pathway

Chiu

Yang

Tsai

et al. 2022

Environmental Toxicology

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Melanoma is a malignant tumor with aggressive behavior. Vemurafenib, a BRAF inhibitor, is clinically used in melanoma, but resistance to melanoma cytotoxic therapies is associated with BRAF mutations. Curcumin can effectively inhibit numerous types of cancers. However, there are no reports regarding the correlation between curcumin and vemurafenib-resistant melanoma cells. In this study, vemurafenibresistant A375.S2 (A375.S2/VR) cells were established, and the functional mechanism of the epidermal growth factor receptor (EGFR), serine-threonine kinase (AKT), and the extracellular signal-regulated kinase (ERK) signaling induced by curcumin was investigated in A375.S2/VR cells in vitro. Our results indicated that A375.S2/VR cells had a higher IC 50 concentration of vemurafenib than the parental A375.S2 cells. Moreover, curcumin reduced the viability and confluence of A375.S2/VR cells. Curcumin triggered apoptosis via reactive oxygen species (ROS) production, disruption of mitochondrial membrane potential (ΔΨ m), and intrinsic signaling (caspase-9/-3-dependent) pathways in A375.S2/VR cells. Curcumin-induced apoptosis was also mediated by the EGFR signaling pathway. Combination treatment with curcumin and gefitinib (an EGFR inhibitor) synergistically potentiated the inhibitory effect of cell viability in A375.S2/VR cells. The present study provides new insights into the Yu-Jen Chiu and Jai-Sing Yang contributed equally to this study.

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“…E + B combination therapy is one of the first-line therapies for advanced melanoma that is recommended by several guidelines for cutaneous melanoma [ 1 , 2 ], and it is known to develop a different profile of AEs compared with dabrafenib plus trametinib (D + T) combination therapy [ 3 , 6 ]. For example, one of the characteristic AEs of E + B combination therapy is serous retinal detachment [ 3 , 4 , 5 ], whereas a characteristic AE of D + T combination therapy is pyrexia [ 6 , 7 , 8 ]. However, a case of tubulointerstitial nephritis as an AE of E + B combination therapy was limited in all of these clinical studies [ 3 , 4 , 5 ].…”

Section: Discussionmentioning

confidence: 99%

Tubulointerstitial Nephritis in an Advanced Melanoma Patient Treated with Encorafenib plus Binimetinib Combination Therapy

et al. 2022

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Encorafenib plus binimetinib combination therapy is one of the first-line therapies for advanced melanoma, and it is known to cause a different profile of adverse events (AEs) than dabrafenib plus trametinib combination therapy. Of such AEs, tubulointerstitial nephritis caused by BRAF plus MEK inhibitors combination therapy is limited. In this report, a case of tubulointerstitial nephritis that developed in a rheumatoid arthritis patient with advanced melanoma treated with encorafenib plus dabrafenib combination therapy is presented.

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Outcome of combination therapy using BRAF and MEK inhibitors among Asian patients with advanced melanoma: An analysis of 112 cases

Cited by 34 publications

References 24 publications

Anorectal and Genital Mucosal Melanoma: Diagnostic Challenges, Current Knowledge and Therapeutic Opportunities of Rare Melanomas

Anorectal and Genital Mucosal Melanoma: Diagnostic Challenges, Current Knowledge and Therapeutic Opportunities of Rare Melanomas

Curcumin suppresses cell proliferation and triggers apoptosis in vemurafenib‐resistant melanoma cells by downregulating the EGFR signaling pathway

Tubulointerstitial Nephritis in an Advanced Melanoma Patient Treated with Encorafenib plus Binimetinib Combination Therapy

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