Cutaneous Melanoma

When combined with anti-PD-L1 monoclonal antibodies, the treatment achieved synergistic tumor regression, improved effector T cell function, and induced durable immunological memory, demonstrating significant inhibition of both primary and distant tumors in murine models. Collectively, this work presents a transdermal brachytherapeutic-immunomodulatory strategy for melanoma treatment, offering promising potential for enhanced antitumor immunotherapy.

P1, N=41, Terminated, Seagen, a wholly owned subsidiary of Pfizer | Active, not recruiting --> Terminated; The trial was terminated for strategic reasons. The decision was not based on any safety concerns.

P1, N=65, Active, not recruiting, Genentech, Inc. | Trial completion date: Jun 2027 --> Dec 2026 | Trial primary completion date: Jun 2027 --> Dec 2026

P1, N=75, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

This profile mirrors patterns reported in neighbouring Arab and Eastern Mediterranean populations and contrasts with more lightly pigmented (Fitzpatrick I-II) Western populations. The findings underline the need for improved melanoma awareness, routine examination of acral and mucosal sites, and strengthened cancer registration in Palestine.

P2, N=35, Completed, Melanoma Institute Australia | Active, not recruiting --> Completed

This study elucidates the potential role of Resting Treg cells in the development of SKCM and constructs an effective prognostic model. These findings not only enhance our understanding of the tumor immune microenvironment but also provide a new perspective for personalized treatment of SKCM. Future research is needed to further validate these results and explore the specific functions of Resting Treg cells in the tumor microenvironment.

Despite advances with anti-PD-1 therapies, such as nivolumab and pembrolizumab, many patients still experience resistance. Integration of PD-1 and CD73 pathways suggests that CD73 inhibition may enhance PD-1 blockade by targeting convergent immunosuppressive mechanisms. This supports the exploration of combination strategies to broaden the benefits of immunotherapy in CM.

P2, N=29, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

P2, N=29, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: May 2026 --> May 2031

Our study provides a spatially resolved blueprint of the melanoma TME and identifies CORO1A as a functional regulator within the immune niche, where its modulation enhances T-cell activity and synergizes with ICB. These findings reveal spatial organization as a critical determinant of immunotherapy efficacy and nominate CORO1A as a promising target for combination therapy.

Furthermore, the combination of vemurafenib with cysmethynil, a proof-of-concept ICMT inhibitor, showed efficacy in combating RAC1P29S-driven resistance of BRAFV600E melanoma cells in both in vitro and in vivo settings...We further validated the role of TAZ in RAC1P29S-driven resistance by demonstrating that introducing a constitutively-active TAZ mutant enhanced the resistance to MAPK pathway inhibitors in native cells, phenocopying the effect of RAC1P29S. The novel application of MAPK pathway inhibitors and cysmethynil combination in RAC1P29S-driven MAPK-pathway-inhibitor-resistant melanoma cells extends the potential utility of ICMT inhibitors, and also provides a new mechanism for targeting ICMT in cancer.