Prognostic gene expression profile testing to inform use of adjuvant therapy: A survey of melanoma experts

Fastner, Suzanne; Shen, Nathan; Hartman, Rebecca I.; Chu, Emily Y.; Kim, Caroline C.; Kirkwood, John M.; Grossman, Douglas

doi:10.1002/cam4.6819

Cited by 3 publications

(5 citation statements)

References 11 publications

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“…For high risk of development of metastatic disease stages IIB and C, and when SLNB is positive, adjuvant postsurgical therapy can be applied with some limitations that either include immunotherapy using immune check point inhibitors (ICIs) or targeted therapy [ 30 , 48 , 191 ]. However, the majority of experts acknowledge that the serious adverse side effects may outweigh potential benefits for stage IIB/C and perhaps some IIIA patients (positive SLNB) vs. clinical observation [ 192 ]. This is in addition to the high costs of such therapies.…”

Section: Cutaneous Melanoma In a “Nutshell”mentioning

confidence: 99%

“…This is in addition to the high costs of such therapies. The attendant toxicity of immunotherapy in melanoma patients is well documented [ 48 , 191 , 192 , 193 ]. Therefore, gene profile testing (GEP) promises to help which subsets of stage IIB/C would benefit from adjuvant therapy [ 192 ].…”

Section: Cutaneous Melanoma In a “Nutshell”mentioning

confidence: 99%

“…The attendant toxicity of immunotherapy in melanoma patients is well documented [ 48 , 191 , 192 , 193 ]. Therefore, gene profile testing (GEP) promises to help which subsets of stage IIB/C would benefit from adjuvant therapy [ 192 ]. Interestingly, T-cell gene signatures derived from inflammatory skin diseases, such as systemic lupus erythematous (SLE) or psoriasis, can provide potential biomarkers for predicting the response to immune checkpoint blockade therapy in melanoma [ 194 ].…”

Section: Cutaneous Melanoma In a “Nutshell”mentioning

confidence: 99%

“…Interestingly, T-cell gene signatures derived from inflammatory skin diseases, such as systemic lupus erythematous (SLE) or psoriasis, can provide potential biomarkers for predicting the response to immune checkpoint blockade therapy in melanoma [ 194 ]. Stage III and IV melanoma patients are the subjects of immunotherapy, targeted therapy, or combined therapy [ 30 , 48 , 191 , 192 , 193 , 195 , 196 , 197 ].…”

Section: Cutaneous Melanoma In a “Nutshell”mentioning

confidence: 99%

“…The currently approved immunotherapy approaches involve targeting with antibodies the following ICIs: cytotoxic T lymphocyte-associated antigens 4 (CTLA-4), programmed cell death 1 (PD-1), PD ligand 1 (PDL-1), and lymphocyte-activation gene 3 (LAG3), with a combination of the antibodies if necessary, or in combination with other treatments [ 18 , 30 , 36 , 46 , 48 , 191 , 192 , 193 , 195 , 196 , 197 , 210 ]. They appear to be effective in a certain subset of patients [ 211 ].…”

Section: Cutaneous Melanoma In a “Nutshell”mentioning

confidence: 99%

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Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Slominski,

Kim,

Janjetovic

et al. 2024

Cancers

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Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem.

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Section: Cutaneous Melanoma In a “Nutshell”mentioning

confidence: 99%

Section: Cutaneous Melanoma In a “Nutshell”mentioning

confidence: 99%

Section: Cutaneous Melanoma In a “Nutshell”mentioning

confidence: 99%

Section: Cutaneous Melanoma In a “Nutshell”mentioning

confidence: 99%

Section: Cutaneous Melanoma In a “Nutshell”mentioning

confidence: 99%

See 3 more Smart Citations

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Slominski,

Kim,

Janjetovic

et al. 2024

Cancers

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31‐GEP (DecisionDx): a review of clinical utility and performance in a Mayo Clinic cohort

Pazhava,

Kim,

Jing

et al. 2024

Int J Dermatology

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BackgroundCutaneous melanoma (CM) is a significant health concern because of its high metastatic potential. Gene Expression Profile (GEP) testing, particularly the 31‐GEP test (DecisionDx‐Melanoma), has been increasingly used for risk stratification in CM patients. This study aimed to evaluate the clinical utility and performance of the 31‐GEP test in a real‐world setting.MethodsPatients with CM who underwent 31‐GEP testing from August 2014 to August 2022 at our institution were identified through searches of electronic health records. The study analyzed the influence of 31‐GEP testing on clinical decision‐making related to sentinel lymph node biopsy (SLNB), medical oncology referral, and postdiagnosis surveillance. Kaplan–Meier curves and Cox proportional hazard models were used to elucidate the test's performance, focusing on relapse‐free survival (RFS) and melanoma‐specific survival (MSS).ResultsThe study included 65 CM patients. Dermatologists ordered more than 80% of 31‐GEP tests. In 81.5% of cases, 31‐GEP results did not alter standard clinical management. SLNB decisions were unaffected in 92% of patients with pre‐SLNB 31‐GEP results. Among patients with stage I‐IIA melanoma, 25% of those with high‐risk 31‐GEP results were referred to medical oncology. Contrary to expectations, the rate of nodal metastasis was higher in low‐risk than in high‐risk 31‐GEP cases. Survival analysis showed overlapping RFS and MSS curves between different 31‐GEP classes, suggesting limited prognostic value.ConclusionsThe 31‐GEP test has a limited impact on clinical management decisions and shows limited prognostic value.

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Marizomib Promotes Senescence or Long-Term Apoptosis in Melanoma Cancer Cells

Piskorz,

Krętowski,

Cechowska-Pasko

2024

Molecules

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Cellular senescence is cell cycle arrest and the inhibition of cell proliferation. New anticancer approaches include the elimination of cancer cells through the induction of senescence followed by senolysis. New prosenescence compounds are still being searched for. Little is known about the ability of proteasome inhibitors to induce senescence in tumor cells, especially in malignant melanoma. The aim of our study was to verify the activity of a natural proteasome inhibitor—marizomib (MZB)—directly after incubation and after its removal to assess its potential to induce senescence or long-term apoptosis in malignant melanoma cell lines (A375 and G361). After 48 h of incubation with MZB, we observed an increased number of SA-β-galactosidase-positive cells, upregulated expression of P21 and P-P53 proteins and an increased number of cells at the subG1 phase (line G361) or at both the subG1 and G2/M phases (line A375). After 96 h from inhibitor removal, the G361 line presented signs of senescence (increased level of SA-β-galactosidase, IL-8, P-P53, G2/M and S phases of cell cycle, decreased lamin B1 and cleaved lamin B1), while the A375 line demonstrated more signs of apoptosis (increased subG1 phase, P-P53, cleaved lamin B1). The gathered findings suggest that MZB resulted in the induction of cellular senescence (line G361) or enhanced apoptosis (line A375) in the melanoma cell lines tested here and could be a promising therapeutic factor in malignant melanoma treatment.

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Prognostic gene expression profile testing to inform use of adjuvant therapy: A survey of melanoma experts

Cited by 3 publications

References 11 publications

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

31‐GEP (DecisionDx): a review of clinical utility and performance in a Mayo Clinic cohort

Marizomib Promotes Senescence or Long-Term Apoptosis in Melanoma Cancer Cells

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