The following is a summary of “Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes,” published in the December 2024 issue of Dermatology by Pla et al.
The use of PD1 and CTLA4 inhibitors has transformed malignant melanoma (MM) treatment, but resistance to targeted and immune-checkpoint therapies remains a significant challenge.
Researchers conducted a retrospective study to mine large-scale MM proteogenomic data to identify druggable targets and predict treatment efficacy and resistance.
They analyzed protein profiles from established MM subtypes and the molecular structures of 82 cancer treatment drugs to identify 9 candidate hub proteins: mTOR, FYN, PIK3CB, EGFR, MAPK3, MAP4K1, MAP2K1, SRC, and AKT1, which spanned 5 MM subtypes. These proteins were considered potential drug targets for 1 or more MM subtypes. Additionally, they integrated proteogenomic profiles from MM subtypes with MM cell line dependency and drug sensitivity data, identifying 162 potentially targetable genes. Finally, 20 compounds were found to have potential drug impact in at least 1 MM subtype.
The results showed that employing unbiased approaches revealed compounds targeting ferroptosis, exhibiting a remarkable 30-fold difference in sensitivity across different MM subtypes.
Investigators concluded that proteomic profiling of melanoma samples suggests innovative and novel therapeutic strategies through stratification of patients, offering a spectrum of novel therapeutic interventions and the potential for combination therapies.
Source: onlinelibrary.wiley.com/doi/full/10.1111/ijd.17586
