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These melanogenesis studies established MT-1 as the most pharmacologically tractable reference agonist for MC1R-mediated pigmentation biology and provided the foundational characterisation of the MC1R-cAMP-MITF-tyrosinase signalling cascade

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Importantly, a randomized controlled trial demonstrated that L-carnitine supplementation reduces the intramyocellular-to-extramyocellular lipid ratio in NAFLD patients, suggesting enhanced clearance and utilization of intracellular lipid stores in skeletal muscle independent of weight changes (41)

Key Points The discovery of androgen dependence in prostate cancer in 1941 by Huggins and colleagues still remains the backbone for the treatment of advance-staged prostate cancer Over the past decade, the better understanding of the mechanisms driving resistance to castration has led to development of abiraterone acetate and enzalutamide, two next-generation androgen receptor (AR) targeting agents Several challenges remain including resistance to continued blocking of the AR axis, cross-resistance between agents, ideal sequence of administration, combination strategies, and coordination with other treatments Molecular characterization of patients, through next-generation sequencing or transcriptome analysis, will help to dissect mechanisms of resistance and to identify biomarkers allowing the selection of patients for specific treatment The improved understanding of intra-patient molecular heterogeneity and of the multiple, redundant and compensatory signalling networks in cancers supports a role for rational combinatorial, targeted therapeutic approaches Abstract The discovery of androgen dependence in prostate cancer in 1941 by Huggins and colleagues has remained the backbone for the treatment of this disease