Melanoma and MAPK Pathways

BRAF V600 and ErbB inhibitors directly activate GCN2 in an off-target manner to limit cancer cell proliferation

The paper identifies off-target activation of GCN2 by BRAF and EGFR inhibitors, showing it limits cancer cell proliferation.

Specific SOX10 enhancer elements modulate phenotype plasticity and drug resistance in melanoma

This study identifies SOX10 enhancer elements in melanoma that drive phenotype plasticity and drug resistance by modulating SOX10 expression and NTRK1 upregulation.

ARID1A-induced transcriptional reprogramming rewires signalling responses to drug treatment in melanoma

This study reveals how ARID1A-mediated transcriptional rewiring drives resistance to MAPK inhibitors in melanoma by altering signalling pathways, immune interactions, and receptor dynamics, highlighting potential targets for combinatorial therapies.

Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment

This study shows that dual FGFR/VEGFR inhibition causes regression of acral melanoma by targeting the tumor microenvironment rather than directly killing cancer cells.

Metabolism-oriented compound screen in physiological culture conditions identifies a NAMPT inhibitor highly effective against drug-naive and -resistant melanoma cells

The paper identifies FK866, a NAMPT inhibitor, as effective against drug-naive and -resistant melanoma cells in various culture conditions without affecting healthy cells.

BMP-dependent oligoclonal cancer attractor state precedes neural crest fate in melanoma initiation

The paper identifies a BMP-dependent attractor state in melanoma precursor cells that precedes neural crest fate and is associated with ID1 expression in human melanoma.

ERK hyperactivation in epidermal keratinocytes impairs intercellular adhesion and drives Grover disease pathology

This study shows ERK hyperactivation in keratinocytes causes impaired adhesion and drives Grover disease, supporting MEK inhibition as a potential therapy.

Ancestry and somatic profile predict acral melanoma origin and prognosis

This study analyzes acral melanoma genomes and transcriptomes from Mexican patients, finding ancestry-related mutation patterns and survival differences.

Human melanoma cell lines that possess wild-type BRAF alleles but are dependent on ERBB4 and ERBB2

This study investigates the role of ERBB4 heterodimers in driving the proliferation of BRAF-WT&RAS/NF1-mutant melanoma cell lines and shows that dominant-negative mutants of ERBB2 and EGFR inhibit clonogenic growth in some but not all cell lines.

Computational modeling of drug response identifies mutant-specific constraints for dosing panRAF and MEK inhibitors in melanoma

This study uses computational modeling and preclinical data to identify optimal dosing strategies for panRAF and MEK inhibitors in melanoma, revealing distinct dose requirements based on NRAS vs BRAF mutations.

Pharmacological Modulation of TRIB2 Stability in Melanoma Reveals CDK12/13 as Dominant Regulators and Potential Therapeutic Targets

This study identifies CDK12/13 as key regulators of TRIB2 stability in melanoma and presents three classes of compounds that effectively eliminate TRIB2 with higher potency than afatinib.

Mechanistic model of MAPK signaling reveals how allostery and rewiring contribute to drug resistance

The paper models MAPK signaling in BRAFV600E melanoma cells to show how allostery and rewiring lead to drug resistance.

DNA replication during acute MEK inhibition drives acquisition of resistance through amplification of the BRAF oncogene

The paper shows that DNA replication during MEK inhibition drives BRAF amplification and resistance in COLO205 cells, and that blocking cell cycle entry can suppress resistance.

Proteasomal downregulation of the pro-apoptotic MST2 pathway contributes to BRAF inhibitor resistance in melanoma

AP-1 transcription factor network explains diverse patterns of cellular plasticity in melanoma cells

The paper shows that the AP-1 transcription factor network explains cellular plasticity in melanoma by regulating differentiation states and responses to MAPK inhibitors.

Proteogenomics analysis to identify acquired resistance-specific alterations in melanoma PDXs on MAPKi therapy

The paper presents a proteogenomic approach to identify resistance-specific alterations in melanoma PDX models treated with MAPK inhibitors using custom curated databases.

Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord reproducibly models early events in ERK-mediated tumorigenesis

The paper shows sustained ERK1/2 activation in chicken embryos induces neoplasia in the spinal cord, mimicking early ERK-mediated tumorigenesis.

Novel MAPK/AKT-impairing germline NRAS variant identified in a melanoma-prone family

The paper identifies a novel NRAS variant in a melanoma-prone family and shows it impairs MAPK/AKT signaling while enhancing PI3K signaling.

Overcoming Resistance to BRAFV600E Inhibition in Melanoma by Deciphering and Targeting Personalized Protein Network Alterations

This study develops personalized drug combinations for BRAFV600E melanoma by analyzing patient-specific signaling networks, showing improved efficacy compared to standard therapies.

Epigenetic modulation reveals differentiation state specificity of oncogene addiction

The paper identifies epigenetic inhibitors that target specific differentiation states in melanoma cells, improving MAPK inhibitor efficacy based on tumor cell differentiation and MAPK activity.

Integrated Molecular Characterisation of the MAPK Pathways in Human Cancers

The paper identifies cancer-associated mutations in MAPK pathway genes across 40,848 tumors and links them to poor outcomes and drug responses.

Hotspot KRAS mutations in brain metastases at the first metastatic recurrence of cutaneous melanoma

This study identifies hotspot KRAS mutations as enriched in early brain metastases of melanoma, associated with worse survival and clonal origin, suggesting potential for risk stratification.

Disruption of Redox Balance Enhances the Effects of BRAF-inhibition in Melanoma Cells

The paper shows that increased antioxidant capacity in BRAF-mutated melanoma cells reduces sensitivity to BRAF inhibitors and suggests targeting redox pathways could improve treatment outcomes.

Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma

The paper establishes an in vitro model of MAPK inhibitor resistance in melanoma and identifies transcriptional changes and pathways involved in resistance mechanisms.