Squamous Cell Skin Cancer

P3, N=290, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Recruiting --> Active, not recruiting

P1, N=40, Recruiting, Emory University | N=12 --> 40 | Trial completion date: Jan 2027 --> Dec 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

Indeed, our de novo somatic indel calling from TCGA RNA-seq increases the TCGA driver indel repertoire by ~ 14%, especially in samples with purity < 0.4, including actionable EGFR indels in lung adenocarcinoma and FLT3 in acute myeloid leukemia. Our study not only reveals confounders in somatic mutant ASE analysis but also demonstrates their utility in RNA-based mutation calling.

P2/3, N=1714, Suspended, NRG Oncology | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

Mechanistically, our studies revealed that PLOD2 acts as a key downstream effector of STAT3 to activate ERK and AKT signaling evidenced by rescue experiments. As a result, our study not only establishes the STAT3/PLOD2/ERK-AKT axis as a key driver of cSCC but also identifies the clinically approved drug minoxidil as a potent PLOD2 inhibitor, demonstrating immediate promise as a repurposed therapeutic agent.

In vivo, using a DMBA/croton oil-induced cSCC mouse model, DOE administration resulted in dose-dependent tumor inhibition and improved body weight loss, thymus, and spleen indices. DOE, as a flavonoid extract, significantly inhibits cell proliferation, migration, and promotes apoptosis in cSCC, positioning it as a promising candidate for further development as a complementary or adjuvant therapeutic strategy.

P1/2, N=90, Recruiting, Replimune Inc. | N=65 --> 90 | Trial completion date: Jan 2028 --> Nov 2029 | Trial primary completion date: Sep 2027 --> Jul 2029

Amphiregulin emerges as a dominant functional mediator, and its depletion phenocopies key aspects of p63/p73 loss, including impaired proliferation and tumor formation. Together, these findings support a model in which shared enhancer occupancy by p63 and p73 drives cooperative and factor-specific transcriptional programs, linking chromatin regulation to signaling and tumor maintenance.

Our results suggest that BNs are a valuable tool for representing complex clinical decision-making processes.

This large, multi-institutional genomic analysis defines recurrent mutational and structural alterations in cSCC and highlights an integrated pattern of pathway disruption involving genomic integrity, differentiation, epigenetic control, and proliferative signaling. These findings enhance current understandings of the molecular architecture underlying this common yet genomically understudied malignancy and provide a foundation for future mechanistic studies and development of targeted diagnostic and therapeutic strategies.

Our findings provide a basis for improved high-risk patient stratification by highlighting a TrkB-based signature and generating prototype predictive models. Furthermore, they offer promising therapeutic avenues for developing combined targeted interventions to overcome resistance in high-risk patients.

P2, N=63, Active, not recruiting, Incyte Corporation | Trial completion date: Dec 2026 --> Sep 2026 | Trial primary completion date: Dec 2025 --> Sep 2026