MY LATEST PUBLICATIONS
CDK7-targeted therapy effectively disrupts cell cycle progression and oncogenic signaling in head and neck cancer
Signal Transduct Target Ther 2025 Nov 6;10(1):363.
https://doi.org/10.1038/s41392-025-02452-z
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Head and neck squamous cell carcinoma (HNSCC) remains a prevalent and aggressive malignancy, characterized by a lack of targeted therapies and limited clinical benefits. Here, we conducted an optimized whole-genome CRISPR screen across five HNSCC cell lines aimed at identifying actionable genetic vulnerabilities for rapid preclinical evaluation as novel targeted therapies. Given their critical role in cancer, cyclin-dependent kinases (CDKs) were prioritized for further investigation. Among these, CDK7 was identified as an essential and targetable gene across all five cell lines, prompting its selection for in-depth functional and molecular characterization. Genetic and pharmacological inhibition of CDK7 significantly and consistently reduced tumor cell proliferation due to generalized cell cycle arrest and apoptosis induction. Additionally, CDK7 knockout (KO) and selective inhibitors (YKL-5-124 and samuraciclib) demonstrated potent antitumor activity, effectively suppressing tumor growth in HNSCC patient-derived organoids (PDOs), as well as in both cell line- and patient-derived xenograft (PDX) mouse models with minimal toxicity. Mechanistically, CDK7 inhibition led to a broad downregulation of gene sets related to cell cycle progression and DNA repair, and significantly reduced the transcription of essential genes and untargetable vulnerabilities identified by our CRISPR screen. These findings highlight CDK7 as a promising therapeutic target for HNSCC. Our study provides strong evidence of the robust antitumor activity of CDK7-selective inhibition in disease-relevant preclinical models, strongly supporting its progression to clinical testing.​
Lentiviral-mediated panErbB CAR-T cell therapy against head and neck squamous cell carcinomas for patients with Fanconi anemia
Mol Ther Oncol 2025 Sep 22;33(4):201060
https://doi.org/10.1016/j.omton.2025.201060
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Fanconi anemia (FA) is a DNA repair syndrome characterized by bone marrow failure and cancer predisposition, including acute myeloid leukemia and solid tumors such as head and neck squamous cell carcinoma (HNSCC). Due to the exacerbated toxicity of radio-chemotherapy in FA patients with HNSCC, there is an urgent need of safer and more efficient antitumoral therapies for these patients, such as those based on chimeric antigen receptor (CAR)-T cells. Here, we show that HNSCC cell lines from both the general population and patients with FA express ErbB family members, which can be recognized by the T1E panErbB ligand. The generation of a lentiviral vector encoding for a second-generation T1E-CAR allowed us to generate panErbB CAR-T cells from healthy donors (HDs) and patients with FA. Despite the molecular and cellular defects characteristic of FA cells, a similar efficacy of CAR-T generation was observed, regardless of the donor origin. In all cases, panErbB CAR-T cells exerted potent cytotoxicity against all HNSCC cell lines tested in vitro. In addition, intratumoral administration of these CAR-T cells in HNSCC xenografts markedly reduced tumor growth. These preclinical results suggest that panErbB CAR-T cells would represent a safe, non-genotoxic therapy for HNSCC, with particular applicability for patients with FA.
