CDK12 (Cyclin dependent kinase 12)

This study provides a framework for selecting cell lines that are responsive to each of the 35 anticancer drugs and elucidating their underlying therapeutic mechanisms through follow-up studies. Ultimately, clinical studies are required to confirm the therapeutic efficacy of the selected drugs.

This combinatorial therapy fundamentally remodeled the tumor immune microenvironment, effectively reversing immunosuppression and activating a potent antitumor immune response. By integrating targeted chemotherapy, PTT, and immunotherapy through this unique synergistic axis, the ZCPc nanoplatform presents a potent paradigm for eliciting effective antitumor immune responses in TNBC.

P1/2, N=38, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P2, N=40, Active, not recruiting, VA Office of Research and Development | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2026

Our study revealed dynamic shifts in genetic mutations in patients with mCRPC following ARPI, PARPi and taxanes. Furthermore, our findings highlight associations between AR alterations and clinical outcomes, emphasizing the potential for personalized treatment strategies.

The patient was started on androgen deprivation therapy with goserelin (10.8 mg every 3 months) and bicalutamide (50 mg once daily), and stable disease was achieved for 66 months...Bicalutamide was replaced by enzalutamide (160 mg once daily) in the treatment regimen. Subsequently, based on the identification of CDK12 mutations by genetic testing, treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (300 mg twice daily) was initiated. To date, the patient has remained clinically stable with low PSA levels. This case highlights the potential utility of molecular profiling and combined PARP inhibition and androgen receptor-targeting therapy in CDK12-mutated metastatic castration-resistant PCa with rare penile metastasis.

This study provides the first comprehensive dataset on the spectrum of somatic HRR mutations in Indian patients with prostate cancer. The prevalence (30.5%) was somewhat higher than the global studies, ATM was the most frequently mutated gene, followed by BRCA1, in contrast to Western and Asian cohorts, where BRCA2 predominates. These findings suggest potential population-specific variations and underscore the need for broader HRR testing to better delineate the genomic landscape of prostate cancer in Indian patients.

P2, N=19, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2025 --> Apr 2026

Several phytochemicals including 2,3-Diepicastasterone from Phaseolus vulgaris (- 131.038 ± 23.572 kcal/mol), as well as compounds from Eurycoma longifolia and Oryza sativa-exhibited highly favorable binding affinities and stable interaction dynamics, highlighting them as promising scaffolds for CDK12 inhibitor development. Collectively, our findings establish CDK12 as a robust biomarker for cancer diagnosis, prognosis, and immune modulation, while highlighting natural-product-based scaffolds as promising leads for next-generation CDK12 inhibitors targeting both wild-type and resistant variants, potentially synergizing with emerging immuno-oncology strategies.

Consequently, elucidating the therapeutic mechanisms of CDK12/13 inhibition has significant translational value for precision oncology. In addition, through bioinformatics techniques, we identified new candidate targets for CDK12/13, contributing to the enrichment of the regulatory network of CDK12/13.

P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

P2, N=120, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2026 --> Dec 2029 | Trial primary completion date: Feb 2026 --> Dec 2029