Prostate cancer is the second most common cancer worldwide, leading to more than one million diagnoses per year. Metastatic prostate cancer is commonly treated with hormone therapy. These cancer cells need activation of the androgen receptor to divide, so drugs that drop testosterone levels block tumor growth. Unfortunately, resistance to hormone therapy tends to develop in one to two years.
Resistance often involves cancer cells reactivating the androgen receptor without needing testosterone. The authors of a recent study were interested in finding a way to re-inactivate it. The protein CDK7 is an attractive drug target because it is involved in both androgen receptor regulation and cell cycle regulation. The drug CT7001 inhibits CDK7, and shows promising experimental results in several other cancers. Therefore, these authors tested the effectiveness of CT7001 in prostate cancer.
They found that in prostate cancer cell lines, CT7001 binds to CDK7. This molecule also inhibits the androgen receptor, inhibits cell growth, and causes cell cycle arrest. The authors then treated mice carrying prostate cancer tumors with CT7001, or enzalutamide (a drug that blocks testosterone), or both. CT7001 shrank tumors, and the combination of CT7001 and enzalutamide worked even better.
The in vitro and mouse evidence from this study suggests that this chemical could help fight this disease, especially in combination with hormone therapy drugs.
Constantin T, Varela-Carver A, Greenland K, et al. The CDK7 inhibitor CT7001 (samuraciclib) targets proliferation pathways to inhibit advanced prostate cancer. Br J Cancer. 2023 Jun;128(12):2326-2337. PMID: 37076563. doi: 10.1038/s41416-023-02252-8