New Drug Combination Shows Promise for Prostate Cancer Treatment in Preclinical Study
A next-generation treatment strategy combining a targeted radiopharmaceutical with a kinase inhibitor has shown significant potential in combating prostate cancer, according to results from a new preclinical study.
Highlights include:
- Drug-drug synergy can add to the spectrum of available prostate cancer treatments
- Cobimetinib and [177Lu]Lu-rhPSMA-10.1 showed synergistic potency in an in vitro screen.
- The drug combination showed therapeutic efficacy in prostate cancer xenografts.
- Preclinical synergistic potency supported clinical investigation in prostate cancer.
Researchers evaluated the novel pairing of [¹⁷⁷Lu]Lu-rhPSMA-10.1, a radioligand that targets prostate-specific membrane antigen (PSMA), and cobimetinib, a drug that blocks a key cancer-driving pathway. The study found that the two agents, when used together, worked synergistically to slow tumor growth and improve survival in laboratory models of prostate cancer.
“This combination could offer a powerful new avenue for treating advanced PSMA-expressing prostate cancer,” said the study’s lead investigator. “The preclinical data are compelling and justify further clinical development.”
The study included screening 177 different anticancer drugs to identify those that might boost the effects of [¹⁷⁷Lu]Lu-rhPSMA-10.1. The researchers used 22Rv1 prostate cancer cells and a series of assays to pinpoint drugs that worked more effectively when combined with the radioligand.
Cobimetinib, a known MEK inhibitor, emerged as a top candidate. Further testing showed that the combination significantly outperformed either treatment on its own.
In models bearing human prostate tumors, the dual treatment:
- Reduced tumor size more effectively than either monotherapy (statistically significant by day 30),
- Extended median survival to 49 days, compared with 36 days for [¹⁷⁷Lu]Lu-rhPSMA-10.1 alone and 23 days for untreated animals,
- Showed no major toxic effects, even with prolonged dosing.
While these findings are limited to laboratory and animal models, the research provides strong rationale for advancing this drug pairing to clinical trials.
“With prostate cancer being the second most common cancer in men worldwide, innovative combination therapies like this are urgently needed,” the authors noted.
If future clinical studies replicate these results, this combination could represent a major step forward in precision oncology for prostate cancer patients.