A new investigational drug, SYN818, is showing early promise in the fight against advanced cancers, with potential particular relevance for prostate cancer patients. SYN818 is an oral inhibitor of DNA polymerase theta (POLQ), a protein critical for repairing severe DNA damage. By targeting POLQ, SYN818 exploits vulnerabilities in tumors with deficiencies in homologous recombination repair (HRR) genes, such as BRCA1, BRCA2, and ATM — mutations commonly found in aggressive forms of prostate cancer.

Currently in Phase I clinical trials, SYN818 has demonstrated a favorable safety profile, with no severe adverse events reported at early dose levels. Future studies will explore combining SYN818 with PARP inhibitors, a strategy designed to intensify the selective destruction of HRR-mutated tumor cells. Given the high rate of HRR mutations in metastatic prostate cancer, researchers are hopeful that SYN818 could open new treatment avenues for patients facing resistance to existing therapies.

With further clinical results expected, SYN818 stands out as a therapy to watch for genetically defined subsets of prostate cancer and other solid tumors.

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Clinical trial.