Phase 1 Trial Investigates MAO-A Inhibition With ITR-251 to Overcome Prostate Cancer Resistance

A new Phase 1 clinical trial  will investigate ITR-251, an experimental inhibitor of monoamine oxidase A (MAO-A), as a potential treatment for advanced solid tumours and metastatic castration-resistant prostate cancer (mCRPC).

What makes this investigation unusual is its molecular target.

MAO-A is an enzyme best known for breaking down neurotransmitters and other monoamines. However, research has also implicated MAO-A in biological processes associated with tumour progression, cellular adaptation and resistance to treatment.

In prostate cancer, laboratory investigations suggest that MAO-A may contribute to mechanisms that help malignant cells survive despite androgen suppression. Inhibiting this enzyme could therefore provide a way to interfere with cancer survival pathways without directly targeting the androgen receptor itself.

This is particularly relevant to mCRPC, where tumour cells can develop ways to survive and proliferate despite continued suppression of testosterone and treatment with modern antiandrogen therapies.

The first stage of the trial will evaluate ITR-251 alone, primarily to establish its safety, tolerability and recommended dose. A subsequent stage will investigate ITR-251 alongside continued ADT and an ARPI in patients with mCRPC.

Researchers will assess adverse events, dose-limiting toxicities and the pharmacological characteristics of the treatment. Evidence of antitumour activity will also be explored, although demonstrating clinical efficacy is not the primary purpose of this early-stage investigation.

The planned combination with hormonal therapy introduces another important question: whether MAO-A inhibition can provide an additional benefit beyond that achieved with androgen receptor pathway suppression alone.

Clinical trial.