Phase 1 Trial for DCC-2812 in Metastatic Castration-Resistant Prostate Cancer

DCC-2812 is a new oral drug designed to fight advanced cancers, especially in the urinary and reproductive systems like kidney, bladder, and prostate cancers. It works by turning on a special stress response inside cancer cells that pushes them past their breaking point, leading to cell death. Cancer cells live in harsh environments with low nutrients and oxygen, so they rely on a backup system called the integrated stress response (ISR) to survive.

This response helps them slow down normal protein production and make protective proteins instead. DCC-2812 targets a key switch in this system called the GCN2 kinase, activating it strongly to overload the stress response and trigger apoptosis, or programmed cell death. Unlike most drugs that block enzymes, this one activates the GCN2 enzyme through a clever allosteric binding. It latches onto one part of the enzyme pair, boosting activity in the other part, which then adds a phosphate tag to a protein called eIF2α. This tag slams the brakes on most protein-making while ramping up production of ATF4, a master regulator that turns on genes for handling extreme stress.

In lab tests on cancer models, DCC-2812 slowed tumor growth by up to 92% on its own and worked even better with standard treatments like blood vessel blockers or other targeted drugs, causing tumors to shrink or disappear completely in some cases. The drug has good properties for oral use, like strong absorption, tissue penetration, and staying power in the body without hitting other enzymes off-target.

Right now, it’s in early human testing for people with advanced kidney cell cancer, bladder cancer, and prostate cancer that resists hormone therapy. Early lab work showed it shines in stressed tumors, like those in the kidney, by making cells unable to cope with their own chaos. This approach flips the script on cancer’s survival tricks, potentially opening doors for combining it with therapies that add even more stress, like cutting off blood supply or blocking growth signals.

Clinical trial.