Two Cancer Drug Advances Show Promise in Early Research

Two separate cancer drug developments have shown early promise in recent research, targeting different mechanisms to improve treatment outcomes.

An early-stage clinical trial of Rezatapopt, a new drug targeting a specific mutation in the p53 gene, demonstrated a 20% response rate in patients with advanced cancers. P53 is mutated in around 70% of all cancers, making it an attractive therapeutic target, though it has proven difficult to develop drugs against due to the many different mutations affecting this master regulator of cell survival. The trial showed at least 30% tumor shrinkage in responding patients across a wide range of cancer types. All patients enrolled had undergone many different therapies before entering the trial, representing the most resistant and difficult cases with highly advanced cancers. Rezatapopt can be taken orally, allowing patients to take it at home. A larger trial is underway to test whether the treatment can cure patients of their cancer.

In separate research published in the journal Gastroenterology, a team identified why immunotherapy has largely failed against fibrolamellar carcinoma, a rare and aggressive liver tumor. The study found that fibrolamellar tumors reshape the tissue around them into an immune "no entry" zone, keeping tumor-fighting T cells penned in at the edges through a process called T-cell exclusion. This immune bottleneck explains why immune checkpoint inhibition has not delivered results in this cancer type.

Fibrolamellar carcinoma tends to strike children and young adults, often in people without underlying liver disease, and makes up only a small fraction of liver cancers (up to 2%). Because it is rare and can be hard to recognize early, it is frequently discovered after it has spread, leaving patients with limited options.

The researchers tested AMD3100, an FDA-approved drug currently used to treat a different disorder, on slices of tumors obtained from patients. AMD3100 enabled T cells to enter the tumor core. When paired with immune checkpoint inhibitors, the drug further boosted T cell activity and led to a marked increase in tumor cell death.

Immune checkpoint inhibitors are designed to stimulate the body's T cells so they can move into the center of a tumor and destroy cancer cells. These drugs have been highly effective in treating several cancers, including those of the liver, lung, kidney, and bladder, as well as melanoma. However, other cancers, such as pancreatic, prostate, and brain tumors, often do not respond. The structure of the tumor microenvironment and the trapping of T cells help explain why some cancers resist this type of therapy.

Researchers are currently searching for liver cancer clinicians interested in starting clinical trials for the AMD3100 combination treatment. The fact that AMD3100 is already FDA-approved could reduce risks and potentially speed up timelines for clinical trials in fibrolamellar carcinoma.