Researchers are testing PMD-026, a new oral drug that blocks RSK, a protein central to cancer cell growth. High RSK levels are found in about 70% of breast cancers and are linked to poor survival and resistance to standard therapies. RSK promotes tumor growth by speeding up the cell cycle, helping cancer cells repair DNA, and allowing tumors to bypass treatments like hormone therapy and CDK4/6 inhibitors.
The Dauntless-1 trial studied PMD-026 in patients with advanced breast cancer who had already tried multiple therapies. Among patients with high RSK levels, about 70% achieved disease control, and 40% saw measurable tumor shrinkage. Progression-free survival was 4.3–4.8 months, compared with 1.3 months in patients with low RSK. Side effects, including fatigue and temporary liver enzyme increases, were generally manageable.
Researchers are now focusing on ESR1 wild-type breast cancer, which accounts for roughly 60% of cases and has limited targeted treatment options. Early lab studies show PMD-026 combined with the hormone therapy fulvestrant can reduce estrogen receptor activity by 84%. Beyond breast cancer, RSK inhibition may also be useful in other cancers, such as B-cell lymphoma, by blocking survival signals that tumors rely on. PMD-026 represents a promising new approach for resistant cancers and patients with few treatment options.