Innovative Approach to Cancer Treatment: Enzyme Blockade Rewires Tumor Cells

Recent research has identified a novel strategy to combat cancer by targeting a critical enzyme involved in protein synthesis. Scientists at Johns Hopkins University School of Medicine have demonstrated that inhibiting RNA Polymerase 1 (Pol 1), the enzyme responsible for producing ribosomal RNA (rRNA), can effectively disrupt cancer cell growth. Their studies reveal that blocking this enzyme triggers a unique stress response within tumor cells, leading to alterations in RNA splicing—the process in which cells modify RNA to produce different proteins. This rewiring of RNA splicing hinders tumor proliferation and could open new avenues for therapies against resistant cancers.

The research highlights the dual role of the ribosomal protein RPL22, traditionally known for its structural function, as a regulator of RNA splicing. By using specific drugs such as BMH-21 and a novel compound called BOB-42, the team found that tumors harboring mutations in RPL22 or elevated levels of proteins like MDM4 and RPL22L1 are more sensitive to Pol 1 inhibition. These genetic alterations are commonly seen in mismatch repair-deficient cancers, including colorectal, stomach, and uterine cancers.

Experimental treatments showed promising results in animal models, with tumor sizes reducing by up to 77%. These findings suggest that targeting rRNA synthesis not only suppresses tumor growth but may also enhance the effectiveness of immune-based therapies. The researchers propose that manipulating RNA splicing in cancer cells could improve immune recognition and response.

This breakthrough emphasizes that ribosome biogenesis is a hallmark of cancer and that disrupting this process holds potential for developing targeted treatments. The study underscores a new conceptual framework, where inhibiting components of protein synthesis machinery impacts tumor behavior and immune interactions, offering hope for patients with treatment-resistant cancers.