Breakthrough Compounds Target Cancer-Driving Gene RAS, Enter Human Trials
A novel approach to cancer treatment, focused on disrupting the interaction between the RAS gene and a key growth pathway, is now being tested in human clinical trials. The potential therapy, developed jointly by scientists at the Francis Crick Institute and Vividion Therapeutics, offers a promising new avenue for treating a wide range of cancers while minimizing harm to healthy cells.
The RAS gene is a critical regulator of cell growth and division, but mutations in this gene are implicated in approximately 20% of all cancers. When mutated, RAS remains perpetually active, relentlessly signaling cells to proliferate. For years, directly targeting RAS has proven challenging due to the essential role of the pathways it controls in normal cellular function. Blocking these pathways entirely can lead to debilitating side effects, such as hyperglycemia, as one key enzyme, PI3K, is also involved in insulin regulation.
Published October 9 in the journal Science, the research details a strategy to selectively disrupt the RAS-PI3K interaction. Researchers employed a combination of chemical screening and biological testing to identify compounds that effectively block this connection without interfering with PI3K’s other vital functions.
“Given the RAS gene is mutated across a wide range of cancers, we’ve been exploring how to stop it interacting with cell growth pathways for many years, but side effects have held back the development of treatments,” explained a senior researcher at the Crick Institute. “Our collaborative effort has overcome this challenge by targeting the PI3K and RAS interaction specifically, leaving PI3K free to bind with its other targets.”
Vividion Therapeutics researchers pinpointed small molecules that bind to the surface of PI3K, preventing RAS from attaching. Using an assay developed by the Crick team, they confirmed that these compounds successfully blocked the RAS-PI3K interaction while preserving PI3K’s role in insulin signaling. Initial testing in mice with RAS-mutated lung tumors demonstrated that the treatment halted tumor growth without elevating blood sugar levels.
Further studies revealed synergistic effects when the new compound was combined with existing drugs targeting other enzymes within the same pathway. This combination therapy resulted in more potent and sustained tumor suppression. Notably, the compound also proved effective in mice with tumors driven by HER2 mutations – a gene frequently overactive in breast cancer – even without directly impacting RAS. This suggests the treatment could have broad applicability across various cancer types.
The drug has now advanced to Phase 1 clinical trials, evaluating its safety and potential side effects in patients with both RAS and HER2 mutations. The trial will also assess the efficacy of combining the new compound with other RAS-targeting therapies.
“This discovery is a great example of how new discovery approaches can open up completely novel ways to tackle cancer,” stated a company representative from Vividion. “By designing molecules that stop RAS and PI3K from connecting, while still allowing healthy cell processes to continue, we’ve found a way to selectively block a key cancer growth signal. It’s incredibly rewarding to see this science now progressing in the clinic, where it has the potential to make a real difference for patients.”
The success of this collaborative effort highlights the power of integrating fundamental biological understanding with advanced chemical innovation, offering renewed hope in the ongoing fight against cancer.
