New Cancer Drug Blocks Tumors Without Debilitating Side Effects

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A new cancer drug candidate, developed through a collaboration between Lawrence Livermore National Laboratory (LLNL), BridgeBio Oncology Therapeutics (BBOT), and the Frederick National Laboratory for Cancer Research (FNLCR), has shown the ability to inhibit tumor growth without causing a major side effect often seen in similar therapies.

This compound, named BBO-10203, has demonstrated early success in clinical trials by interrupting a crucial interaction between two cancer-promoting proteins, RAS and PI3Kα. Unlike previous drugs targeting this pathway, BBO-10203 does not induce hyperglycemia (elevated blood sugar levels), a complication that has previously limited treatment options. The research, published in Science, represents a significant advance for patients facing aggressive cancers that have been difficult to treat.

The development of BBO-10203 combines the power of Department of Energy (DOE) high-performance computing with artificial intelligence and biomedical innovation. At the core of the effort is LLNL’s Livermore Computer-Aided Drug Design (LCADD) platform, which integrates machine learning, AI, and physics-based simulations. This system, supported by DOE supercomputers such as Ruby and Lassen, allows scientists to model and evaluate drug behavior before any physical compound is created.

“This is a precise, targeted strike on a long-standing cancer vulnerability,” said LLNL Biochemical and Biophysical Systems Group Leader Felice Lightstone, co-author of the study. “What’s especially exciting is that this was achieved using a computational pipeline, reducing what traditionally takes many years.”

A “breaker” disrupting the RAS-PI3Kα pathway

BBO-10203 functions by interrupting the connection between two proteins commonly involved in promoting cancer growth. These proteins, which belong to the RAS and PI3K signaling pathways, are often mutated in cancer and have proven extremely difficult to target with precision and safety. According to the research team, what sets BBO-10203 apart is its ability to shut down the cancer-related signaling without disrupting normal blood sugar regulation—a side effect that has limited the success of similar drugs.

In laboratory experiments and preclinical animal studies, BBO-10203 was shown to inhibit tumor growth in multiple cancer types, including those characterized by HER2 overexpression, PIK3CA mutations, and KRAS mutations. The compound also boosted the performance of existing treatments for breast, lung, and colorectal cancers, indicating potential for use in combination therapies to enhance patient outcomes.

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