Certain genes have the potential to mutate into oncogenes, which can drive the development of cancer by promoting uncontrolled cell proliferation and blocking the normal process of apoptosis (cell death). For years, cancer treatments have focused on shutting down these rogue genes and the proteins they produce. However, a new study from researchers at Stanford University takes a completely different approach—one that aims to harness the power of oncogenes to treat cancer.

“Since oncogenes were discovered, people have been trying to shut them down in cancer,” said Roman Sarott, co-first author of the study. “Instead, we’re trying to use them to turn signaling on that, we hope, will prove beneficial for treatment.” This innovative strategy targets a specific oncogene protein called BCL6, which is known to play a key role in diffuse large B-cell lymphoma (DLBCL), a type of blood cancer. In its mutated form, BCL6 binds to DNA near genes that would normally trigger apoptosis, effectively turning them off and allowing cancer cells to continue dividing uncontrollably.

To counter this, the researchers developed a molecular “glue” that binds BCL6 to another protein called CDK9. While BCL6 suppresses apoptosis genes, CDK9 is known to activate them. By linking these two proteins together, the researchers were able to “flip the switch” and reactivate the apoptosis genes that BCL6 was silencing, leading to the targeted death of lymphoma cells in lab tests.

“The idea is, Can you turn a cancer dependency into a cancer-killing signal?” explained Nathanael Gray, co-senior author of the study. “You take something that the cancer is addicted to for its survival and you flip the script and make that be the very thing that kills it.” This groundbreaking approach aims to make the very protein that cancer cells rely on for survival become their undoing.

Importantly, this method appears to be highly selective for DLBCL. In tests conducted in mice without cancer, the researchers observed no significant negative side effects, although some healthy immune cells were also affected. Unlike traditional treatments like chemotherapy or radiation, which indiscriminately damage both cancerous and healthy cells, this new approach seems to spare healthy tissue, making it a potentially much more targeted and less harmful option.

In another experiment, the team tested the molecular glue on 859 different types of cancer, and the only one it effectively targeted was diffuse large B-cell lymphoma. The researchers are optimistic that this technique could be adapted to target other cancer-causing proteins, such as Ras, which is implicated in a range of cancers.

While this is a promising new mechanism, it’s still in its early stages. The team is currently conducting further tests in mice with DLBCL, hoping that this novel approach can be refined and eventually applied to a broader range of cancers with extreme precision.

If successful, this strategy could pave the way for a new class of cancer treatments that avoid the widespread damage caused by traditional therapies, offering a more focused and less toxic alternative for cancer patients.

By Impact Lab