Imagine if cancer cells could be tricked into self-destructing—that’s exactly what Stanford researchers are making possible. They’ve crafted a revolutionary compound that flips the genetic switch inside cancer cells, triggering them to initiate their own demise.¹
Published in Science, this breakthrough could lead to therapies that enlist the body’s own defenses to eliminate tumors, offering a new frontier in cancer treatment.
How Your Body’s Natural Processes Could Help Stop Tumor Growth
Apoptosis is the process where cells are genetically programmed to die. It happens in multicellular organisms and even some single-celled ones. You might also hear it called “programmed cell death” or “cell suicide.” (ref) This constant turnover helps replace old or damaged cells with fresh, new ones.
In cancer, however, cells stop following these natural signals and instead keep growing. Many cancers rely on specific proteins, called kinases, to send signals that drive this unchecked growth and survival.
Kinases act as major communication hubs within cells, sending and amplifying signals from the cell’s outer membrane to its nucleus. When these kinases mutate or are overactive, they can lead to dangerous, uncontrolled cell proliferation.
Because of their central role in cancer growth, kinases have become key targets in cancer treatment. Researchers have already developed drugs to block kinase activity, with many of these drugs proving effective in clinical treatments.
Building on these successes, researchers at Stanford Medicine are now taking it a step further by using apoptosis to make cancer cells “dispose of themselves.”
New Molecules Zero In on BCL6 to Stop Lymphoma
The researchers developed specialized molecules, called CDK-TCIPs, to target and destroy cells in diffuse large B cell lymphoma, a cancer driven by overexpression of the BCL6 transcription factor.
The strongest CDK-TCIPs destroyed lymphoma cells at extremely low doses, up to 100 times more effective than other small-molecule inhibitors, while being 200 times less toxic to normal cells.
Here’s a breakdown of how it works:
- What CDK-TCIPs Do: CDK-TCIPs are special molecules that target BCL6, a protein that can help some cancer cells (like in certain lymphomas) grow and survive by silencing genes that usually tell the cell to die. The CDK-TCIPs work by bringing CDK9 (a kinase that’s involved in activating certain genes) to DNA sections bound by BCL6. This disrupts BCL6’s normal function, reactivating the cell death genes BCL6 had been suppressing.
- Effect on Cancer Cells: By turning these “death” genes back on, CDK-TCIPs specifically kill lymphoma cells that rely on BCL6 for their survival. Tests showed that one of the CDK-TCIPs was highly effective at targeting these cancer cells, even among hundreds of different cancer cell types.
- Expanding the Approach: The researchers discovered they could use this approach with other kinases, like CDK12 and CDK13, to achieve similar cancer-killing effects, still focused on BCL6.
- Potential for Broader Use: In mouse models, they used CDK-TCIPs to selectively kill only the harmful B cells that depend on BCL6 and leaving healthy cells alone. This precision could lead to safer treatments for cancer and even autoimmune diseases by targeting only harmful cells without affecting the rest.
So, essentially, CDK-TCIPs represent a new, highly targeted way to fight cancers that rely on BCL6, with a good chance of minimal impact on healthy cells.
Targeting Other Types of Cancer in the Future
This approach could also prevent cancer from relapsing by targeting multiple cancer-causing pathways at once. The team hopes these molecules might lead to effective therapies against other cancer-driving proteins, including the Ras oncogene, which drives several cancer types.
As Sai Gourisankar, PhD, one of the study’s authors, described it, “It’s sort of cell death by committee. And once a cancer cell is dead, that’s a terminal state.”
Gerald Crabtree, MD, a cancer biologist and one of the study’s authors, first thought of the cancer cell self-destruction concept while walking through Kings Mountain’s forests near Palo Alto, California. Now, he and his colleague, Nathanael Gray, PhD, have co-founded Shenandoah Therapeutics to advance this promising treatment and gather data for future clinical trials. (ref)
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Nancy Maffia
Nancy received a bachelor’s in biology from Elmira College and a master’s degree in horticulture and communications from the University of Kentucky. Worked in plant taxonomy at the University of Florida and the L. H. Bailey Hortorium at Cornell University, and wrote and edited gardening books at Rodale Press in Emmaus, PA. Her interests are plant identification, gardening, hiking, and reading.
