Radiation therapy has long been a staple in the fight against tumors, yet its broad-spectrum approach often harms nearby healthy tissues.
A team of researchers at UCSF is changing the game by introducing a method that precisely targets cancer cells, dramatically improving treatment effectiveness while reducing adverse side effects.
This Cutting-Edge Therapy
This cutting-edge therapy combines a special drug that tags cancer cells for destruction with a radioactive antibody specifically designed to eliminate these marked cells.
In studies conducted on mice, this innovative technique successfully eradicated bladder and lung tumors, all while sparing the animals from the usual fatigue and weight loss commonly associated with radiation treatments.
Dr. Charly Craik, a pharmaceutical chemistry professor at UCSF, describes this method as a significant leap forward.
It harnesses the power of dual action against tumors, potentially thwarting the cancer’s ability to develop resistance.
Foundation and Development
The roots of this project trace back more than ten years. Dr. Kevan Shokat, another prominent UCSF researcher, uncovered a way to inhibit KRAS—a protein whose mutations are notorious for driving cell proliferation across various cancers.
With KRAS mutations implicated in nearly 30% of all cancer cases, this discovery was pivotal.
Building on Shokat’s work, the team developed several drugs targeting oncogenic KRAS.
These drugs initially reduced tumor size, but the cancer often made a quick comeback. Dr. Craik speculated that by remaining attached to KRAS, these drugs could make cancer cells more visible to the immune system.
In a collaborative effort in 2022, Craik and Shokat’s team confirmed this theory.
They engineered an antibody that could identify a specific fragment of the drug-bound KRAS on cancer cell surfaces, prompting an immune response.
However, the immune system was not enough to defeat the cancer completely.
Precision Targeting in Cancer Therapy
To enhance the elimination of cancer cells, Craik partnered with Dr. Mike Evans, a radiology professor at UCSF.
They aimed to modify their strategy by maintaining the KRAS-targeting drug that marked the malignant cells but adding radioactive elements to the antibodies.
This new approach yielded remarkable results, completely clearing lung cancer in the mouse models while minimizing harmful effects.
Evans pointed out the precision of this method, which effectively targets only cancer cells, leveraging the powerful effects of radiation while leaving surrounding healthy cells untouched.
Craik emphasized another advantage: this technique allows for precise control over the radiation dose, using only what is necessary to obliterate the cancer—a stark contrast to traditional external beam radiation strategies.
As the UCSF team looks to extend their groundbreaking treatment to a broader range of patients, they are working on developing antibodies capable of recognizing the various forms of KRAS prevalent in different individuals.
Their promising findings have laid a robust foundation for this goal.
In the quest for improvement, Dr. Kliment Verba, an assistant professor at UCSF, has employed cryo-electron microscopy to investigate the intricate structure of what they call the “radiation sandwich.” His insights are leading to the development of enhanced antibodies.
Verba noted that the unique visibility of the drug-KRAS peptide significantly boosts the antibody’s capability to bind to its target, marking a promising advance toward personalized radiation therapies that could transform cancer care.
Source: ScienceDaily