Targeted cancer therapies block specific molecules involved in cancer-causing pathways. Some, such as the recently approved skin cancer drug vismodegib (marketed as Erivedge), have had remarkable results - for a while. Vismodegib works by blocking the activity of a biological signaling cascade called the Hedgehog pathway. But eventually tumors become resistant.
Now, Stanford dermatologist Anthony Oro, MD, PhD, and his colleagues have published a study (subscription required) in Nature describing how targeting another, previously unknown component of the pathway can kill even vismodegib-resistant cancer cells. From our release:
"These new, highly targeted therapies work really well," said dermatology professor Anthony Oro, MD, PhD, who was one of several Stanford researchers involved in the multiyear effort that brought vismodegib to market in 2012. "But this type of treatment is a race against evolution. Within a year, many of the tumors recur when the cancers become resistant to the inhibitor." [...]
"Although these tumors evolve in response to targeted drug treatment, we believe there's a limited number of ways they can escape these therapies," said Oro. "If we were able to hit them at the time of diagnosis with drugs that target more than one step in the pathway, they may be less able to evade treatment. We've identified a new target in the Hedgehog pathway and we've developed an inhibitor of this target that we hope will work in human cancers."
The researchers, including postdoctoral scholar Scott Atwood, PhD, hope that the finding can one day help patients by providing another way to tackle skin cancers called basal cell carcinomas - either sequentially or in tandem at the time of diagnosis. As explained in our release:
Taken together, the recent studies illustrate the nature of the constant battle among physicians and the rapidly growing and changing cancer cells they strive to eradicate. Targeted treatments that focus on unique vulnerabilities exhibited by specific types of cancers can be highly effective. They can also minimize the unpleasant side effects of less-specific treatments that kill many other non-cancerous cells. But their very specificity encourages and drives the tumor cells to evolve resistance in a way that might not be possible against a more broad-based therapeutic approach. Many researchers believe that a multipronged attack targeted at more than one point in critical cancer-causing pathways could be an effective way to combat resistance.
Previously: Studies show new drug may treat and prevent basal cell carcinoma, Hope for basal cell carcinoma prevention? and Common drug might help prevent skin cancers