UC San Francisco researchers have developed a new variety of targeting system for chemotherapy drugs based on the unusually high free iron content of many cancer cells — distinct from the protein-bound iron that is common throughout the body’s cells. In experiments in mice and cancer cell lines, the researchers succeeded in selectively killing off cancer cells while avoiding chemo’s typical toxic effects on healthy cells, enabling them to boost the tolerable dose by as much as 50-fold.
The new approach — which involves enclosing a potent chemotherapy drug within a protective chemical framework that only releases the drug when it encounters the high-iron environment of a tumor — could add a valuable new tool to oncologists’ increasingly precise pharmaceutical arsenal, enabling them to target cancers with much higher doses of chemotherapy drugs while significantly reducing the grueling side effects for patients.
“Given chemotherapy’s primary role in cancer treatment, we must continue to find ways to enhance its efficacy while mitigating the side effects, which can often be debilitating for patients,” said Alan Ashworth, PhD, FRS, president of the UCSF Helen Diller Family Comprehensive Cancer Center. “These findings are exciting and promising because they offer clues into exploiting a tumor’s vulnerabilities while thwarting drug resistance and recurrence down the line.”
The new study, published in its final version online December 12, 2016 in the Journal of Medicinal Chemistry, was conducted in the lab of Adam Renslo, PhD, a UCSF associate professor of pharmaceutical chemistry and member of the Helen Diller Family Comprehensive Cancer Center, and led by then-graduate student Benjamin Spangler, PhD.
“Traditional chemotherapy drugs are very effective at killing cells, but generally they are not very selective, which is why patients experience such terrible side effects,” Renslo said. “In contrast, new oncogene-targeted drugs are much more selective, but they’re typically only effective against very particular forms of cancer — plus, the tumors are frequently able to evolve resistance and recur. This new approach combines some of the benefits of each: it has the inescapable destructive power of chemotherapy, but targets that power selectively to cancer cells.”
Read more at UCSF.edu