Targeted cancer therapies are designed to be more precise than traditional chemotherapy drugs. With their ability to home in on cancer cells, these cruise-missile-like drugs are less toxic than the carpet-bombing chemotherapy drugs that kill all rapidly dividing cells—both healthy and cancerous. But mouse studies of the new class of targeted drugs called IAP antagonists have suggested that less toxic does not mean toxic-free.
Inhibitor of apoptosis (IAP) antagonists—now in early clinical trials for breast, liver, lung, pancreatic, prostate, ovarian, skin and blood cancers—block the signals that allow cancer cells to cheat death. But they also activate pathways that control cells that break down bone. In a study published in February in Cancer Discovery, pathologist Deborah V. Novack and her colleagues at Washington University School of Medicine in St. Louis found that mice given IAP antagonists had an increased risk of cancer spreading to their bones.
“There are very few molecular pathways that are 100 percent exclusive to tumor cells,” says Novack. “You can’t completely avoid the potential normal roles of the proteins being targeted by the drugs.”
Last year, researchers reported that Zelboraf (vemurafenib), which had recently been approved to treat a type of metastatic melanoma, could speed up the growth of squamous cell carcinoma, another type of skin cancer. And in May 2012 the U.S. Food and Drug Administration reported that data collected over the previous seven years showed that the multiple myeloma drug Revlimid (lenalidomide) increased the risk of a new type of cancer.
Side Effects Watch
Before starting a targeted drug, ask your doctor:
- How much is known about the drug’s side effects?
- What are the most common side effects?
- What are the rare but serious side effects?
- What should I do if I notice unusual side effects or symptoms?
The first hint of such side effects often crops up during laboratory studies, says Gerald S. Falchook, a clinical researcher at the M. D. Anderson Cancer Center in Houston. “When we start a human trial,” says Falchook, “we build within it parameters to monitor for side effects that we might expect based on what we know about the drug target and what we learned from the animal research.” This allows many side effects to be discovered before a drug is approved.
Novack’s mouse studies found that bone-building drugs called bisphosphonates can counteract the bone-related effects of an IAP antagonist. But, to date, researchers have not changed their trial regimens. “There’s really no reason at this point based on the clinical experience to [prevent] something we’re not seeing,” says Ali Fattaey, the president and chief operating officer of the drug company Curis, which is developing the IAP inhibitor CUDC-427.
Novack encourages patients to report any unusual symptoms or side effects to their doctors. “Patients shouldn’t ignore things that might be unexpected,” she says, “especially if they’re on a newer therapy.”
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