Aug 30, 2012 - Mesothelioma Treatment May Increase Resistance to Chemotherapy
Mesothelioma treatments are supposed to kill malignant tumors and improve a patient’s life but new research that is the culmination of years of work has discovered that certain chemotherapies may actually increase this type of asbestos cancer's resistance to treatment.
A group of researchers from the Fred Hutchinson Cancer Research Center in Seattle have discovered a key protein that actually makes certain types of cancer more resistant to chemotherapy. Unfortunately, this protein is sometimes created by genes damaged by chemotherapy. In essence, the most widely accepted treatment for various cancers, including malignant mesothelioma, may actually be contributing to the disease’s hardiness.
The study, reported in Nature Medicine, was headed by Peter Nelson, M.D. of the Hutchinson Center and Human Biology Division. While mesothelioma wasn’t part of the initial study, preliminary findings show similar resistance-building effects with a wide variety of cancers including breast, ovarian and prostate. The researchers also believe that this type of backsliding is most prevalent in patients suffering from cancers that have metastasized (moved to portions of the body not originally affected.) This is bad news for mesothelioma patients because cancer caused by asbestos is very aggressive and metastasizes often before it’s even discovered.
Nelson introduced this line of research as part of an ongoing effort in anti-cancer therapies that are examining these diseases on a molecular level. “Cancer therapies are increasingly evolving to be very specific, targeting key molecular engines that drive the cancer rather than more generic vulnerabilities, such as damaging DNA.” Indeed cancer, and especially mesothelioma, is a very specific disease with multiple factors drastically affecting disease progression and the effectiveness of treatment. As these treatments get more and more precise, scientists have discovered that “… the tumor microenvironment also can influence the success or failure of these more precise therapies.”
Specifically, Nelson’s team identified a protein labeled WNT16B. This protein is manufactured by genes associated with non-cancerous fibroblasts that have been altered during their exposure to popular chemotherapy drugs. Indeed, Nelson discovered that this protein can be found in levels up to 30 times higher in patients who have undergone chemotherapy than in those who have not.
This protein interferes with future treatments and effectively limits the potency of drug therapy. Due to the toxicity of chemotherapy, threatments cannot be delivered in levels high enough to effectively kill cancer in one or two doses but must be delivered sequentially over time in multiple doses. It is believed that while each dose kills some cancer cells, increasing damage to surrounding fibroblasts triggers the production of more and more of this protein. The protein makes specific cancer cells and those surrounding them more resistant to future rounds of chemotherapy, which means more cells will survive each successive dosage.
This study was a collaborative effort between Nelson and researchers at the University of Washington, Oregon Health and Science University, the Buck Institute For Research on Aging, and the Lawrence Berkeley National Laboratory. It was based on data culled from multiple sources including federally funded tissue banks and clinical trials.
Now that the exact mechanism of this protein resistance is understood, Nelson feels that future chemotherapy drugs or concurrent treatments could be developed which capitalized on this knowledge. It may be possible to circumvent or event prevent this protein’s synthesis and make cancer cells and their surrounding tissues more receptive to future chemotherapy drugs – which is good news for all cancer patients, including mesothelioma victims.
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