Mesothelioma Therapy Aims to Destroy Root of Cancer

May 30, 2009

Mesothelioma is an uncommon neoplasm derived from the cells lining the pleura and peritoneum. Currently there are approximately 3,000 new cases diagnosed in the United States each year. The relationship between asbestos exposure and mesothelioma is well established. The interval between asbestos exposure and tumor formation is commonly 3 to 5 decades.

Mesothelioma generally has a short survival time following diagnosis and treatment is considered mainly to be palliative, rarely resulting in a cure. Research is ongoing in looking for new therapeutic treatments that may help to increase survival time and quality of life for mesothelioma sufferers.

Recently, novel therapies aimed at attacking cancer at the root of its cause, the cancer stem cell, were discussed at the American Association for Cancer Research in April. The research is based upon the theory that cancers grow from stem cells, so if a treatment can be found that attacks the stem cells themselves versus the tumor cells, the cancer can be destroyed and kept from recurring. The root cause of cancer and stem cells is multicellularity. Even when chemotherapy or radiation kills tumor cells, stem cells are left behind and can rapidly reproduce, causing tumor relapse.

Cancer stem cells are thought to be ultimately responsible for the growth of tumors and are often resistant to current therapies. Therefore, chemotherapy and radiation may affect cancer cells and tumors, but leave stem cells unaffected. The stem cells then proliferate, generating and perpetuating cancer tumors over time.

Cancer stem cells are found within tumors and are thought to generate tumors through the stem cell process of self-renewal and differentiation into multiple cell types, including malignant ones. Developing specific therapies that target stem cells could prevent relapse and metastasis. Such treatments could also prevent recurrence of chemotherapy resistant cells, a common result of traditional therapies where the cancer is first reduced but then reappears with increased chemoresistancy.

Research began to study the possibility of combining radiation and/or chemotherapy with a drug that interfered with DNA repair. In non-human studies, the combination treatment killed not only the tumor cells but also the stem cells. Cancer Research UK uses a unique whole-lung imaging method to examine and identify the location of stem cells in the lungs of mice to help study the role they play in both healthy and damaged tissue. Clinical trials are testing drugs that hit molecular targets highlighted by cancer stem cell studies. Researchers are looking for drugs that hit only the unhealthy stem cells and not the healthy ones in order to prevent recurrence of tumors and reduce chemotherapy and radiation resistance.

If results from Phase I and II clinical trials continue to hold true, cancer stem cells could be the most promising therapeutic target and eventually lead to a curative treatment for lung cancer such as mesothelioma. The goal is to knock out the cancer stem cells themselves, preventing the tumors ability to grow back.

Understanding the mechanisms by which stem cells resist common therapies may improve patient outcomes by developing new approaches that directly target the root of cancer and overcome common resistant mechanisms. Current research into the cellular and molecular biology of normal and cancer stem cells holds much hope for the improvement of survival and quality of life for patients with cancer, including those suffering from mesothelioma and other asbestos related lung cancers.

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