New Anti-Cancer Drug for Aggressive Brain Tumors




Drugs_Clinical_Trials2.jpgResearchers are constantly trying to find new drugs or forms of therapy that can be used to treat cancer. Quite often when a possible treatment is discovered, being allowed to test a drug or other experimental cancer treatment at a clinical level is difficult. For example, after an anti-carcinogenic drug has been thoroughly tested at the experimental level it is necessary to test it in humans to analyze factors such as the drug’s anti-tumor activity, its ability to interact with a specific target, and to discover which patients are more likely to benefit from the drug. These types of early clinical trials are the key in the successful implementation of effective anti-tumor drugs and therapies.

One such study was done to treat a small group of glioblastoma patients with an experimental drug called rapamycin since they needed to undergo surgery because their glioblastoma tumors returned. Glioblastomas are aggressive brain tumors that are very invasive and exhibit rapid metastasis. Currently chemotherapy and surgery are not effective treatments for this type of cancer and in most cases, the tumors often return after treatment. This has caused researchers to look for alternative forms of treatment for glioblastomas that include anti-tumor drugs. An interesting discovery about glioblastoma cases is that approximately 40% of patients who develop glioblastomas have a gene called PTEN that becomes inactive. PTEN is a tumor suppressor gene that sensitizes cancer cells to drugs called mTOR inhibitors when it is inactivated. mTOR is a protein that plays a role in cell growth and proliferation. Rapamycin, also called Sirolimus, is an mTOR inhibitor and the anti-carcinogenic and well as immunosuppressive affects of these types of drugs are currently being evaluated.

For this study, 15 patients whose glioblastoma tumors returned were treated with different amounts of rapamycin one week before and after surgery. Each of these patients had tumors that did not express the PTEN gene and if the tumor appeared to be progressing after surgery the rapamycin treatment was discontinued. The purpose of this study was to determine if the drug could inhibit tumor growth and if so, at what concentration. In addition the researchers were hoping to reveal which patients were more likely to respond to rapamycin treatment.

The results of this study showed that the rate of tumor cell proliferation decreased in 7 of the 15 patients treated with rapamycin after surgery, and severe toxicity did not occur in most of the patients. The reduction of tumor cell proliferation was directly correlated to the inhibition of the mTOR protein. Scans that were obtained from 2 patients even showed signs that the tumor mass was decreasing. Unfortunately, when tumor cells that reacted to rapamycin in patients were tested in a laboratory setting, the cells no longer responded to rapamycin treatment. This appeared to be due to the drug’s inability to penetrate the tumor ex vivo. In addition, the treatment of rapamycin led to the activation of a protein called Akt in some patients, which decreased the time period between surgery and a reoccurrence of their tumor.

These results showed that although rapamycin caused a reduction of tumor cell proliferation in some glioblastoma patients, in others it activated a second protein that accelerated the progression of the disease. This strengthens the point that these types of studies are essential. The side effects of this drug in some patients is life threatening so it is important to analyze the clinical effects from a small group of selected patients before the drug is distributed on a large scale level or in clinics nationwide.

Reference

Cloughesy, T.F., Yoshimoto, K., Nghiemphu, P., Brown, K., Dang, J., Zhu, S., Hsueh, T., Chen, Y., Wang, W., Youngkin, D., Liau, L., Martin, N., Becker, D., Bergsneider, M., Lai, A., Green, R., Oglesby, T., Koleto, M., Trent, J., Horvath, S., Mischel, P.S., Mellinghoff, I.K., Sawyers, C.L. (2008). Antitumor Activity of Rapamycin in a Phase I Trial for Patients with Recurrent PTEN-Deficient Glioblastoma. PLoS Medicine, 5(1), e8. DOI: 10.1371/journal.pmed.0050008

Karen Vieira, MBA, PhD

Karen Vieira, MBA, PhD, has written about medical research, medical procedures, food ingredients, herbal remedies, pharmaceutical drugs, condo construction, real estate and computer consulting to mention a few.
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