Anticancer Agent and Radiotherapy Destroy Tumors but Protect Healthy Cells

Although radiation treatments have recently become much more optimized, it is still difficult to both sufficiently dose the tumor while sparing the surrounding tissue. A new anticancer drug currently under clinical development may help tackle this problem by protecting normal cells, but not the cancerous ones, from the effects of radiation. The research additionally suggests this drug may also be useful in treating accidental exposure to radiation.

“It was a stroke of luck that the drug that most effectively protected normal cells and tissues against radiation also has anticancer properties, thus potentially increasing the therapeutic index of radiation therapy,” said Ulrich Rodeck, MD, PhD, a professor of dermatology and cutaneous biology and radiation oncology at Thomas Jefferson University (Philadelphia, PA, USA) and senior author on the study, which was published November 14, 2014, in the journal Molecular Cancer Therapeutics.

Together with first author Vitali Alexeev, PhD, assistant professor, dermatology and cutaneous biology, Dr. Rodeck and colleagues evaluated five compounds that were shown to have radiation-protective properties in earlier studies. The researchers gave the mice one of the five compounds a day before and for several days after radiation treatment. A compound called RTA 408 emerged from this screen as a strong radiation protector and its effect was comparable to the only drug currently approved by the US Food and Drug Administration (FDA) for that purpose. (The approved drug, called amifostine, however, has a number of side effects including severe nausea or vomiting that make it an unappealing choice for clinicians.) Sites that are typically most vulnerable to radiation damage including the gut and blood cells in the bone marrow were both protected in mice treated with RTA 408.

Using human prostate cancer cells growing in lab mice, the researchers also showed that RTA 408 did not provide radiation protection to the cancer cells. In fact, when RTA 408 was administered by itself, without radiation, it also slowed the growth of human prostate cancer transplants in mice. In combination, it further augmented the tumor growth inhibitory effects of radiation. “It was really exciting to see,” stated Dr. Rodeck, “that combining radiation and RTA-408 more effectively inhibited tumor growth compared to using either one or the other as single treatment modalities.”

Dr. Rodeck and colleagues plan to continue to research the molecular foundations of these radiation-protective effects to better understand how precisely this compound works and how its process of action might be optimized for clinical applications. RTS 408 is currently being developed by REATA Pharmaceuticals (Irving, TX, USA) for a variety of clinical applications, including a trial currently enrolling patients for a topical form of the drug applied to patients who experience radiation dermatitis.

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