Chemotherapy kills tumor cells, but it also wreaks havoc on the rest of the body. A team of researchers led by Igor Roninson of the South Carolina College of Pharmacy just reported the discovery of a new class of drugs that reduces the adverse effects of cellular damage from chemotherapy.
The advance appears to be applicable to a wide range of cancers and has the potential to improve the efficacy of chemotherapy and increase the time of remission after chemotherapy. It may also be developed into a promising new therapy for age-related diseases, such as Alzheimer's.
"Conventional anticancer drugs, while essential for current cancer therapy, have side effects that can damage healthy cells and cause them to promote the growth of surviving cancer cells," said Roninson, the SmartState Endowed Chair of Translational Cancer Therapeutics at the South Carolina College of Pharmacy, who has appointments with both the University of South Carolina and the Medical University of South Carolina. "We needed to find a way to interrupt that process."
The cancer-supporting activity of conventional drugs appears to occur, in part, because these drugs damage both tumor cells and the patient's normal tissues, causing numerous changes in drug-damaged cells, including the onset of senescence. Cellular senescence, or aging, can result from changes in the chromosomes that develop with age, or it can be induced by DNA damage caused by traditional anticancer drugs and other factors. The senescent cells and other damaged cells have been shown to produce cancer-supporting molecules as well as proteins implicated in other diseases of old age, such as Alzheimer's disease and arthritis.
The importance of these secretory activities of senescent cells has been convincingly demonstrated in recent studies, but no practical method for blocking this pattern was previously known. Roninson's team has just reported in the Proceedings of the National Academy of Sciences the development of Senexin A, the first of a series of chemicals that inhibit the secretory pattern of the senescent and other damaged cells. This inhibition is key to reducing the cancer-promoting effects of chemotherapy.
In one of the experiments reported, carried out by co-author Hippokratis Kiaris at the University of Athens (Greece), mice were treated with a commonly used anticancer drug. After the mice recovered from this treatment, both drug-treated and untreated mice were injected with cancer cells.
Strikingly, mice pretreated with the anticancer drug developed tumors much more efficiently than the untreated mice. Furthermore, the blood of mice pretreated with the anticancer drug had a higher content of proteins that stimulate the growth of tumor cells.