An article published in June in the journal Molecular Cell reports research scientists have developed a drug that prevents a key growth process in cancer cells from starting, cutting off nutrients the deadly cells need in order to live.
The cancer cell growth process targeted in the research is called autophagy – from the Greek “auto” (self) and “phagein” (to eat). It’s normally used by a cell to recycle its own damaged elements for further good purposes; unfortunately, the process can be co-opted by cancer cells to reap the energy needed to support their rapid destructive reproduction.
Dr. Raul Storey, a medical oncologist affiliated with Sebastian River Medical Center, says, “Cancer is an increased production of disorganized cells in one type of tissue. As the cells replicate, they need food. If they don’t have enough food available to them, they turn to autophagy.” He says that, while the research is preliminary, it also is very interesting.
This autophagy-inhibiting drug, which has the catchy name of SBI-0206965, could make it possible to squash cancer before it musters one last stand. The drug targets ULK1, an enzyme that initiates autophagy; importantly, it appears to do so without affecting healthy cells.
Reuben Shaw is a professor in the Molecular and Cell Biology Laboratory at the Salk Institute; he is one of the authors of the study. Shaw says, “The finding opens the door to a new way to attack cancer.” He adds that the drug will probably find the greatest utility in combination with targeted therapies – drugs or other substances that block the growth and spread of cancer by interfering with specific molecules.
Sebastian’s Dr. Storey spoke enthusiastically about targeted therapies, which he sees as the next big breakthrough in treating cancer. “It’s a very personalized approach,” he says. “The individual’s genetic profile will help determine how to target mutations.”
One big take-away from the study is that SBI-020695 could make existing anti-cancer treatments much more effective. Dr. Storey says this is important, as many cancers are currently treated by a combination of chemotherapy drugs – the “cocktail” approach. “Different drugs have different mechanisms of action,” he says. “Because of that, they are often combined, to a good effect. But adding together different drugs increases the risk of side effects.” He adds that the possibility of combining chemotherapy with a drug that can stop autophagy is very exciting.
The Sanford Burnham Prebys Medical Discovery Institute, with locations in Orlando and La Jolla, California, also participated in the study. Nicholas D.P. Cosford, a professor at SBP, says that SBI-020695 targets ULK1 (the bad guy in this instance) in tumor cells, not just in a test tube. Cosford says, “Our work provides the basis for a novel drug that will treat resistant cancer by cutting off a main tumor cell survival process.”
SBI-0206965 successfully killed a number of cancer cell types – including human brain cancer cells and both human and mouse lung cancer cells. Shaw says, “An important next step will be testing this drug in other types of cancer and with other therapeutic combinations.”
The paper published Molecular Cell states that many tumors become addicted to autophagy for survival; therefore inhibiting autophagy is a potentially broadly-applicable cancer therapy.
It is also seen as real plus that SBI-0206965 targets the enzyme that kicks off the autophagy process, as there may be fewer side effects and other unintended consequences than with drugs which disrupt autophagy in its later stages.
Additionally, the researchers say – and Dr. Storey agrees – that the results of this study may hold promise beyond cancer therapies, as defects in autophagy have been linked with infectious diseases, heart problems, and neurodegeneration diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, and ALS.
“This research could have a positive impact on a number of chronic diseases,” Dr. Storey says.
Dr. Storey’s private practice is part of Florida Cancer Specialists, with locations at 1880 37th St. in Vero Beach (772-589-0879) and 13060 US Hwy 1, Suite A, in Sebastian (772-228-3381).
