For most people, the only thing worse than hearing the diagnosis “cancer” is hearing that it has returned.

Dr. Ilana Chefetz, leader of The Hormel Institute’s “Cancer Stem Cells and Necroptosis” lab, published new discoveries about ovarian cancer chemo resistance and recurrence in the top journal Cell Reports.  Her research project included collaborations with Drs. David Lombard, Charles Landen, Thomas D. Hurley, Scott D. Larsen and Ronald J. Buckanovich.

While most ovarian cancer patients will initially respond to treatment, an alarming number of women still experience relapse. The article, “A Pan-ALDH1A Inhibitor Induces Necroptosis in Ovarian Cancer Stem-like Cells” looks at novel inhibitors that target specifically the highly chemo resistant cancer stem cell (CSC). 

“It is critical progress to identify when and how the resistance to chemo occurs, so that we may target these roadblocks,” said Dr. Ilana Chefetz.“We identified ALDH1A inhibitors that furthers our ultimate goal which is to eliminate resistant ovarian cancer cells so we can prevent recurrent ovarian cancer.”

Ovarian CSCs are defined by the activity of an enzyme called ALDH (Aldehyde Dehydrogenase).  The high relapse rate is highly consistent with a cancer stem cell (CSC) model. The CSC hypothesis suggests that, rare, chemo resistant CSC is capable of proliferating, causing relapse of the disease as well as resistance to chemotherapy.

The hypothesis of the research was that ALDH inhibitors would act as CSC targeted therapeutics. The majority of ovarian cancers harbor p53 mutations, making them resistant to apoptosis (cell death) by radiation therapy or chemotherapy.   As ALDH inhibitor induces programmed cell necrosis (necroptosis) – an alternative programmed cell death, it is possible to bypass resistance. Dr. Chefetz believes it is possible an agent, equipped to eliminate ovarian CSC, alone or in combination with conventional chemotherapeutic drugs may overcome chemo resistance in ovarian cancer.