The researchers, led by David Llobet-Navas from the Institute of Genetic Medicine at Newcastle University and with support from collaborators at Institute of Biomedical Research Lleida and the Bellvitge Biomedical Research Institute (IDIBELL) in Barcelona, report on their findings in Autophagy.
Endometrial cancer is the most common gynaecological malignancy in women that appears in the inner lining of the uterus. Abnormal bleedings represent the main cause of diagnosis of EC, which is often found at early stages and confined within the womb. In these cases primary surgery is often curative. Unfortunately, 15-20% of early-stage cases recur after surgery and patients need to be treated with radiation therapy, chemotherapy, or both. Patients diagnosed with more advanced forms of the disease are also provided with these standards of care.
Treatment failure, defined as recurrence or overt dissemination (metastasis), is unfortunately common and made worse by the unavailability of established second line treatments. As a consequence, the prognosis of patients with recurred or metastatic endometrial cancer is poor with median survival rates of less than one year.
Autophagy protects endometrial cancer cells against targeted agent
Over the last years, our knowledge about autophagy (a cellular process in which cells degrade their own structures in order to obtain energy and to face nutrient starvation) has increased considerably and their discoverers have recently been awarded with the 2016 Nobel Prize.
The study by Dr Llobet-Navas and colleagues describes how endometrial cancer cells resist treatment using the anticancer compound sorafenib, a broad-spectrum kinase inhibitor and antiangiogenic agent, by inducing autophagy. By linking molecular biology, systems biology and avatar models the study describes how sorafenib activates the stress signalling molecules MAPK/JNK that will, in turn, trigger protective autophagy.
The results of this study provide insights on why sorafenib exhibited modest effects in clinical trials for endometrial cancer patients and has important clinical implications since no targeted therapies have been implemented in this malignancy so far. The authors postulate that autophagy inhibition could potentially be used as a therapeutic approach in combination with sorafenib in recurred or metastatic endometrial cancer patients.
Reference: Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer. Nuria Eritja, Bo-Juen Chen, Ruth Rodriguez-Barrueco, Maria Santacana, Sonia Gatius, August Vidal, Maria Dolores Marti, Jordi Ponce, Laura Bergada, Andree Yeramian, Mario Encinas, Joan Ribera, Jaume Reventos, Jeff Boyd, Alberto Villanueva, Xavier Matias-Guiu, Xavier Dolcet, David Llobet-Navas. Autophagy. doi: 10.1080/15548627.2016.1271512