An Important Drug Target Discovered for Advanced Ovarian Cancer

Advanced serous ovarian cancer is the most common type of ovarian cancer . Most patients are diagnosed at an advanced stage because ovarian cancer does not cause symptoms early on; at this stage, the cancer becomes resistant to chemotherapy over time and recurs (returns despite treatment). In July 2019, a study published in Molecular Cancer Research identified an enzyme responsible for the growth of advanced serous ovarian cancer cells: IDH1 (isocitrate dehydrogenase 1). Blocking the enzyme puts cancer cells into a dormant state.

One in every 78 women develops ovarian cancer. When ovarian cancer is detected early, the 5-year survival rate is over 90%. However, ovarian cancer symptoms are quite vague, and there is no cancer screening test for early detection. Only 20% of patients can be diagnosed at an early stage. By the time most patients are diagnosed with ovarian cancer, the cancer has already undergone metastasis . In 70% of patients with advanced serous ovarian cancer, the disease recurs and resistance to chemotherapy develops. New-generation treatment approaches are therefore needed.

Recently, a growing number of studies have suggested that ovarian cancer originates in the fallopian tube . This study compared how healthy and cancerous fallopian tube cells use sugar. Byproducts produced during cellular metabolism were analyzed using mass spectrometry .

According to the Spectrometry Results:

• Healthy cells were found to convert sugar to lactate using aerobic respiration. Cancer cells, by contrast, were found to use sugar in the citric acid cycle. Cancer cells use glycolysis to produce large amounts of energy, which is why many cancer treatments target glycolysis. However, targeting glycolysis also harms healthy cells. The researchers therefore focused on the citric acid cycle.
• When the IDH1 enzyme was blocked, the growth of both cells in the tissue where the tumor originated and cancer cells that had migrated to other organs was observed to stop. IDH1 is an important enzyme involved in the citric acid cycle.
• The results of this study, together with data from other studies, showed that low levels of this enzyme were associated with longer progression-free survival,
• The IDH1 gene was found to be in its normal (nonmutant) form in advanced serous ovarian cancer.

What Does This Study Mean for Us?

• An important drug target has been discovered for advanced serous ovarian cancer, a disease with limited treatment options. The IDH1 enzymesupports the growth of ovarian cancer cells.
• Blocking the IDH1 enzyme causes cancer cells to enter a “dormant” state.
• There is an FDA-approved drug that targets the IDH1 enzyme. Further studies are planned to determine whether a new agent that blocks IDH! can be used to treat ovarian cancer.