Research Helps Discover What's Behind Ovarian Cancer Recurrence

Research shows that molecular techniques can help identify ovarian cancer recurrence, but researchers still need to investigate more of the molecular phases of ovarian cancer in order to gain a better understanding and method of predicting the recurrence of the disease, according to Dr. Peter Dottino.

There are currently various studies going on in this area that have revealed some interesting results.

The use of WEE1 inhibitors have shown evidence of chemo potentiation in tumors that are deficient of p53, as nearly 96 percent of ovarian cancer patients with serious, high-grade types possess the p53 tumor suppressor gene. In the phase II clinical trial of one recent study, researchers explored the WEE1 inhibitor AZD1775 along with the carboplatin in patients who possess the TP53 mutated, refractory/relapsed ovarian cancer in order to determine the overall response rate (ORR), along with the progression-free survival (PFS), and the overall survival (OS).

The manageable safety profile included the combination that was linked to an ORR of 43 percent and one patient who had a prolonged complete response. The median PFS was 5.3 months with one patient with an ongoing response for more than 31 months and the median OS was 12.6 months with another patient with ongoing response for more than 42 months.

Dr. Peter Dottino, the professor of obstetrics, gynecology, and reproductive science at the Mount Sinai Hospital, discussed the use of molecular methods as a way to identify ovarian cancer after chemotherapy treatment and how research on this subject affects the future of the field in an interview during the 2017 OncLive State of the Science Summit on Treatment Options in Ovarian Cancer.

Updated approaches to ovarian cancer recurrence

When asked what the highlights of the presentation on ovarian cancer was, Dottino responded, "The information in the presentation was on a few of the molecular techniques that have been developed at the Mount Sinai School of Medicine that are able to detect ovarian cancer after being treated with chemotherapy. The process that we used allowed us to go back into the biobank, which is about 10 years old and where we have saved specimens and DNA from both primary and recurrent tumors, as well as took a second look at washings that were removed from patients who had gone through laparoscopy.

What we actually did was simply ask ourselves what the genetic makeup is of both the primary and recurrent tumor are and whether or not we could predict and locate the same mutations that we found in the primary tumor in the washings removed at the second look as well. Using a 56-panel using next generation sequencing, we found that in 5 of the patients who we did the second look on, mutations were discovered. We also found that in 3 out of the 5 patients that we classified as negative second looks we also found the deleterious p53 mutations and discovered that those patients continued on to recur.

Because we found those mutations in the primary, the wash, and in the second look, we were able to confirm that there is indeed a heterogeneity to ovarian cancer. There are, however, certain genes that can be found in the primary tumor that are not found in the wash or in the recurrence. We presume that the selective pressure that is applied by the use of chemotherapy may actually kill those clones and this supports the theory of heterogeneity of the tumors. This occurrence seems very common in high-grade, serous tumors and is most likely a reason why the majority of patients who have high-grade serous tumors in the ovary will ultimately have a relapse."

Read on to learn more about the implications of this research.