Ovarian cancer is considered the second most common gynecological malignancy, particularly in the western world. Generally, the ovarian cancer develops at the age of 40 but most develop after the age of 60. It is a difficult disease to treat and because of the absence of early warning signs, most of the cases are diagnosed at an advanced stage of the disease presenting poor prognosis. However, with the progression in the surgical procedure and with the advent of new drugs entering the clinic, it has become a chronic disease instead. But, if detected in the initial stage, about 90% of affected individuals could be cured.
The ovaries are made up of three forms of cells and hence the different types of tumor; epithelial tumors, germ cell tumors and stromal tumors. Although most of the epithelial tumors are benign, an estimated 85% of all ovarian cancers are of epithelial ovarian carcinomas. Also, the advances illustrated the significant role for the BRCA gene and the genetic screening for these mutations has resulted in improved preventative measures and accordingly the therapeutic development. The pap tests are not useful for the prediction of ovarian cancer but are only for the detection of cervical cancer and in a rare case, an advanced stage of ovarian cancer could be found. Therefore, an early identification of this disease could result in a better prognosis.
Most of the genetic mutations associated with ovarian cancer are sporadic meaning they are acquired and not inherited. In around half of the somatic mutations responsible for ovarian cancer, a mutation in the TP53 gene is responsible. The protein produced by this gene are called tumor suppressor and the mutation either reduces or eliminates the function to suppress tumor growth. The inherited cause of ovarian cancer is the result of the mutation in BRCA1 and BRCA2 which impairs DNA repair allowing the mutations to continue thus triggering tumor growth. The relationship of a woman developing ovarian cancer in her lifetime is around 1.6% compared to 40 to 60% risk among those with BRCA1 gene mutation and 20 to 35% for those with BRCA2 gene mutation.
New Types of Oral Contraceptives Associated with Reduced Risk of Ovarian Cancer
According to a study published in the BMJ, the new types of oral contraceptives with lower doses of oestrogens and newer progestogens are associated with reduced risk of ovarian cancer. This now serves as a reassurance among women where around 100 million of them are using hormonal contraceptives. The study analyzed the data of around 1.9 million Danish women in the age group of 15-49 between the years 1995 – 2014. The research shows that the cases of ovarian cancer were the highest among those who had never used oral hormonal contraceptives and that the use of hormonal contraception prevented an estimated 21% of ovarian cancers among this study population.
Advances in the Treatment of Ovarian Cancer
Although the current treatment options for epithelial ovarian cancer includes surgery and chemotherapy, it can result in complete remission and the recurrence rate also appears to be high. Currently, there are several new drugs under development and are being tested in clinical trials to determine their efficacy.
- Checkpoint inhibitor immunotherapy drugs could be an option for some of the women with ovarian cancer. A phase 2 study analyzed the efficacy of Keytruda (pembrolizumab) for women with advanced recurrent ovarian cancer. Patients with a higher combine positive score (CPS), i.e., more PD-L1 protein in their tumors, had a better rate of response.
- FDA granted regular approval for olaparib (Lynparza) for maintenance therapy of women with germline BRCA-mutated advanced ovarian cancer. Poly (ADP-ribose) polymerase (PARP) is a protein that the cancer cells depend on to keep DNA healthy and olaparib inhibits PARP from repairing DNA damage and it results in the death of cancer cells.
- Mirvetuximab soravtansine is currently in a phase III study and being compared with chemotherapy in platinum-resistant ovarian cancer and has emerged as a promising investigational agent. The initial findings have shown it can be safely combined with combinatorial partners and therefore plays an important role for patients with platinum-resistant ovarian cancer.
Screening Guidelines for Ovarian Cancer
As ovarian cancer does not normally present any symptoms in the initial stage of the disease, the research still continues to determine the best screening test. Currently, the two tests used are a transvaginal ultrasound and CA-125 blood test to determine ovarian cancer. The transvaginal ultrasound can detect a tumor in the ovary but cannot differentiate between cancer or benign tumor and in most of the cases, the masses are noncancerous. A blood test measures the quantity of CA-125 protein in the blood and most of the women with ovarian cancer present high levels of this protein. However, as women with other conditions such as pelvic inflammatory disease and endometriosis also show high-level of CA-125, a transvaginal ultrasound test may be recommended to determine the cause. According to the US Preventive Service Task Force (USPSTF), screening for ovarian cancer can present many false-positive results leading to an unnecessary surgical intervention for those without cancer. Also, the diagnostic guidelines recommend the surgical removal of the ovary to determine whether ovarian cancer is present rather than the tissue biopsy. Hence, USPSTF recommends against screening for asymptomatic women.
The Promise of a Vaccine for Ovarian Cancer
According to a new small trial, a personalized cancer vaccine is considered to be capable of inducing antitumor T-cell immunity among women with recurrent ovarian cancer. This vaccine is developed using autologous dendritic cells pulsed with autologous tumor lysate. The pilot study involved 25 patients with recurrent advanced epithelial ovarian cancer and the result of the study was published in Science Translational Medicine. A total of 392 vaccine doses were administered which were well tolerated by the patients. Although individuals show longer progression-free survival when their T-cells responded to autologous tumor antigen, further clinical testing is required.