New Approaches and Biomarker Candidates for the Early Detection of Ovarian Cancer

OVARIAN CANCEROvarian cancer (OC) is a disease that most often affects post-menopausal women who present abdominal discomfort and bloating over a few months prior to detection.The majority of patients are diagnosed at advanced stages of the disease as the early stages are commonly asymptomatic (Jayson et al., 2014).According to Global Cancer Statistics 2020, OC is the seventh most common cancer in women worldwide accounting for around 314,000 new cases (3.4% of all new cancer cases in females) annually (Sung et al., 2021).In 2021 it established itself as the ninth most commonly diagnosed cancer amongst Australian women with 1720 new cases and 1,042 reported deaths (www. canceraustralia.gov.au).Prognosis is significantly determined by the stage of diagnosis where survival for stages I, II, III and IV is 73-92%, 45-55%, 21% and <6%, respectively 1 , underscoring the need for better early detection of ovarian cancer.There are four main types of OC: epithelial, Germ cell, sex chord and stromal, with each having different epidemiological statistics, and with epithelial ovarian cancer (EOC) accounting for approximately 90% of all cases (Smith et al., 2006).In EOC there are histological subtypes, though most patients have high-grade serous ovarian cancer, a disease characterised by p53 gene abnormalities (Köbel, 2010).Some high grade serous ovarian cancers are caused by deleterious mutations of BRCA1 and BRCA2 genes, while others arise from a combination of somatic mutations (Network, 2011).The most common and effective management of the disease is a combination of surgery with chemotherapy.Surgical removal of cancer mass almost always occurs after diagnosis however, this is not always feasible when the cancer is very advanced.Furthermore, although surgery has proven effective in early stages of the disease, most patients diagnosed at advanced stages will go on to develop many iterations of recurrent disease (Jayson et al., 2014).Cancer Antigen-125 (CA-125) and trans-vaginal imaging are currently routinely used as part of ovarian cancer diagnosis.Blood level of CA-125 is the most widely used serum biomarker, but it lacks the sensitivity or specificity to be used alone as a screening test (Jayson et al., 2014).It is also not useful for early diagnosis as CA-125 expression levels are too low for accurate detection and there are also several other conditions including endometriosis (Nisenblat et al., 2016), gall bladder (Wang, 2014) and liver cancer (Devarbhavi et al., 2002) where CA-125 levels are elevated, leading to false positive results.Likewise, it is often difficult to detect small early-stage tumors with trans-vaginal imaging.Hence, diagnosis often involves invasive techniques like laporascopy and tissue biopsies.It is therefore clear that early diagnosis of ovarian cancer requires improved screening tests that can be performed easily and inexpensively, as well as achieving high sensitivity and specificity.