Through the Looking Glass: Updated Insights on Ovarian Cancer Diagnostics.

Epithelial ovarian cancer (EOC) is the deadliest gynaecological malignancy and the eighth most prevalent cancer in women, with an abysmal mortality rate of two million worldwide. The existence of multiple overlapping symptoms with other gastrointestinal, genitourinary, and gynaecological maladies often leads to late-stage diagnosis and extensive extra-ovarian metastasis. Due to the absence of any clear early-stage symptoms, current tools only aid in the diagnosis of advanced-stage patients, wherein the 5-year survival plummets further to less than 30%. Therefore, there is a dire need for the identification of novel approaches that not only allow early diagnosis of the disease but also have a greater prognostic value. Toward this, biomarkers provide a gamut of powerful and dynamic tools to allow the identification of a spectrum of different malignancies. Both serum cancer antigen 125 (CA-125) and human epididymis 4 (HE4) are currently being used in clinics not only for EOC but also peritoneal and GI tract cancers. Screening of multiple biomarkers is gradually emerging as a beneficial strategy for early-stage diagnosis, proving instrumental in administration of first-line chemotherapy. These novel biomarkers seem to exhibit an enhanced potential as a diagnostic tool. This review summarizes existing knowledge of the ever-growing field of biomarker identification along with potential future ones, especially for ovarian cancer.

Developing Clinically Relevant Acquired Chemoresistance Models in Epithelial Ovarian Cancer Cell Lines.

Chemoresistance, the ability of cancer cells to overcome therapeutic interventions, is an area of active research. Studies on intrinsic and acquired chemoresistance have partly succeeded in elucidating some of the molecular mechanisms in this elusive phenomenon. Hence, drug-resistant cellular models are routinely developed and used to mimic the clinical scenario in-vitro. In an attempt to identify the underlying molecular mechanisms that allow ovarian cancer cells to gradually acquire chemoresistance, we have developed isogenic cellular models of cisplatin and paclitaxel resistance (singularly and in combination) over six months, using a clinically relevant modified pulse method. These models serve as important tools to investigate the underlying molecular players, modulation in genetics, epigenetics, and relevant signaling pathways, as well as to understand the role of drug detoxification and drug influx-efflux pathways in development of resistance. These models can also be used as screening tools for new therapeutic molecules. Additionally, repurposing therapeutic agents approved for diseases other than cancer have gained significant attention in improving cancer therapy. To investigate the effect of metformin on acquirement of chemoresistance, we have also developed a combinatorial model of metformin and platinum-taxol, using two different strategies. All these models were subsequently used to study modulation in receptor tyrosine kinase pathways, cancer stem cell functionalities, autophagy, metastasis, metabolic signatures, and various biological processes during development of chemoresistance. Herein, we outline the protocols used for developing these intricate resistant cellular models.