An Overview of Candidate Therapeutic Target Genes in Ovarian Cancer

Abstract

Ovarian cancer (OC) shows the highest mortality rate among gynecological malignancies and, because of the absence of specific symptoms, it is frequently diagnosed at an advanced stage, mainly due to the lack of specific and early biomarkers, such as those based on cancer molecular signature identification. Indeed, although significant progress has been made toward improving the clinical outcome of other cancers, rates of mortality for OC are essentially unchanged since 1980, suggesting the need of new approaches to identify and characterize the molecular mechanisms underlying pathogenesis and progression of these malignancies. In addition, due to the low response rate and the high frequency of resistance to current treatments, emerging therapeutic strategies against OC focus on targeting single factors and pathways specifically involved in tumor growth and metastasis. To date, loss-of-function screenings are extensively applied to identify key drug targets in cancer, seeking for more effective, disease-tailored treatments to overcome lack of response or resistance to current therapies. We review here the information relative to essential genes and functional pathways recently discovered in OC, often strictly interconnected with each other and representing promising biomarkers and molecular targets to treat these malignancies.

Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors

“…Interestingly, high DOT1L expression has been shown to represent a biomarker of poor prognosis also in other gynecological malignancies, in particular ovarian cancer ( Zhang et al, 2017 ), where the expression of DOT1L has been associated with chemoresistance ( Liu D. et al, 2018 ) and shorter relapse-free (RFS) and overall (OS) survival ( Alexandrova et al, 2020 ; Chava et al, 2021 ). In a recent work by Cheasley et al, targeted sequencing identified DOT1L among putative driver genes mutated in low-grade serous ovarian carcinoma (LGSOC), which is characterized by a poor response to chemotherapy ( Cheasley et al, 2021 ).…”

A Review of the Clinical Characteristics and Novel Molecular Subtypes of Endometrioid Ovarian Cancer

“…Although high-grade EOVC and HGSOC have equally high response rates to platinum-based chemotherapy, high-grade EOVC seems to develop chemoresistance easily at recurrence, indicating the significance for novel therapeutics in this subtype ( 115 ). Approximately 60% of patients with EOVC may exhibit potential therapeutic targets based on the available reports ( 2 , 68 ).…”

“…Endometrioid ovarian cancer (EOVC) accounts for 10~15.8% of EOC ( 2 ), and shows an association with endometriosis ( 3 ) and Lynch syndrome ( 4 , 5 ). EOVC is often accompanied by synchronous endometrial carcinoma (EC) and typically diagnosed at an early stage ( 6 ).…”

Antitumoral Effect of Plocabulin in High Grade Serous Ovarian Carcinoma Cell Line Models

“…For decades, treatment of OC has consisted of surgery and systemic adjuvant or neoadjuvant chemotherapy with a carboplatin/paclitaxel regimen. However, despite achieving initial complete remission, about 80% of patients with advanced disease will relapse and finally progress to a platinum-resistant OC ( 1 ).…”