Abstract
Ovarian cancer (OC) accounts for more than 150,000 deaths worldwide every year. Patients are often diagnosed at an advanced stage with metastatic dissemination. Although platinum- and taxane-based chemotherapies are effective treatment options, they are rarely curative and eventually, the disease will progress due to acquired resistance. Emerging evidence suggests a crucial role of long non-coding RNAs (lncRNAs) in the response to therapy in OC. Transcriptome profiling studies using high throughput approaches have identified differential expression patterns of lncRNAs associated with disease recurrence. Furthermore, several aberrantly expressed lncRNAs in resistant OC cells have been related to increased cell division, improved DNA repair, up-regulation of drug transporters or reduced susceptibility to apoptotic stimuli, supporting their involvement in acquired resistance. In this review, we will discuss the key aspects of lncRNAs associated with the development of resistance to platinum- and taxane-based chemotherapy in OC. The molecular landscape of OC will be introduced, to provide a background for understanding the role of lncRNAs in the acquisition of malignant properties. We will focus on the interplay between lncRNAs and molecular pathways affecting drug response to evaluate their impact on treatment resistance. Additionally, we will discuss the prospects of using lncRNAs as biomarkers or targets for precision medicine in OC. Although there is still plenty to learn about lncRNAs and technical challenges to be solved, the evidence of their involvement in OC and the development of acquired resistance are compelling and warrant further investigation for clinical applications.
Highlights
Ovarian cancer (OC) is the fifth most lethal cancer in women and accounts for more than 150,000 deaths annually worldwide [1]
These functions are executed through the long non-coding RNAs (lncRNAs) directly or indirectly influence on the transcription of various proteins, which can lead to contextdependent oncogenic or tumor-suppressive properties
Another approach to identifying homologous recombination (HR) deficiency was performed based on scores of the copy number alterations (CNA) profile of tumors, named “genomic scars,” which was very high in HGSC, and correlated to Poly (ADP-ribose) polymerase (PARP) inhibitors or platinum-based chemotherapy sensitivity [67]
Summary
Ovarian cancer (OC) is the fifth most lethal cancer in women and accounts for more than 150,000 deaths annually worldwide [1]. Inhibitors of Poly (ADP-ribose) polymerase (PARP) proteins are often used as second-line treatment for recurrent disease, mainly in patients with BRCA mutations. A recent randomized phase 3 trial performed in patients with a germline BRCA mutation has shown that the addition of oral PARP inhibitor (Olaparib) as maintenance therapy after chemotherapy prolongs the median progression free survival (PFS) by at least 3 years [9]. Despite the comprehensive combination of chemotherapy and maintenance treatment with targeted therapies, most patients develop resistance to treatment. The knowledge of the underlying molecular mechanisms involved in the development of resistance to chemotherapy is crucial for treatment decisions and the discovery of novel anticancer drug targets. Several cancer types have been associated with dysregulated expression of lncRNAs [18]
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