Pharmacogenomics

Microrna-137 Downregulates Mcl1 in Ovarian Cancer Cells and Mediates Cisplatin-Induced Apoptosis

Cancer genetics and response to oncolytic virus treatment for ovarian cancer

Ovarian cancers (OCs) are often defined as poorly immunogenic tumors that have low response rates to current immunotherapies and frequently develop resistance to chemotherapies. Oncolytic viruses (OVs) are an emerging therapeutic approach that is favored due to its multifactorial mechanism of action; OVs aim to enhance immune cell recovery and infiltration into the tumor, in addition to assisting the immune system to identify and target evasive tumors. While many different OVs have been studied, this review focuses on the four that have been extensively tested in preclinical models and clinical trials with OC patients: vaccinia viruses, vesicular stomatitis virus, herpes simplex 1, and adenoviruses. We will first explore how these viruses have been developed, modified and tested as monotherapies in OCs, with limited success. The various combinatorial approaches involving OVs that are currently being investigated to improve the outcomes for OC patients will then be addressed. Attention will be given to how the genetics of OC cells may influence response to OVs and how that has led to genetic modifications of OVs that improve the cancer specificity and efficacy of these therapies.

Poly-(ADP-ribose) Polymerase Inhibitors: Paradigm Shift in the First-Line Treatment of Newly Diagnosed Advanced Ovarian Cancer

Debulking surgery associated with chemotherapy represent the backbone of ovarian cancer therapy. Adding bevacizumab has improved survival. Recently, PARP inhibitors were added in the first line as maintenance treatment for the patients who achieve a complete or partial response. These drugs act by blocking the activity of the PARP enzyme responsible for base-excision repair, and have shown positive responses when used for tumors lacking homologous recombination. Olaparib, niraparib and veliparib were evaluated and showed an increase in the duration of progression-free survival: 22.1 months (hazard ratio [HR] = 0.59), 13.8 (HR = 0.62) and 23.5 (HR = 0.68) with olaparib, niraparib and veliparib, respectively. This review describes the benefit of PARP inhibitors as maintenance therapy and discusses the efficacy according to breast cancer gene and homologous recombination status.