Mechanisms of chemotherapy resistance in ovarian cancer

Abstract

Ovarian cancer is one of the most lethal gynecologic cancers. The standard therapy for ovarian cancer has been the same for the past two decades, a combination treatment of platinum with paclitaxel. Recently, the FDA approved three new therapeutic drugs, two poly (ADP-ribose) polymerase inhibitors (olaparib and niraparib) and one vascular endothelial growth factor inhibitor (bevacizumab) as maintenance therapies for ovarian cancer. In this review, we summarize the resistance mechanisms for conventional platinum-based chemotherapy and for the newly FDA-approved drugs.

Perspectives of metal-organic framework nanosystem to overcome tumor drug resistance

“…MDR in tumors is complex and multifactorial, including biological barrier formed by the tumor microenvironment (TME) [48][49][50][51][52][53] and overexpression of drug efflux transporter resulting in the inability to accumulate drugs intracellularly [40,[54][55][56][57] , the drug inactivation due to the specific environment of gene control and metabolism, the resistance to apoptosis and deoxyribonucleic acid (DNA) damage repair [58][59][60][61][62][63] , and immune evasion [64][65][66][67][68][69][70][71] , as shown in Figure 1.…”

“…Dense ECM is a distinctive feature of PDAC, but overexpression of drug efflux pumps is more prevalent in more cancer cells. The overexpression of drug efflux pumps is one of the essential mechanisms of MDR in cancer cells [50,52] , as various adenosine triphosphate (ATP)-binding cassette transporter family proteins are expressed on the cell membrane. Most of these proteins are ATP-driven multidrug efflux pumps such as MDR protein and P-glycoprotein (P-gp).…”

“…After the intracellular drug binds to the transporter on the cell membrane, ATP hydrolysis drives a conformational change and pushes the drug out of the cell, resulting in the inability of the intracellular drug to accumulate in sufficient quantities to kill the cells [73] . Ruan et al used nanocarriers to reverse drug resistance induced by overexpression of the drug efflux pumps by inhibiting mitochondrial ATP synthesis [52] . The cyclin-dependent kinase 6-phosphoinositide 3-kinase (CDK6-PI3K) signaling axis is an effective target for attenuating ATP binding cassette subfamily B member 1/P-gpmediated MDR in cancer cells [11,74,75] .…”

Long noncoding RNAs as therapeutic targets to overcome chemoresistance in ovarian cancer

“…Ovarian cancer is one of common malignancies in females ( Giaquinto et al, 2022 ; Siegel et al, 2022 ). The key obstacle for the therapy outcome is the development of drug resistance in ovarian cancer patients ( Ortiz et al, 2022 ). Genetic and epigenetic changes have been known to participate in chemotherapy resistance in a variety of cancers, including ovarian cancer ( Meng et al, 2021 ; Zhang et al, 2022 ; Zhao et al, 2022 ).…”

Editorial: Molecular influences in therapies in ovarian cancer

“…However, studies have demonstrated that therapies and treatments can be influenced by molecular mechanisms that need to be further studied. For example, several studies have found that an active therapeutic target for combination treatment was found to be the DNA damage response pathway, such as Poly (ADP-ribose) polymerase (PARP) ( 4 ).…”