Role of ABCB1 in mediating chemoresistance of triple-negative breast cancers

Abstract

Triple negative breast cancer (TNBC) is a group of breast cancers which neither express hormonal receptors nor human epidermal growth factor receptor. Hence, there is a lack of currently known targeted therapies and the only available line of systemic treatment option is chemotherapy or more recently immune therapy. However, in patients with relapsed disease after adjuvant or neoadjuvant therapy resistance to chemotherapeutic agents has often developed, which results in poor treatment response. Multidrug resistance has emerged as an important mechanism by which TNBCs mediate drug resistance and occurs primarily due to overexpression of ABC transporter proteins such as P-glycoprotein (Pgp). Pgp overexpression had been linked to poor outcome, reduced survival rates and chemo-resistance in patients. The aim of this mini review is to provide a topical overview of the recent studies and to generate further interest in this critical research area, with an aim to develop an effective and safe approach for overcoming Pgp mediated chemo-resistance in TNBC.

A comparative study of the ability of recombinant oncolytic adenovirus, doxorubicin and tamoxifen to inhibit the proliferation of breast cancer cells

“…The effects of these two treatments are not satisfactory for patients with cancers that are the most difficult to treat such as those with triple-negative breast cancer (MDA-MB-231). 14,15,16 Over recent years, there has been significant development in biomedicine and genetic engineering technology; consequently, many new treatment options have been developed, including immunotherapy and gene therapy. Oncolytic viruses are viruses that can selectively infect and replicate in tumour cells.…”

Carnosine Potentiates Doxorubicin-Induced Cytotoxicity in Resistant NCI/ADR-RES Cells by Inhibiting P-Glycoprotein—In Silico and In Vitro Evidence

“…Resistance of the cancer cell to chemotherapy exaggerates the problem of increased cancer-associated mortality and morbidity [ 1 ]. The increased expression and activity of P-gp diminishes drug delivery to cellular targets and increases the MDR of cancers [ 2 , 4 , 5 ]. Indeed, clinical evidence implicates P-gp with therapy failure and poor prognosis [ 7 , 8 ].…”

“…One important mechanism by which cancer cells resist cytotoxic drugs is increasing the expression of specific efflux pumps that shuttle organic molecules to the outside of the cell across the plasma membrane, preventing their intracellular accumulation to cytotoxic levels and ultimately leading to therapeutic failure [ 2 , 3 ]. These transmembrane efflux pumps include P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) family of transporters that are associated with cancer drug resistance [ 4 , 5 ]. Thus, targeting these transporters would increase treatment efficacy and decrease cancer-associated mortality [ 3 ].…”

“…Contrarily, the expression and function of such transport systems largely determine the susceptibility of cancer cells to chemotherapeutic agents [ 2 , 3 ]. The increased expression and/or activity of P-gp, encoded in humans by the ABCB1 gene, confers resistance to anticancer drugs [ 4 , 5 ]. Clinically, tumors overexpressing P-gp are more resistant to chemotherapy and correlate with poor patient prognosis [ 7 , 8 ].…”

siRNA targeting ABCB1 potentiates the efficacy of chemotherapy in human triple-negative breast cancer cells

“…With ATP hydrolysis, these proteins act as drug effluxers and pump a broad range of antineoplastic agents from the cytosol to the outside of the cell, resulting in MDR. In this way, the intracellular accumulation of anticancer drugs is reduced below the required level for cell killing, thereby leading to low therapeutic efficacy [16,17]. ABCB1, also known as permeability glycoprotein (P-gp) or MDR1, is the first and most well-identified member of the ABC transporters [13,18].…”