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 (MDR) has emerged as an important mechanism by which TNBCs mediate drug resistance and occurs primarily due to overexpression of ATP-binding cassette (ABC) transporter proteins such as P-glycoprotein (Pgp). Pgp overexpression had been linked to poor outcome, reduced survival rates and chemoresistance 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 the aim to develop an effective and safe approach for overcoming Pgp-mediated chemoresistance in TNBC.
Highlights
Breast cancer is the most common cause of cancer-related deaths in women [1]. It is a heterogeneous group of cancers currently most commonly categorized into four main types according to immunohistochemical profile and increasingly confirmed by gene expression profile testing: (1) Luminal A which is positive for estrogen receptor (ER) and progesterone receptor (PR) and negative for epidermal growth factor receptor 2 (HER-2) receptor and low Ki67; (2) Luminal B which is positive for ER and sometimes HER-2 and low or negative for PR with a high Ki67; (3) HER-2 positive tumors that are HER-2 positive and negative for ER and PR; (4) triple-negative breast cancer (TNBC) which is negative for ER, PR, and HER-2 expression
Derived drug resistance can be observed in tumors that exhibit poor initial response to chemotherapy without prior exposure to anti-cancer agents, while, the acquired type can be seen in tumors that demonstrates an initial good response to treatment followed by adaptation and resistance to the drug treatment, often resulting in a cancer type with a more aggressive behavior [8]
The drug transport depends on the activity of ATP-binding cassettes (ABC superfamily) which is membrane transporter proteins that pump the chemotherapeutic drug outside the cell
Summary
Breast cancer is the most common cause of cancer-related deaths in women [1]. It is a heterogeneous group of cancers currently most commonly categorized into four main types according to immunohistochemical profile and increasingly confirmed by gene expression profile testing: (1) Luminal A which is positive for estrogen receptor (ER) and progesterone receptor (PR) and negative for epidermal growth factor receptor 2 (HER-2) receptor and low Ki67; (2) Luminal B which is positive for ER and sometimes HER-2 and low or negative for PR with a high Ki67; (3) HER-2 positive tumors that are HER-2 positive and negative for ER and PR; (4) triple-negative breast cancer (TNBC) which is negative for ER, PR, and HER-2 expression. The drug transport depends on the activity of ATP-binding cassettes (ABC superfamily) which is membrane transporter proteins that pump the chemotherapeutic drug outside the cell. P-glycoprotein (Pgp) is a member of ABC-B subfamily and is known to play a crucial role in mediating multidrug resistance (MDR) in cancer [19].
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