ABC Transporters in Human Diseases: Future Directions and Therapeutic Perspectives

Falguières, Thomas

doi:10.3390/ijms23084250

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…In addition to reduced drug uptake, drug efflux mediated by the overexpression of ABC transporters is the major mechanism contributing to insufficient intracellular drug concentration. In humans, the ABC transporter superfamily consists of 49 members categorized into 7 subfamilies (ABCA–ABCG) functioning to transport various substrates, including lipids, ions, peptides, and xenobiotics 116 . The involvement of ABC transporters in MDR was first discovered in 1976 when ABCB1, which is also known as P ‐glycoprotein ( P ‐gp) or multidrug resisitance 1 (MDR1) protein, was discovered in mouse MDR cell lines 117 .…”

Section: Resistance Mechanisms In Cancer and Combating Strategiesmentioning

confidence: 99%

“…In humans, the ABC transporter superfamily consists of 49 members categorized into 7 subfamilies (ABCA–ABCG) functioning to transport various substrates, including lipids, ions, peptides, and xenobiotics. 116 The involvement of ABC transporters in MDR was first discovered in 1976 when ABCB1, which is also known as P ‐glycoprotein ( P ‐gp) or multidrug resisitance 1 (MDR1) protein, was discovered in mouse MDR cell lines. 117 To date, at least 13 ABC transporters have been found to directly mediate chemoresistance via the efflux of anticancer drugs.…”

Section: Resistance Mechanisms In Cancer and Combating Strategiesmentioning

confidence: 99%

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Understanding and targeting resistance mechanisms in cancer

Lei

Teng

Wurpel

et al. 2023

MedComm

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Resistance to cancer therapies has been a commonly observed phenomenon in clinical practice, which is one of the major causes of treatment failure and poor patient survival. The reduced responsiveness of cancer cells is a multifaceted phenomenon that can arise from genetic, epigenetic, and microenvironmental factors. Various mechanisms have been discovered and extensively studied, including drug inactivation, reduced intracellular drug accumulation by reduced uptake or increased efflux, drug target alteration, activation of compensatory pathways for cell survival, regulation of DNA repair and cell death, tumor plasticity, and the regulation from tumor microenvironments (TMEs). To overcome cancer resistance, a variety of strategies have been proposed, which are designed to enhance the effectiveness of cancer treatment or reduce drug resistance. These include identifying biomarkers that can predict drug response and resistance, identifying new targets, developing new targeted drugs, combination therapies targeting multiple signaling pathways, and modulating the TME. The present article focuses on the different mechanisms of drug resistance in cancer and the corresponding tackling approaches with recent updates. Perspectives on polytherapy targeting multiple resistance mechanisms, novel nanoparticle delivery systems, and advanced drug design tools for overcoming resistance are also reviewed.

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Section: Resistance Mechanisms In Cancer and Combating Strategiesmentioning

confidence: 99%

Section: Resistance Mechanisms In Cancer and Combating Strategiesmentioning

confidence: 99%

Understanding and targeting resistance mechanisms in cancer

Lei

Teng

Wurpel

et al. 2023

MedComm

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The transport activity of the multidrug ABC transporter BmrA does not require a wide separation of the nucleotide-binding domains

Di Cesare,

Kaplan,

Rendon

et al. 2024

Journal of Biological Chemistry

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The Role of TAMs in the Regulation of Tumor Cell Resistance to Chemotherapy

McWhorter,

Bonavida

2024

Crit Rev Oncog

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Tumor-associated macrophages (TAMs) are the predominant cell infiltrate in the immunosuppressive tumor microenvironment (TME). TAMs are central to fostering pro-inflammatory conditions, tumor growth, metastasis, and inhibiting therapy responses. Many cancer patients are innately refractory to chemotherapy and or develop resistance following initial treatments. There is a clinical correlation between the level of TAMs in the TME and chemoresistance. Hence, the pivotal role of TAMs in contributing to chemoresistance has garnered significant attention toward targeting TAMs to reverse this resistance. A prerequisite for such an approach requires a thorough understanding of the various underlying mechanisms by which TAMs inhibit response to chemotherapeutic drugs. Such mechanisms include enhancing drug efflux, regulating drug metabolism and detoxification, supporting cancer stem cell (CSCs) resistance, promoting epithelial-mesenchymal transition (EMT), inhibiting drug penetration and its metabolism, stimulating angiogenesis, impacting inhibitory STAT3/NF-κB survival pathways, and releasing specific inhibitory cytokines including TGF-β and IL-10. Accordingly, several strategies have been developed to overcome TAM-modulated chemoresistance. These include novel therapies that aim to deplete TAMs, repolarize them toward the anti-tumor M1-like phenotype, or block recruitment of monocytes into the TME. Current results from TAM-targeted treatments have been unimpressive; however, the use of TAM-targeted therapies in combination appears promising These include targeting TAMs with radiotherapy, chemotherapy, chemokine receptor inhibitors, immunotherapy, and loaded nanoparticles. The clinical limitations of these strategies are discussed.

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ABC Transporters in Human Diseases: Future Directions and Therapeutic Perspectives

Cited by 3 publications

References 35 publications

Understanding and targeting resistance mechanisms in cancer

Understanding and targeting resistance mechanisms in cancer

The transport activity of the multidrug ABC transporter BmrA does not require a wide separation of the nucleotide-binding domains

The Role of TAMs in the Regulation of Tumor Cell Resistance to Chemotherapy

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