Targeting multidrug resistance in cancer by natural chemosensitizers

Hamed, Ahmed R.; Abdel-Azim, Nahla S.; Shams, Khaled A.; Hammouda, Faiza M.

doi:10.1186/s42269-019-0043-8

Cited by 76 publications

(51 citation statements)

References 140 publications

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“…There are two main approaches in targeting ABC transporters as a means of overcoming chemoresistance: inhibition of their activity and inhibition of their expression. However, the first few generations of ABC transporters activity inhibitors were too toxic to be beneficial, lacked selectivity, or had an insufficient effect on drug accumulation [22]. Despite poor initial results, research in ABC transporter inhibitors is vigorously continuing.…”

Section: Tnbc Chemoresistancementioning

confidence: 99%

“…It not only inhibits ABCG2 activity but also accelerates its degradation [25]. Currently, a wide range of natural products are being tested as ABCG2 and ABCC1 activity inhibitors that can be safely combined with chemotherapy due to low toxicity [22]. Interestingly, tyrosine kinase inhibitors (TKIs), while substrates of ABC transporters at lower concentrations, serve as potent inhibitors (especially of ABCG2) at high concentrations [26].…”

Section: Tnbc Chemoresistancementioning

confidence: 99%

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Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge

Nedeljković

Damjanović

2019

Cells

601

458

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Triple-negative (TNBC) is the most lethal subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack of treatment options. Chemotherapy remains the standard of care for TNBC treatment, but unfortunately, patients frequently develop resistance. Accordingly, in recent years, tremendous effort has been made into elucidating the mechanisms of TNBC chemoresistance with the goal of identifying new molecular targets. It has become evident that the development of TNBC chemoresistance is multifaceted and based on the elaborate interplay of the tumor microenvironment, drug efflux, cancer stem cells, and bulk tumor cells. Alterations of multiple signaling pathways govern these interactions. Moreover, TNBC’s high heterogeneity, highlighted in the existence of several molecular signatures, presents a significant obstacle to successful treatment. In the present, in-depth review, we explore the contribution of key mechanisms to TNBC chemoresistance as well as emerging strategies to overcome them. We discuss novel anti-tumor agents that target the components of these mechanisms and pay special attention to their current clinical development while emphasizing the challenges still ahead of successful TNBC management. The evidence presented in this review outlines the role of crucial pathways in TNBC survival following chemotherapy treatment and highlights the importance of using combinatorial drug strategies and incorporating biomarkers in clinical studies.

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Section: Tnbc Chemoresistancementioning

confidence: 99%

Section: Tnbc Chemoresistancementioning

confidence: 99%

Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge

Nedeljković

Damjanović

2019

Cells

601

458

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“…Inhibition of efflux pumps can cause adverse effects in normal stem cells, since they exhibit high expression of several extrusion pumps which they need for their physiological function. In addition, ABCB1, and other pumps, play an essential role in keeping the integrity of the blood brain barrier, and interfering with their normal function could have negative consequences for the patient's health ( Figure 5B) (187,196,197).…”

Section: Targeting Molecules Involved In Drug Resistance: Abcb1 and Cd44mentioning

confidence: 99%

WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

et al. 2019

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WNT/β-catenin signaling is involved in many physiological processes. Its implication in embryonic development, cell migration, and polarization has been shown. Nevertheless, alterations in this signaling have also been related with pathological events such as sustaining and proliferating the cancer stem cell (CSC) subset present in the tumor bulk. Related with this, WNT signaling has been associated with the maintenance, expansion, and epithelial-mesenchymal transition of stem cells, and furthermore with two distinctive features of this tumor population: therapeutic resistance (MDR, multidrug resistance) and immune escape. These mechanisms are developed and maintained by WNT activation through the transcriptional control of the genes involved in such processes. This review focuses on the description of the best known WNT pathways and the molecules involved in them. Special attention is given to the WNT cascade proteins deregulated in tumors, which have a decisive role in tumor survival. Some of these proteins function as extrusion pumps that, in the course of chemotherapy, expel the drugs from the cells; others help the tumoral cells hide from the immune effector mechanisms. Among the WNT targets involved in drug resistance, the drug extrusion pump MDR-1 (P-GP, ABCB1) and the cell adhesion molecules from the CD44 family are highlighted. The chemokine CCL4 and the immune checkpoint proteins CD47 and PD-L1 are included in the list of WNT target molecules with a role in immunity escape. This pathway should be a main target in cancer therapy as WNT signaling activation is essential for tumor progression and survival, even in the presence of the anti-tumoral immune response and/or antineoplastic drugs. The appropriate design and combination of anti-tumoral strategies, based on the modulation of WNT mediators and/or protein targets, could negatively affect the growth of tumoral cells, improving the efficacy of these types of therapies.

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“…Since the different drug groups target various pathways, the chances of resistance to them decreases by using combination therapy (Bozic et al, 2013). For this purpose, during the past decades, many natural products which have chemosensitivity properties and derived from plants, animals, fungi, and microorganisms, have been identified for combination therapy (Hamed, Abdel‐Azim, Shams, & Hammouda, 2019; Khazaei Koohpar, Entezari, Movafagh, & Hashemi, 2015). Among phytochemicals, curcumin—due to its low toxicity, side effects, and influence on various cancers—has invited the attention of scientists.…”

Section: Introductionmentioning

confidence: 99%

Curcumin effect on cancer cells' multidrug resistance: An update

Keyvani‐Ghamsari

Khorsandi

Gul

2020

Phytotherapy Research

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Chemotherapy is one of the main methods for cancer treatment. However, despite many advances in the design of anticancer drugs, their efficiency is limited due to their high toxicity and resistance of cells to chemotherapeutic drugs. In order to improve the cancer therapy, it is essential to use the compounds that can overcome drug resistance and increase treatment efficiency. Researchers have studied the effects of natural compounds for the controlling various drug resistance mechanisms. Curcumin is a natural phenolic compound which shows potent anticancer activities in different tumors, alone or as an adjuvant with other antitumor drugs to prevent or inhibit the survival and cancer progression by various mechanisms. The role of curcumin in overcoming drug resistance was followed by reviewing different applications of curcumin in cancer therapy. Afterward, the clinical impacts of curcumin, role of curcumin in decreasing drug resistance in different cancer cells and its mechanisms were discussed. It has been demonstrated that curcumin regulates signaling pathways in cancer cells, reduces the expression of proteins related to drug resistance, and increases the performance of antitumor drugs at various levels. Curcumin reverses multidrug resistance mechanisms and increases sensitivity of resistance cells to chemotherapy. This review mainly focuses on different mechanisms of drug resistance and curcumin as a nontoxic natural substance to eliminate the effects of drug resistance through modulation and controlling cell resistance pathways and eventually suggests curcumin as a potent chemosensitizer in cancers.

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Targeting multidrug resistance in cancer by natural chemosensitizers

Cited by 76 publications

References 140 publications

Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge

Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge

WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

Curcumin effect on cancer cells' multidrug resistance: An update

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