New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer
2015
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Чланак у часопису (Објављена верзија)
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© 2015 Bentham Science Publishers
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Приказ свих података о документуАпстракт:
Resistance to chemotherapeautic drugs is one of the main obstacles to
effective cancer treatment. Multidrug resistance (MDR) is defined as
resistance to structurally and/or functionally unrelated drugs, and has
been extensively investigated for the last three decades. There are two
types of MDR: intrinsic and acquired. Tumor microenvironment selection
pressure leads to the development of intrinsic MDR, while acquired
resistance is a consequence of the administered chemotherapy. A central
issue in chemotherapy failure is the existence of heterogeneous
populations of cancer cells within one patient and patient-to-patient
variability within each type of cancer.
Numerous genes and pathways contribute to the development of MDR in
cancer. Point mutations, gene amplification or other genetic or
epigenetic changes all affect biological functions and may lead to the
occurrence of MDR phenotype. Similar to the characteristics of
cancerogenesis, the main features of MDR include abnormal tumor
vasculature, regions of hypoxia, aerobic glycolysis, and a lower
susceptibility to apoptosis. In order to achieve a lethal effect on
cancer cells, drugs need to reach their intracellular target molecules.
The overexpression of the efflux transporter P-glycoprotein (P-gp) in
MDR cancer cells leads to decreased uptake of the drug and intracellular
drug accumulation, minimising drug-target interactions.
New agents being or inspired by natural products that sucessfully target
these mechanisms are the main subject of this review. Two key approaches
in combating MDR in cancer are discussed (i) finding agents that
preserve citotoxicity toward MDR cancer cells; (ii) developing compounds
that restore the cytotoxic activity of classic anticancer drugs.
Напомена:
Related to: https://radar.ibiss.bg.ac.rs/handle/123456789/3882.
Кључне речи:
Cancer; Multidrug resistance; P-glycoprotein; Natural product drugs; Plant secondary metabolites; Marine productsИзвор:
Current Pharmaceutical Design, 2015, 21, 38, 5589-5604Финансирање / пројекти:
- Идентификација молекуларних маркера за предикцију прогресије тумора, одговора на терапију и исхода болести (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41031)
- COST Action CM1106 (Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells)
- COST Action CM1407 (Challenging organic syntheses inspired by nature - from natural products chemistry to drug discovery)
DOI: 10.2174/1381612821666151002113546
ISSN: 1873-4286
PubMed: 26429711