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[Antitumor drug resistance and therapeutic approaches to reverse resistance]
Abstract:
Acquired multidrug resistance as well as innate drug resistance are directly related to ineffectiveness and failure of the cancer chemotherapy. The mechanisms of such resistance, especially those of innate resistance, have not been fully elucidated. Drug resistant tumor cells, however, usually bear biochemical changes which are related to resistance mechanisms. New modalities with high selectivity against resistant cells could, therefore, be possible if we could target these biochemical changes. Vincristine (VCR)-and adriamycin (ADM)-resistant tumor cells (pleiotropic drug resistant cells) usually show an enhanced outward transport of these antitumor agents, and they express unique glycoproteins in the plasma membrane. By targeting for these biochemical changes characteristic to the resistant tumor cells, we establish new modality which shows high selectivity against drug resistant tumor cells. In this review, I will describe genetic origin of drug resistance, biochemical mechanisms of drug resistance and reversal of drug resistance in tumor cells. The modality to utilize calcium channel blockers which inhibit the enhanced outward transport of VCR and ADM from resistant tumor cells will be reviewed.
Insights
Cancer chemotherapy often fails due to drug resistance. Targeting specific biochemical changes in resistant tumor cells, like enhanced outward transport, offers a new strategy to improve treatment effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Context:
- Cancer chemotherapy effectiveness is limited by acquired and innate drug resistance.
- Mechanisms underlying drug resistance, particularly innate resistance, remain incompletely understood.
- Drug-resistant tumor cells exhibit distinct biochemical alterations linked to resistance pathways.
Purpose:
- To explore the genetic and biochemical underpinnings of drug resistance in cancer.
- To review strategies for overcoming drug resistance in tumor cells.
- To highlight novel therapeutic modalities targeting biochemical changes in resistant cells.
Summary:
- Drug resistance in cancer chemotherapy leads to treatment failure.
- Resistant tumor cells often display enhanced outward transport of anticancer agents and express unique glycoproteins.
- Targeting these specific biochemical changes can lead to selective therapies against resistant cells.
Impact:
- Understanding drug resistance mechanisms can guide the development of more effective cancer treatments.
- Identifying unique markers on resistant cells allows for the design of targeted therapies.
- Exploring modalities like calcium channel blockers may reverse drug resistance and improve patient outcomes.