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Pharmacological modulators of DNA-interactive antitumor drugs
Abstract:
The poor therapeutic index and limited efficacy of current cancer chemotherapeutic agents represent an important pharmacological problem. Although there has been a significant increase in our understanding of the mechanisms by which anticancer drugs kill mammalian cells, identification of new, effective anticancer agents during the last decade has been exceeding slow. Thus, attention has focused on understanding the causes of drug resistance and on either sensitizing tumor cells to existing anticancer agents using what could be called 'chemoenhancers', or protecting non-malignant tissues against serious untoward effects using 'chemoprotectors'. John Lazo and Robert Bahnson review recent strategies attempting to modulate the activity of antineoplastic drugs.
Insights
Current cancer chemotherapy has poor efficacy and a narrow therapeutic index. Researchers are exploring chemoenhancers to sensitize tumor cells and chemoprotectors to shield healthy tissues from chemotherapy side effects.
Area of Science:
- Pharmacology
- Oncology
- Drug Discovery
Background:
- Current cancer chemotherapeutic agents exhibit a poor therapeutic index and limited efficacy, posing a significant pharmacological challenge.
- Despite advances in understanding how anticancer drugs affect mammalian cells, the discovery of new, effective agents has been slow over the past decade.
Purpose of the Study:
- To review recent strategies for modulating the activity of antineoplastic drugs.
- To explore methods for overcoming limitations in cancer chemotherapy, focusing on drug resistance.
Main Methods:
- Review of recent scientific literature and strategies.
- Analysis of approaches to modulate antineoplastic drug activity.
Main Results:
- Focus has shifted towards understanding drug resistance mechanisms.
- Development of 'chemoenhancers' to sensitize tumor cells to existing drugs.
- Development of 'chemoprotectors' to mitigate adverse effects on non-malignant tissues.
Conclusions:
- Strategies to enhance existing chemotherapy are crucial due to the slow pace of new drug discovery.
- Modulating drug activity through chemoenhancers and chemoprotectors offers promising avenues for improving cancer treatment outcomes.