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Laboratory and phase I studies of new cancer drugs
P Workman1, S B Kaye, G Schwartsmann
1CRC Department of Medical Oncology, University of Glasgow, UK.
Abstract:
New drug discovery continues to follow the time-honored paths of screening and novel target identification combined with analogue development and serendipity. The agents selected here reflect these various approaches. They include drugs already showing significant antitumor activity, eg, anthrapyrazoles, temozolomide, camptothecin analogues, and taxotere, and updated information is provided on their development. Other drugs just entering or currently in phase I trials include rhizoxin, which seems capable of overcoming multidrug resistance; the novel bioreductive agent EO9 [corrected]; and bryostatin, a highly potent protein kinase C agonist. Sequence specificity could well prove to be an important factor in the development of DNA-interactive agents, and information is provided on the progress with distamycin mustard and the new cyclopropylpyrroloindole analogues carzelesin and adozelesin.
Insights
This study reviews novel anticancer drugs, including anthrapyrazoles, temozolomide, and taxanes, highlighting their development and potential. It also covers emerging agents like rhizoxin and bryostatin, focusing on overcoming drug resistance and novel mechanisms of action.
Area of Science:
- Oncology
- Pharmacology
- Drug Discovery
Background:
- Traditional drug discovery relies on screening, target identification, analogue development, and serendipity.
- Antitumor drug development is advancing with novel agents and strategies.
- Understanding drug resistance mechanisms is crucial for effective cancer treatment.
Purpose of the Study:
- To provide an overview of promising new anticancer drugs in development.
- To highlight agents with significant antitumor activity and novel mechanisms.
- To discuss the progress of drugs entering clinical trials, including those overcoming multidrug resistance.
Main Methods:
- Review of existing and emerging anticancer agents.
- Inclusion of drugs in various stages of development, from preclinical to Phase I trials.
- Focus on agents with demonstrated antitumor activity and unique properties.
Main Results:
- Several drug classes show significant antitumor activity, including anthrapyrazoles, temozolomide, camptothecin analogues, and taxotere.
- Emerging agents like rhizoxin demonstrate potential in overcoming multidrug resistance.
- Novel bioreductive agents (EO9) and protein kinase C agonists (bryostatin) are entering early trials.
- Progress in DNA-interactive agents, such as distamycin mustard and cyclopropylpyrroloindole analogues (carzelesin, adozelesin), is noted, emphasizing sequence specificity.
Conclusions:
- The landscape of anticancer drug discovery is diverse, incorporating established and novel approaches.
- Emerging therapies show promise in addressing challenges like multidrug resistance and targeting specific DNA interactions.
- Continued research and development are essential for advancing cancer treatment options.