Developing new anti-cancer drugs: novel targets and methodological problems

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Cancer drug development has been transformed by understanding molecular events in cancer cells.
• Molecular profiling of cancer cell lines is crucial for identifying novel therapeutic targets.
• The National Cancer Institute (NCI) cell line screening program is central to modern cancer drug discovery.

Purpose of the Study:

• To review the challenges and strategies in the clinical development of biologically targeted anti-cancer therapies.
• To summarize pre-clinical and clinical data for specific classes of targeted anti-cancer drugs.
• To highlight the importance of 'proof-of-principle' studies in validating drug efficacy.

Main Methods:

• Utilizing molecularly characterized cancer cell lines for compound screening.
• Employing computer-based analysis of cytotoxicity response profiles.
• Reviewing pre-clinical and clinical data for targeted drug classes.

Main Results:

• Biologically targeted drugs are classified by specific targets or mechanisms of action.
• Clinical development necessitates studies confirming drug interaction with molecular targets.
• Data for cell-cycle modulators, signal transduction inhibitors, and proteasome inhibitors are presented.

Conclusions:

• Targeted anti-cancer therapies require rigorous molecular validation throughout development.
• Bridging pre-clinical findings with clinical outcomes is essential for successful drug approval.
• Future cancer drug development will continue to be driven by molecular insights.