Is there a case for selectively promiscuous anticancer drugs?

Area of Science:

• Oncology and Systems Biology

Background:

• Molecularly targeted cancer therapies are a cornerstone of modern oncology.
• Tumor robustness and resilience observed through systems-level studies challenge single-target approaches.
• Current multipronged attacks, while addressing various cancer hallmarks, increase adverse events.

Purpose of the Study:

• To critically survey existing paradigms in molecularly targeted cancer therapy.
• To propose a new therapeutic strategy based on systems-level tumor observations.
• To address the growing concern of enhanced side effects in cancer treatment.

Main Methods:

• Critical review of current molecularly targeted cancer therapy paradigms.
• Analysis of systems-level observations on tumor robustness and resilience.
• Conceptual development of 'selective nonselectivity' as a therapeutic strategy.
• Proposal for drug redesign guided by molecular features that promote selectivity.

Main Results:

• Single-target paradigms are insufficient against robust and resilient tumors.
• Multipronged attacks enhance side effects, posing a clinical challenge.
• 'Selective nonselectivity' offers a potential alternative to single-target approaches.
• Rational control of drug specificity is crucial for mitigating side effects.

Conclusions:

• A shift from single-target to 'selective nonselectivity' may be necessary for effective cancer therapy.
• Drug redesign incorporating selectivity-promoting features is key to managing side effects.
• Systems-level understanding is vital for developing next-generation cancer treatments.