Can natural selection and druggable targets synergize? Of nutrient scarcity, cancer, and the evolution of cooperation

Area of Science:

• Evolutionary biology
• Cancer research
• Metabolic pathways

Background:

• Cancer therapy traditionally targets specific molecules, but cellular evolution presents a significant challenge.
• Cellular cooperation is fundamental to multicellularity and symbiosis, often linked to nutrient scarcity and chemiosmotic metabolism.

Purpose of the Study:

• To explore how understanding the breakdown of cellular cooperation can synergize with targeted cancer therapy approaches.
• To investigate the role of metabolic state (chemiosmotic vs. fermentative) in cellular cooperation and its implications for cancer.

Main Methods:

• Review and synthesis of existing knowledge on cellular cooperation, metabolism, and evolution in various organisms.
• Analysis of mammalian cancers as models of unicellular, glycolytic, and fast-replicating entities.
• Discussion of potential therapeutic strategies targeting the metabolic milieu to potentiate targeted treatments.

Main Results:

• Nutrient scarcity and chemiosmotic metabolism appear to favor cellular cooperation.
• Nutrient abundance and fermentative metabolism may signal a breakdown of cooperation, mirroring cancer's behavior.
• Mammalian cancers exhibit characteristics analogous to unicellular organisms with glycolytic metabolism.

Conclusions:

• A deeper understanding of the evolutionary breakdown of cellular cooperation, influenced by metabolic state, is crucial for advancing cancer therapy.
• Manipulating the metabolic environment holds promise for enhancing the efficacy of targeted therapeutics.
• Novel therapeutic avenues, such as the plant product avicins, warrant further investigation.