Complexity against current cancer research: Are we on the wrong track?

Area of Science:

• Oncology
• Systems Biology
• Genomics

Background:

• Cancer genetics and genomics have yielded key concepts like proto-oncogenes, tumor suppressors, driver/passenger genes, and tumor heterogeneity.
• Advances in spatial and single-cell genomics allow reconstruction of tumorigenesis trajectories and improved patient stratification.
• Despite progress, translating discoveries into targeted therapies remains limited, primarily to kinase inhibitors.

Purpose of the Study:

• To critique the current "monogenic" disease model of cancer research, which overlooks patient individuality and complexity.
• To advocate for a systems cancer approach focusing on reconstructing altered information networks within individual tumors.
• To propose a shift towards individualized cancer therapy based on dynamic regulatory network analysis.

Main Methods:

• Reconstructing altered information networks in cancer using systems biology principles.
• Analyzing network hierarchies to identify druggable key nodes regulating aberrant information transfer.
• Integrating data from multinational, multidisciplinary efforts including clinicians and various biological/computational experts.
• Developing dynamic regulatory networks for (patho)physiological conditions to model information flow.

Main Results:

• Current approaches may be misguided by seeking commonalities in "monogenic" models, ignoring significant interindividual variability.
• A systems approach can reveal critical nodes within altered cellular information networks.
• Individualized network analysis can guide the proposal of targeted combination therapies.

Conclusions:

• A paradigm shift towards a systems and individualized approach is necessary for effective cancer research and therapy.
• Understanding and modeling the complex, altered information transfer in individual cancers is crucial.
• Multidisciplinary collaboration is essential to develop dynamic regulatory networks for personalized cancer treatment strategies.