Embracing cancer complexity: Hallmarks of systemic disease

Area of Science:

• Oncology
• Molecular Biology
• Systems Biology

Background:

• The "hallmarks of cancer" framework advanced understanding of carcinogenesis.
• However, molecular mechanisms of systemic effects and cancer mortality causes remain unclear.
• Elucidating tumor-host interactions is vital for cancer prevention and treatment.

Purpose of the Study:

• To discuss cancer as a systemic disease.
• To highlight key factors influencing cancer progression and outcomes.
• To propose future research directions for molecular oncology.

Main Methods:

• Review and synthesis of current knowledge on cancer as a systemic disease.
• Discussion of tumor-host interactions, including microenvironments, aging, metabolism, and the microbiome.
• Emphasis on the need for model systems incorporating human genetic variation.

Main Results:

• Cancer involves complex systemic interactions beyond the primary tumor.
• Factors like aging, metabolism, obesity, cachexia, circadian rhythms, nervous system, thrombosis, and microbiome significantly impact cancer.
• Gene-environment interactions are critical for understanding cancer's systemic nature.

Conclusions:

• A comprehensive understanding of cancer requires viewing it as a systemic disease.
• Future advances depend on integrating molecular oncology with systemic factors.
• Model systems with human genetic variation are essential for deciphering cancer mechanisms and improving patient outcomes.