Faculty, Staff and Student Publications

Publication Date

3-28-2024

Journal

Cell

DOI

10.1016/j.cell.2024.02.009

PMID

38552609

PMCID

PMC12077170

PubMedCentral® Posted Date

5-14-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

The last 50 years have witnessed extraordinary developments in understanding mechanisms of carcinogenesis, synthesized as the hallmarks of cancer. Despite this logical framework, our understanding of the molecular basis of systemic manifestations and the underlying causes of cancer-related death remains incomplete. Looking forward, elucidating how tumors interact with distant organs and how multifaceted environmental and physiological parameters impinge on tumors and their hosts will be crucial for advances in preventing and more effectively treating human cancers. In this perspective, we discuss complexities of cancer as a systemic disease, including tumor initiation and promotion, tumor micro- and immune macro-environments, aging, metabolism and obesity, cancer cachexia, circadian rhythms, nervous system interactions, tumor-related thrombosis, and the microbiome. Model systems incorporating human genetic variation will be essential to decipher the mechanistic basis of these phenomena and unravel gene-environment interactions, providing a modern synthesis of molecular oncology that is primed to prevent cancers and improve patient quality of life and cancer outcomes.

Keywords

Humans, Carcinogenesis, Microbiota, Neoplasms, Obesity, Quality of Life

Published Open-Access

yes

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