Cancer Pathophysiology

The fundamental abnormality driving the onset and progression of all cancer types is the dysregulated proliferation of cells that grow and divide in an uncontrolled manner, invade normal tissues and organs, and ultimately disseminate throughout the body. This loss of growth control arises from the progressive accumulation of abnormalities across diverse regulatory systems, producing the typical hallmarks that distinguish malignant from healthy cells.

Historically, cancer has been conceptualized as a multistep, Darwinian process driven by genetic mutations and selection of clones with increasing capacities for proliferation, survival, invasion, and metastasis. Tumor initiation is thought to stem from an initial genetic alteration that disrupts normal proliferation and produces a clonally derived population of aberrant cells. Subsequent genetic and functional heterogeneity emerge as additional mutations accumulate during tumor progression, fueling continuous clonal selection and adaptation.

More recent discoveries have expanded this paradigm. Epigenetic dysregulation, chromatin remodeling, and alterations in the noncoding RNA landscape (including microRNAs, lncRNAs, circRNAs, and others) have been shown to significantly impact both tumor initiation and progression. Moreover, modern technological advances—including single-cell profiling, spatial transcriptomics, proteogenomics, and high-resolution imaging—have revealed new layers of complexity in tumor ecosystems, highlighting previously unrecognized drivers of cancer behavior.

This section of Cancers seeks to publish high-quality contributions that address the full spectrum of cancer pathophysiology. We invite submissions of original research articles, systematic and narrative reviews, and communications that report novel findings and significant advances in the biological mechanisms underlying both solid and hematologic cancers.

Topics of interest include the following:

• Cancer biology and genetics:
• Oncogenes, tumor suppressor genes, and genetic drivers of cancer
• Genome instability, including chromothripsis, kataegis, and structural variants
• Cancer-associated mutations and clonal evolution
• Cancer epigenetics and non-coding RNAs:
• Epigenetic reprogramming in tumor initiation and progression
• Alterations in non-coding RNAs (miRNAs, lncRNAs, circRNAs) and their roles in regulating cancer pathways
• Chromatin remodeling and  3D genome organization in cancer
• Cancer metabolism and tumor microenvironment:
• Metabolic rewiring in tumors (Warburg effect, nutrient sensing, and metabolic symbiosis)
• Cancer–stroma interactions
• Tumor microenvironment and immunometabolism
• Tumor–immune interactions:
• Tumor–immune co-evolution, immune escape, and immune editing
• Myeloid reprogramming, tumor-associated macrophages, and immune cell dynamics
• Immune checkpoint inhibition and tumor immunotherapy resistance mechanisms
• Tumor evolution:
• Tumor clonal architecture and intratumoral heterogeneity
• Phenotypic plasticity and lineage switching (e.g., epithelial–mesenchymal transition and neuroendocrine differentiation)
• Cancer stem cells, minimal residual disease, and mechanisms of relapse and dormancy
• Metastasis and Invasion:
• Mechanisms of metastatic spread and organotropism
• Tumor angiogenesis and the role of the vasculature in metastasis
• Physical forces, mechanotransduction, and mechanobiology in tumor invasion
• Emerging Technologies and Therapeutic Strategies:
• Single-cell genomics, spatial transcriptomics, and proteogenomics for cancer profiling
• Targeted therapies, synthetic lethality, and personalized approaches
• Organoids, organ-on-chip models, and other in vitro platforms
• Computational oncology and AI-driven approaches to uncover new cancer vulnerabilities