tumorprogression

Tumor progression refers to the process by which a neoplasm advances from a relatively indolent state toward increased malignant potential, ultimately enabling sustained growth, invasion of surrounding tissues, and possibly metastasis. Progression is driven by accumulating genetic and epigenetic alterations and by selective pressures within the tumor microenvironment, and it typically occurs over time through clonal evolution rather than a single event.

Key capabilities acquired during progression include sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, induction of angiogenesis, and activation of invasion and metastasis. Additional changes involve genetic instability, metabolic reprogramming, and immune evasion. These traits are described as hallmarks of cancer.

Genetic and epigenetic changes accumulate in a branched, heterogeneous manner within a tumor. Driver mutations confer growth advantage, while passenger mutations accumulate. Clonal evolution and selective sweeps generate intratumoral diversity, influencing response to therapy and likelihood of progression. Common pathways implicated include p53, RB, and PI3K/AKT/mTOR signaling, along with RAS/MAPK, WNT, and others.

Models of progression emphasize gradual accumulation of alterations and Darwinian selection under pressures such as hypoxia, nutrient availability, and treatment. Well known examples include the colorectal adenoma-carcinoma sequence and similar multistep processes in other organ systems. Metastasis reflects a later phase of progression, though some tumors exhibit early dissemination.

Clinical relevance includes estimation of prognosis and selection of treatment. Progression-free survival, tumor grade, and stage reflect progression status. Therapeutic resistance often arises through ongoing evolution, leading to relapse. Pseudoprogression can complicate assessment in some therapies.

Understanding tumor progression informs prevention, monitoring, and therapeutic development, including strategies to target clonal heterogeneity, the tumor microenvironment, and specific driver pathways. Ongoing research seeks to map the order of alterations and identify interventions that can interrupt progression or prevent metastasis.