From the Guidelines
Cancer develops through a multistep process involving genetic and epigenetic alterations that disrupt normal cellular function, leading to uncontrolled growth and the potential to invade surrounding tissues and spread to distant sites through metastasis. The pathophysiology begins with mutations in critical genes that control cell growth, division, and death, as noted in studies such as 1, which highlights the role of genetic mutations in cancer development. These mutations may occur in proto-oncogenes, which become hyperactivated oncogenes that drive excessive cell proliferation, or in tumor suppressor genes, which normally restrict cell growth but lose their protective function when mutated. DNA repair genes may also be damaged, leading to genomic instability and accelerated mutation accumulation, a concept supported by research like 1, which discusses the processes of tumor initiation and progression in lung cancer.
Key aspects of cancer pathophysiology include:
- Genetic alterations: Mutations in genes controlling cell growth, division, and death, as discussed in 1 and 1.
- Epigenetic alterations: Changes in gene expression without altering the DNA sequence, such as methylation or acetylation, mentioned in 1.
- Hallmark capabilities of cancer cells: Sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis pathways, as outlined in the example answers.
- Tumor microenvironment: Cancer cells often reprogram their energy metabolism and recruit normal cells to create a supportive environment, as noted in the example answers.
The specific mutations and altered pathways vary widely among different cancer types, explaining the diverse behaviors and treatment responses observed clinically, a point emphasized across various studies including 1 and 1. Understanding these variations is crucial for developing effective treatment strategies tailored to the specific characteristics of each cancer type.
From the Research
General Pathophysiology of Cancer
The general pathophysiology of cancer involves a complex series of genetic and epigenetic changes that ultimately lead to uncontrolled cell growth and tumor formation.
- Cancer development is a multi-step process that requires the sequential acquisition of mutations in genes responsible for maintaining genomic integrity, as well as the activation of oncogenes and the inactivation of tumor suppressor genes 2.
- The process of carcinogenesis can be divided into at least three stages: initiation, promotion, and progression, with each stage involving distinct molecular and cellular changes 3, 4, 5.
- Initiation involves an irreversible genetic alteration, such as a mutation or deletion in DNA, while promotion involves reversible changes in gene expression mediated through promoter-receptor interactions 5.
- Progression is characterized by karyotypic instability and malignant growth, and is often associated with the inactivation of tumor suppressor genes and the activation of oncogenes 3, 5.
Key Molecular Targets
Critical molecular targets during the stages of carcinogenesis include:
- Proto-oncogenes and cellular oncogenes, which can be activated by mutations or other genetic alterations 5.
- Tumor suppressor genes, which can be inactivated by mutations or epigenetic changes, such as DNA methylation or histone modification 3, 6.
- MicroRNAs, which can regulate gene expression and contribute to cancer development and progression 6.
Epigenetic Changes
Epigenetic changes, such as DNA methylation, histone modification, and non-coding RNA expression, can also play a crucial role in cancer development and progression 6.
- These changes can modify gene expression and contribute to the activation of oncogenes and the inactivation of tumor suppressor genes.
- Epigenetic changes can also influence the epithelial-mesenchymal transition, a process that can contribute to cancer metastasis 6.
Metastasis
Metastasis requires a series of complex cellular and molecular changes, including: