Where did cancer come from
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Summary
10 papers analyzed
These studies suggest that cancer originates from a combination of genetic mutations, chronic infections, stem cells, evolutionary transitions, and cellular injuries.
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The Origins of Cancer: A Comprehensive Overview
Introduction to Cancer Origins
Cancer, a complex and multifaceted disease, originates from a single cell that begins to behave abnormally, dividing uncontrollably and invading adjacent tissues. This aberrant behavior is primarily due to somatic mutations—changes in the genomic DNA caused by various mutational processes. These processes include exposure to mutagens, DNA editing errors, and failures in DNA repair mechanisms.
Genetic Mutations and Cancer
The role of genetic mutations in cancer development is well-documented. For instance, the TP53 gene, commonly mutated in human cancers, shows distinct mutation patterns linked to specific carcinogens. Smoking-associated lung cancer often features C:G>A:T transversions, while ultraviolet light-associated skin cancers exhibit C:G>T:A transitions and CC:GG>TT:AA substitutions. These mutation patterns provide insights into the mutational processes driving cancer.
Stem Cells and Cancer
The concept that cancers arise from tissue stem cells has been a cornerstone of cancer research. Stem cells, which are essential for normal tissue renewal, can acquire genetic mutations that initiate cancer. This idea is supported by the observation that cancers can originate from different 'cells of origin' within an organ, each acquiring the initial genetic hits that lead to tumor formation. For example, gastric cancers have been shown to originate from bone marrow-derived cells (BMDCs) in response to chronic infection, progressing through stages of metaplasia and dysplasia to intraepithelial cancer.
Embryonal Rest Theory
The embryonal rest theory, proposed in the 19th century, suggests that cancers arise from dormant embryonic remnants in adult tissues. These remnants can be activated to become cancerous, a concept that has evolved to include the idea that adult tissue stem cells can give rise to cancer. This theory is supported by the similarity in cell signaling pathways between embryonic cells and cancer cells, indicating a possible link between the two.
Metabolic Disease Hypothesis
Another perspective on the origin of cancer is the metabolic disease hypothesis, which posits that cancer may stem from impaired energy metabolism. This theory suggests that the evolutionary transitions from simple to complex cells and from single-celled to multicellular organisms, which involved significant changes in energy production mechanisms, are at the root of cancer. Restoring mitochondrial oxidative metabolism and redox homeostasis are considered crucial for cancer prevention.
Prenatal Origins of Cancer
Recent research has highlighted the prenatal origins of some childhood cancers, linking driver mutations to embryonal and early postnatal development. This understanding has identified new therapeutic targets and strategies for early detection and prevention of childhood cancers.
Conclusion
The origins of cancer are multifaceted, involving genetic mutations, stem cell transformations, metabolic changes, and even prenatal factors. Understanding these diverse origins is crucial for developing effective prevention, detection, and treatment strategies. By continuing to explore the genetic, cellular, and metabolic underpinnings of cancer, researchers can uncover new ways to combat this complex disease.
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