How did cancer originate
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Understanding the Origins of Cancer
Single-Cell Origin and Somatic Mutations
Cancer originates from a single cell that begins to behave abnormally, dividing uncontrollably and invading adjacent tissues. This aberrant behavior is due to somatic mutations—changes in the genomic DNA caused by various mutational processes. These processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms. For instance, specific mutational patterns, such as C:G>A:T transversions in smoking-associated lung cancer and C:G>T:A transitions in ultraviolet light-associated skin cancers, have been linked to known carcinogenic influences like tobacco and UV light.
Genetic and Epigenetic Modifications
All cancers arise from normal cells whose progeny acquire cancer-initiating mutations and epigenetic modifications, leading to tumorigenesis. The identity of these "cells-of-origin" has been a subject of extensive research. Genetically engineered mouse models (GEMMs) have been instrumental in understanding how various naive cellular compartments can initiate tumors in vivo. These models have shown that multiple lineages within a given organ can generate tumors with similar histopathology. This understanding is crucial for identifying target cell populations for early detection and preventive therapies.
Evolutionary and Metabolic Perspectives
The origin of cancer can also be viewed through the lens of life's major evolutionary transitions. The first transition involved the merger of glycolytic eukaryotic cells with oxidative mitochondria, while the second transition saw the evolution from single-celled to multicellular organisms. These transitions, along with the decline of NAD+ and ATP levels, are considered fundamental to the development of cancer. Restoring redox homeostasis and reactivating mitochondrial oxidative metabolism are important factors in cancer prevention.
Prenatal and Early Postnatal Origins
Some childhood malignancies are believed to arise from postnatally persistent embryonal cells. Recent research has strengthened the links between driver mutations and early developmental stages, identifying important therapeutic targets and strategies for early detection and prevention of childhood cancer.
Historical and Theoretical Perspectives
The genetic concept of cancer origin dates back to early 20th-century theories, which suggested that atypical cell divisions and chromosomal aberrations could lead to cancer. This idea has evolved to include both genetic and epigenetic theories, with current research focusing on multistage cancer development and the role of cancer stem cells .
Conclusion
Understanding the origins of cancer involves a multifaceted approach, encompassing genetic mutations, epigenetic modifications, evolutionary biology, and early developmental processes. Identifying the specific cells and conditions that precede tumorigenesis is crucial for developing effective prevention, early detection, and treatment strategies.
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