Origin of cancer disease
Pro Research Analysisby 
Searched over 200M research papers
Consensus Meter
Understanding the Origin of Cancer Disease
Evolutionary Transitions and Metabolic Origins of Cancer
The origin of cancer can be traced back to significant evolutionary transitions. One theory posits that cancer may originate from the major evolutionary transition from simple to complex cells, specifically when eukaryotic cells with glycolytic energy production merged with oxidative mitochondria. This transition enabled cells to obtain higher energy levels, which is crucial for the development of multicellular organisms. A decline in NAD+ and ATP levels, which are essential for cellular energy, is also implicated in the root causes of cancer. Restoring redox homeostasis and reactivating mitochondrial oxidative metabolism are considered important factors in cancer prevention.
Genetic Mutations and Somatic Changes
Cancer originates from a single cell that begins to behave abnormally due to somatic mutations. These mutations are changes in the genomic DNA caused by various mutational processes, including exposure to exogenous or endogenous mutagens, abnormal DNA editing, and failures in DNA repair mechanisms. For instance, specific mutational signatures, such as C:G>A:T transversions in smoking-associated lung cancer and C:G>T:A transitions in UV light-associated skin cancers, highlight the role of environmental factors in cancer development. These patterns of mutations provide insights into the mutational processes that cause human cancer.
Cellular Origin and Tumorigenesis
Identifying the specific cells and conditions that precede tumorigenesis is crucial for understanding and treating cancer. For example, research has shown that Barrett's esophagus (BE) originates from the gastric cardia, and esophageal adenocarcinoma (EAC) arises from undifferentiated BE cells. This highlights the importance of mapping the transcriptional landscape of healthy tissues to understand the origins of cancer. Additionally, different subtypes of cancer within an organ may derive from distinct 'cells of origin,' which acquire the first genetic hits that initiate cancer. Identifying these target cell populations can lead to earlier detection and better prediction of tumor behavior.
Historical and Genetic Perspectives
The genetic concept of cancer origin dates back to early observations of atypical cell divisions leading to chromosomal aberrations. These aberrations can result in abnormal growth, which is a hallmark of cancer. Over time, this concept has evolved with the understanding that somatic mutations play a significant role in cancer development. Studies on transmissible cancers, such as canine transmissible venereal tumor (CTVT), have further refined our understanding of cancer's genetic origins and evolution. CTVT, for instance, has been shown to be genomically stable despite massive karyotype abnormalities, indicating its adaptation to its niche over thousands of years .
Environmental and Epigenetic Factors
Environmental factors, such as radiation, diet, and viral infections, also play a significant role in cancer development. For example, the Chernobyl Nuclear Power Plant accident led to an increase in childhood thyroid cancer, illustrating the impact of radiation exposure. Additionally, viral infections, such as those caused by human herpesvirus 8, are linked to cancers like Kaposi's sarcoma. These factors, along with genetic mutations, contribute to the complex etiology of cancer.
Conclusion
The origin of cancer is multifaceted, involving evolutionary transitions, genetic mutations, and environmental factors. Understanding these diverse aspects is crucial for developing effective prevention, detection, and treatment strategies. By studying the molecular and cellular origins of cancer, researchers can uncover the underlying mechanisms that drive tumorigenesis and pave the way for personalized medicine and targeted therapies.
Sources and full results
Most relevant research papers on this topic