What is pre-cancer and why is it important?
- mudra choudhury
- Jan 16, 2024
- 3 min read
Written by Mudra Choudhury
01.16.2024
Pre-cancer is a critical stage in the continuum of cancer development, warranting closer scrutiny for its implications in cancer prevention and early intervention. The concept of pre-cancer was rigorously defined at the 2004 National Cancer Institute-sponsored Conference on Precancer, as elaborated in the publication "Precancer: A Conceptual Working Definition: Results of a Consensus Conference" by Berman et al. (Cancer Det. And Prev., 2006). This definition encompasses five criteria: an association with an increased risk of cancer, origin from within the precancerous cells, distinctiveness from normal and cancerous tissue, identifiable molecular and phenotypic characteristics, and diagnosability.
Recognizing pre-cancer is pivotal because most cancers have an identifiable pre-cancer stage. Accurate identification and early intervention at the pre-cancer stage could revolutionize cancer treatment, shifting the focus from conventional therapies like chemotherapy to proactive cancer prevention strategies.
Experts in the field contribute significant insights into this area. Shelley Hwang of Duke University discusses that most precancers are identifiable. For example, they usually appear to have histological abnormalities characteristic of the pre-cancer stage, although they may show limited progression potential. James Reading from the University College of London is exploring the role of T-cells in early cancer detection and their alterations during early carcinogenesis. He is interested in investigating whether these immune cells can be utilized for pre-cancer detection. Finally, Manuel Serrano from the Cambridge Institute of Science and Altos Labs highlights the correlation between aging, cellular senescence (a state where cells are dysfunctional and inflammatory), and cancer risk. He states that aging and cancer are linked to an increase in senescent cells in the tissue microenvironment. Therefore, he points to senolytic drugs (those that kill senescent cells) as a promising avenue for therapeutic development.
With the emergence of large-scale omics data, many current studies are now focused on identifying the molecular factors that lead to the development of cancer from precancerous stages. This research often varies depending on the type of cancer, as the underlying molecular pathways can differ between tissues. To exemplify this, I have referenced two studies that have examined precancerous lesions in the lungs.
In lung cancer research, the study "Evolution of DNA Methylome from Precancerous Lesions to Invasive Lung Adenocarcinomas" by Hu et al. (Nat Commun, 2021), investigates the role of DNA methylation patterns in cancer progression. DNA methylation refers to the process by which a methyl group is added to the DNA molecule, which can affect downstream biological pathways without changing DNA sequence. This study identifies specific differentially methylated regions (DMRs) that change as cancer develops, indicating their potential role in the early stages of carcinogenesis.
Another study, "Evolutionary Proteogenomic Landscape from Pre-Invasive to Invasive Lung Adenocarcinoma" by Zhang et al. (Cell Rep Med, 2024), employs a comprehensive proteogenomic analysis to delineate the molecular changes occurring from pre-invasive to invasive stages. This research exemplifies the utility of multi-omics approaches in elucidating the complex evolution of cancer from its precursors.
While these studies yield novel and important findings in pre-invasive lung cancer, a pressing question in pre-cancer research is the existence of common pathways or mechanisms across different tissue types that could lead to universal therapeutic strategies. Identifying such cross-tissue markers of pre-cancer could facilitate the development of broad-spectrum cancer prevention therapies.
The Pre-Cancer Atlas project represents a significant endeavor in this direction. This initiative aims to compile a comprehensive repository of molecular data on known precancers, encompassing genomic, transcriptomic, and epigenetic profiles. Although still in development, this atlas could be instrumental in uncovering novel biomarkers for pre-cancer and shaping the future landscape of cancer prevention and treatment.
In summary, the study of pre-cancer is not merely an academic exercise but a crucial step towards a paradigm shift in cancer management. It opens up the possibility of addressing cancer in its nascent stages, potentially transforming the approach to cancer prevention and care.
Citations:
Berman et al. "Precancer: A Conceptual Working Definition: Results of a Consensus Conference." Cancer Detection and Prevention, 2006. [https://doi.org/10.1016/j.cdp.2006.09.002]
Hu, X., Estecio, M.R., Chen, R. et al. "Evolution of DNA Methylome from Precancerous Lesions to Invasive Lung Adenocarcinomas." Nature Communications, 12, 687, 2021. [https://doi.org/10.1038/s41467-021-20907-z]
Pre-cancer: From diagnosis to intervention opportunities. Cancer Cell 41 (2023) [https://www.cell.com/cancer-cell/pdf/S1535-6108(23)00085-5.pdf]
Srivastava et al. “PreCancer Atlas: Present and Future.” Cancer Prev. Res. (2023) [https://doi.org/10.1158/1940-6207.CAPR-22-0435]
Zhang et al. "Evolutionary Proteogenomic Landscape from Pre-Invasive to Invasive Lung Adenocarcinoma." Cell Reports Medicine, Vol 5, Issue 1, 2024. [https://doi.org/10.1016/j.xcrm.2023.101358]
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