Harnessing archaeogenetic for cancer therapy: bridging ancient DNA insights with modern therapeutic innovations

Cancer is not only a modern disease but an evolutionary condition shaped by long-term genetic and epigenetic changes. Research in archaeogenetics and ancient DNA (aDNA) provides new insights into how inherited mutations, viral elements, and environmental exposures have influenced cancer risk over thousands of years. This review explores how ancient genomic and epigenomic evidence contributes to understanding the origins of cancer and its relevance to modern clinical oncology. Evidence from skeletal and mummified remains confirms that malignancies existed long before industrialization. Ancient genomes reveal hereditary risk variants in cancer-related genes such as BRCA and TP53, suggesting that genetic susceptibility to cancer has deep evolutionary roots. Importantly, reconstructed DNA methylation patterns from ancient samples indicate that epigenetic regulation of tumor suppressor genes and oncogenic pathways has been conserved across time. Human endogenous retroviruses (HERVs), integrated into the human genome during evolution, show epigenetic activation in several cancers and may serve as potential biomarkers or therapeutic targets. Comparative analyses further demonstrate both stable mutational processes and environmentally influenced epigenetic shifts. Overall, integrating ancient epigenomic data with modern multi-omics approaches enhances our understanding of cancer biology. This evolutionary and epigenetic perspective may support biomarker discovery, improve risk stratification, and guide the development of targeted and immunotherapeutic strategies in precision oncology.