A groundbreaking study led by Dr. Li Chuanyun from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (CAS), has revealed a surprising double-edged role of human-specific genes. These genes, once celebrated for their role in human brain evolution and cognitive abilities, have now been found to be hijacked by cancers to promote tumor growth.
Published this week in Cell Genomics, the study uncovers how 37 genes, which emerged de novo—from previously non-coding DNA rather than duplication of existing genes—play a pivotal role not only in human development but also in cancer biology.
“These genes were essential to the evolution of the human brain,” said Dr. Li. “But cancer has learned to weaponize them.”
By analyzing a vast dataset of 120 mammalian genomes, 1,900 human transcriptomes, and 100 million protein spectra, researchers identified these uniquely human genes, normally active only during early development in the brain and testes. However, when they examined more than 5,000 tumor samples from 22 different cancer types, they found that nearly half of these genes are aberrantly reactivated in tumors, often via extrachromosomal circular DNA (ecDNA).
Functional experiments using CRISPR-Cas9 and siRNA confirmed that 57% of these genes directly fuel tumor cell proliferation. Their presence was also linked with poorer patient outcomes.
“This is evolution’s gamble,” said Dr. Li. “The same genes that helped us become intelligent are now liabilities. But we’re using this vulnerability to develop new treatments.”
The team focused particularly on two genes, ELFN1-AS1 and TYMSOS, which are absent in all non-human species and inactive in healthy adult tissues. Their selective reactivation in tumors makes them ideal therapeutic targets.
In collaboration with Dr. Cheng Qiang of Peking University, the team developed mRNA vaccines designed to teach the immune system to recognize and attack tumors expressing these genes. In humanized mouse models, the vaccines triggered strong anti-tumor immune responses—especially when paired with existing immunotherapies. Tests on human immune cells also showed promising antigen-specific responses.
“These genes have been overlooked by cancer research because they’re missing from standard animal models and were mislabeled as non-functional in genomic databases,” explained co-senior author Dr. An Ni. “Now, we recognize them as a bridge between our evolutionary past and future cancer therapies.”
The study, supported by the Chinese Academy of Sciences and the National Natural Science Foundation of China, opens up a new frontier in oncology—leveraging human evolution itself to fight cancer.
