Breakthrough: First Genetically Engineered Cancer Model in Naked Mole Rats

Researchers at the H. Lee Moffitt Cancer Center have achieved a significant milestone by developing the first genetically engineered model of lung cancer in naked mole rats, a species renowned for its remarkable resistance to cancer and extended lifespan. Published in the journal Cancer Discovery, this study offers new insights into how cancer originates in these unique rodents and highlights potential parallels with human tumor development.

The team employed CRISPR gene-editing technology to introduce the Eml4-Alk fusion gene, a common driver of lung cancer in humans and mice. While this alteration induced tumors in mice, naked mole rats remained resistant unless additional genetic changes occurred. Tumors only formed when the EML4-ALK fusion was combined with the loss of tumor suppressor genes p53 and Rb1. Approximately 30% of the naked mole rats developed aggressive lung tumors resembling a rare human cancer subtype called pleomorphic carcinoma.

Dr. Joseph Kissil explained that multiple genetic events are necessary for cancer development in naked mole rats, similar to human cancers. This discovery provides a more accurate model to understand tumor initiation and progression. The tumors observed were diverse and infiltrated by immune cells such as T cells and macrophages, opening avenues for future research into tumor microenvironment and immune response.

Despite their higher resource requirements, naked mole rats hold promise as valuable models for uncovering new cancer prevention and treatment strategies. Dr. Kissil emphasized that creating genetically defined models is essential for translating biological insights into clinical benefits. This platform enables detailed study of early tumorigenic steps and may lead to novel therapeutic approaches for cancers like pleomorphic lung carcinoma, which currently lack targeted treatments.

This pioneering work not only advances our understanding of cancer resistance mechanisms but also enhances the potential for developing innovative therapies based on comparative biology.