Tumorigenicity

Tumorigenicity is the ability of a biological specimen—such as a cell, tissue, or genetically modified construct—to form tumors. In cancer biology, it describes the capacity of cells to initiate and sustain tumor growth when introduced into a suitable host, typically an immunocompromised mouse. It is a key parameter in evaluating cancer-forming potential and is studied alongside proliferation, invasion, and metastasis. Tumorigenicity differs from oncogenicity; the former refers to actual tumor formation, whereas oncogenicity refers to the capacity to cause cancer through transforming events.

In research and development contexts, tumorigenicity assays are used to assess the safety of cell therapies, gene therapies, and stem cell products. Pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) can form teratomas when transplanted into animals, which can confirm pluripotency but also represent a risk in clinical applications. Teratoma formation assays and other in vivo tests, often in immunodeficient mice, estimate the likelihood and latency of tumor formation.

Mitigation strategies aim to reduce tumorigenicity in therapeutic products. These include differentiating cells to lineage-committed progenitors before transplantation, purifying out undifferentiated cells, using non-integrating or self-inactivating vectors for gene delivery, and incorporating genetic safety switches or suicide genes to eliminate aberrant cells.

Regulatory oversight typically requires characterization of tumorigenic risk, standardized testing, and defined acceptable limits before clinical use. Limitations of tumorigenicity testing include species differences, variable microenvironments, and the ethical and logistical constraints of long-term in vivo studies. Negative results do not guarantee safety, and risk assessment combines in vitro assays, in vivo tests, and product-specific considerations.