The article introduces a novel genetic engineering approach called selection gene drives to proactively combat the challenge of drug resistance in cancer treatment. This system is designed to redirect tumor evolution by modifying cancer cells with a dual-switch genetic circuit. The first switch provides a controllable fitness advantage under targeted therapy, promoting the engineered cells' expansion, while the second switch is a therapeutic payload that, when engaged, eliminates both the engineered and native drug-resistant cells via a bystander effect. Through the use of stochastic and spatial evolutionary models, the researchers established the necessary design criteria for this system, demonstrating in both in vitro and mouse models that this forward-engineering strategy can successfully eradicate diverse forms of pre-existing genetic resistance in tumors. The work highlights the modularity of the design and its potential to be a powerful framework for future evolution-guided anticancer therapy.

References:

• Leighow S M, Reynolds J A, Sokirniy I, et al. Programming tumor evolution with selection gene drives to proactively combat drug resistance[J]. Nature Biotechnology, 2025, 43(5): 737-751.