Dual attack with two existing drugs destroys lung cancer

Doctor holding a model of a lung
Understanding how lung tumors survive and grow leads to an innovative new treatment.
Lung cancer is now the leading cause of cancer death in the United States, responsible for almost 160,000 deaths each year.

Many are driven by the KRAS oncogene. KRAS is an essential gene, but in its mutant form, it is an important step in the generation of many types of cancer.

For over 30 years, the KRAS oncogene has been a focus of research. Finding a way to remove its teeth would be pivotal in the treatment of a range of cancers.

As part of this effort, rather than targeting the gene directly, some scientists have focused on pathways that are related to the errant gene.

One pathway of interest centers on insulin and insulin-like growth factor-1 (IGF-1). This pathway helps to regulate the uptake of nutrients into the cell, providing it with the energy and raw ingredients it needs to grow.

If the tumor cell’s fuel supply could be severed, its onward march might be halted. However, it is not clear whether KRAS oncogenes are reliant on this particular pathway, and, in clinical trials, results have not been encouraging.

In fact, one study in mice found that lung tumors actually became more aggressive after the pathway was suppressed.

Attacking KRAS-related pathways
Undeterred, a team from the Boston Children’s Hospital in Massachusetts used a fresh approach. In the mouse study mentioned above, the insulin/IGF-1 signaling pathway was only partially closed off. In the latest study, though, a genetic technique was used that shut it down entirely.

To do this, the scientists crossed two strains of genetically modified mice. The first is a well-used model for KRAS-driven lung cancer, and the other is a mouse used to study diabetes that lacks insulin/IGF-1 signaling.

In the diabetes mouse model, the insulin/IGF-1 pathway is unshackled by the deletion of two genes: Irs1 and Irs2. These encode “adaptor” proteins, which are essential for the smooth running of the insulin1 pathway.

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