A Model for the Moonshot?

OncLive Chairman,

Mike Hennessy

Turning around any ship of state, particularly one as large and unwieldy as the oncology research establishment, is always going to be a slow-moving and laborious undertaking. Yet changes are coming in that paradigm, as evidenced by the cover story in this issue, “The RAS Chase: Gaining Ground Against the Toughest Oncogene.” The article presents an overview of what may yet turn out to be one of National Cancer Institute (NCI)’s most vital initiatives.

Three years ago, Harold Varmus, MD, who was then director of the NCI, decided not to accept the conventional wisdom that the RAS oncogene, believed to be mutated in more than 30% of human cancers, was simply “undruggable.”

So he carved $10 million out of a tight budget and created a collaborative project to increase the fundamental knowledge base about RAS and its cancer-promoting activities. It’s the hard but utterly necessary work of basic science.

Now we’re seeing some of the first results of this work. There’s a more detailed, more precise roadmap of the RAS signaling network and a more accurate bank of the gene mutations in the pathway. Most notably, perhaps, there’s a new protein for use in experiments that can better replicate RAS activity than the model currently in use. It stands to reason that progress can’t be made without the right tools. Thus far, however, the past 35 years of RAS research seem to have been built on shifting sands rather than solid ground.

The RAS Initiative already seems to be building a far more solid foundation. This collaborative effort offers an intriguing example of what research leadership can accomplish at a time when we’re hearing some lofty talk about the National Cancer Moonshot Initiative, whose goal is to “end cancer as we know it today.”

Some observers have rightly pointed out that cancers are such heterogeneous diseases that it is misleading to even talk about it in the language employed by Moonshot boosters.

Yet if there really were a knockout blow that could be delivered in oncology, we couldn’t think of a better way to do that than to find a way to attack mutated RAS. As always, thank you for reading.