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Tyler Jacks, Cancer Moonshot Panel Co-Chair, Discusses Roadmap

Xconomy National — 

The Obama administration wants to speed up cancer research with its “Cancer Moonshot” program—packing 10 years’ worth of work on prevention and treatment programs into five is one of its rallying cries. Agreeing on what to do, and how to do it, is the first step. The FDA agreed this summer to reorganize the way it evaluates drugs, diagnostics, and other cancer-related products.

This week, a panel of 28 scientists presented the National Cancer Institute’s National Cancer Advisory Board a set of recommendations and national priorities for basic research, clinical trial practice, and drug development. In an interview with Xconomy, panel co-chair Tyler Jacks acknowledged the recommendations were broad, with many details yet to be worked out. (So broad, in fact, that they elicited no small amount of Internet eye-rolling, including this tweet Thursday from David Shaywitz, CMO of genomic data firm DNANexus.)

A set of recommendations for policies and reimbursement is forthcoming from a different moonshot group.

The scientific goals, writ large, included nationwide data sharing among researchers and health practitioners; better prevention through medicine (such as the HPV vaccine) and public education (anti-smoking campaigns); and a registry that could match cancer patients to trials based on genetics and other factors. (The full report is here; a summary is here.)

Xconomy reached Jacks, who is director of the Koch Institute for Integrative Cancer Research at MIT, after the panel made its presentation in Washington, DC, this week. The following is an edited, condensed version of our conversation.

X: The report starts by recommending a national cancer patient network. Is this akin to a nationwide study, like the government’s precision medicine initiative?

TJ: No, it’s not a national study or clinical trial. It’s characterization of individuals’ cancers, a way to apply analysis to patients all over the country. Included is the idea that when a patients signs up they’ll get better information about their own cancer—bringing the science to the patient—and better access to clinical trials. If you analyze the genome of a patient’s tumor, a mutation in gene X might make [the tumor] sensitive to drug Y. Once they’re in the system, you can get them onto a trial. It’s related to the MATCH trial being run by the National Cancer Institute.

X: It seems every day there are more examples of one mutation identified as the driver of a cancer. But is there a danger of relying too heavily just on genomics to determine the course of a patient’s treatment?

TJ: We know that existence of particular mutations can predict sensitivity to some drugs, but in some cases they don’t. And in many patients there are mutations without appropriate drugs. We’re going to need other biomarkers to indicate different treatment strategies, such as RNA expression or protein expression. Right now, getting the genomic profile is easiest. But at the end of the day [the network] will integrate other data types.

X: This sounds a lot like the GENIE project to pool patient data among seven top cancer centers.

Seven Major Cancer Centers To Pool Patients’ Gene, Health Data

TJ: Yes. This is another [initiative] to create systems to more effectively catalog the collection of mutations that exist. GENIE is one of several ongoing. The hope is that we can bring it to a broader array of patients.

X: Even among the GENIE members, there are varying levels of resources to build the data infrastructure, convert existing data, and pay for things like genomic tests. How will you implement this across the country?

TJ: Important new infrastructures will have to be built, for sure. There are policy issues. And who will pay for the genotyping of every patient?

X: You don’t think that sequencing prices will come down enough?

TJ: They certainly will come down and won’t be that expensive, but still somebody has to pay for them. Ultimately we’ll need to reach an agreement in Medicare/Medicaid and other payer systems that other forms of testing, once they’re demonstrated to be valuable and informative, will be covered.

X: “Valuable and informative”—those are key words. A top priority at GENIE is to show that decoding cancer genomes actually leads to better health outcomes. No one has ever done that.

TJ: The MATCH trial also wants to provide evidence to demonstrate that value. But yes, even now for a lot of patients, what we can do at the level of the genome will not lead to better outcomes. It would obviously be better for patients and for our whole healthecare system to be aligned on that, but we’re not there yet. These recommendations describe some scientific steps necessary, but they don’t try to solve the reimbursement question. We highlighted it as a barrier, but punted it to the task force that includes Vice President Biden and sits above our panel.

X: Your panel is recommending a separate clinical trial network for immunotherapy. Why?

TJ: We probably shouldn’t have described it that way. We’re actually proposing a scientific network to create better access to clinical materials. Immunotherapy is on fire, it’s taking over the field of cancer. This particular recommendation tries to improve our understanding why certain patients respond and others fail. What are the underlying mechanisms? Even PD1 expression [the protein on cancer cells that several approved drugs, called checkpoint inhibitors, target so that the tumor can’t hide from the patient’s immune system] is not a clear discriminator between responders and non-responders.

Immunologists feel the problem is much more complicated: Which cells are in the tumor microenvironment, what state they’re in, which proteins they’re expressing. There’s a lot of scientific inquiry, but we’re not doing it in a coordinated fashion. Academic groups are digging into the science but are under-resourced, and by and large not connected to the companies doing the trials. So let’s bring the scientists to the trials, whether industry or NCI-sponsored trials.

X: Let’s talk about cancer screening. The panel’s recommendation about prevention makes reference to screening for colorectal cancer but not for other cancer types. Is that because the usefulness of many other types of screening is in doubt?

TJ: I can’t say for sure why our working group had the focus on colorectal, but the data in support of colorectal screening is unimpeachable, and the screening is not as highly adopted as it needs to be. I like the example of Lynch syndrome, which is a genetic predisposition to colorectal cancer. As few as five percent of carriers know they’re carriers, and would really benefit from screening.

You’re right, with others it’s still uncertain—if not very uncertain—if there’s a public health benefit.

X: What about liquid biopsy and the quest for pan-cancer screening and early detection?

TJ: I expected it to be featured more prominently in the report but it’s not. It’s expected to have an impact, but it’s too early to say there will be an impact in the next five years [which is a big part of the moonshot recommendations].

X: There is also a call for more research into pediatric cancers, which are driven in large part by fusion oncoproteins. Why don’t we know much about them?

TJ: We know about them, but we don’t know how to deal with them. For some pediatric cancers, which tend to have “quiet” genomes with very few mutations, the fusion oncoproteins are one of few mutations you find. At the moment there are no drugs to target them. We gave it a lot of attention; it’s probably the most basic science of all the recommendations we have. It really is early days. This probably won’t be a new therapeutic opportunity in the next five years, but we were willing to make an exception.

Photo courtesy of MIT.