When your patient has one of the deadliest cancers of the lung, head, or neck, and there isn’t a single FDA-approved treatment that will help them, what do you do? For Jia Luo, MD, a medical oncologist at the Dana-Farber Cancer Institute, the answer is to dig deeper. Luo finds particular motivation for her research from her patients with NUT carcinoma, a rare but fast-growing cancer that often afflicts young people.

Luo’s K12 award through Harvard Catalyst has enabled her to conduct a first-in-human clinical trial–her first independent NIH-sponsored investigator-initiated trial–to test a promising combination therapy that emerged out of work from Stephen Elledge’s lab at Harvard Medical School (HMS). Luo, an assistant professor of medicine at HMS, is taking that work to the next level, with the goal of developing the first approved treatment for NUT carcinoma.

This feels like a body of work that could be a poster child for translational research. Tell me how the translational approach fits into this.

Through decades of work in the lab, we currently understand the biological underpinning of NUT carcinoma. We know it’s driven by a fusion of specific oncogenes, and we know that alone is sufficient to lead to this cancer. We’ve taken what we understand from this basic research in the lab–that CDK4/6 inhibition and BET inhibition is synergistic in this cancer–and translated it into this therapeutic trial in the clinic. If successful, this treatment may get approved for this patient population.

We are also collecting patient samples during the study to bring back to the lab to understand how we can do better. Why do some people respond and others do not? If someone stops responding, why does that happen? Translational experiments to answer these questions will help develop even more effective treatments for this cancer in the future.

“You see these patients in the clinic and some of them do well for years, but for others, nothing is approved or nothing works. It’s really motivating to be involved with laboratory collaborators to understand why this happens and design treatments that will hopefully help people with these cancers in the future.”

Being a medical oncologist and a clinical investigator is such a privilege. You see these patients in the clinic and some of them do well for years, but for others, nothing is approved or nothing works. It’s really motivating to be involved with laboratory collaborators to understand why this happens and design treatments that will hopefully help people with these cancers in the future.

You’re tackling a specific, uncommon carcinoma with a clear causal mechanism. Are there implications for this work beyond this rare aggressive form of cancer?

Absolutely. There’s good preclinical evidence that the class of inhibitors that we are studying may help other cancers that are more common, including prostate, breast, and BRD4-amplified cancers. In fact, this first-in-human study allows enrollment of people with these other cancers. Additionally, anything that we learn about one fusion oncogene-driven cancer can be applied to other cancers.

We published a recent paper summarizing the totality of evidence that NUT carcinoma should be classified as an aggressive subset of squamous cell cancer, a difficult-to-treat and much more common form of lung, head, and neck cancer. Learning from this will also help develop future therapies for squamous cancers.

How does this fit into the broader world of cancer research and where it is moving?

We’re understanding that cancer is many diseases, and treatment will require developing rational combination trials to tackle each of these differently. So instead of making a key and trying it on every single lock, contemporary cancer research says let’s craft the best key for this particular subset of locks.

“Being able to take a discovery from the very beginning in the lab through getting it approved as medicine that helps patients is what’s so incredibly exciting about this career.”

Developing synergistic combinations that are effective with few side effects is where the overall field of oncology treatment is headed. This project, which involves testing combination therapy is positioned very well in that sense.

Was this the first clinical trial that you led?

I have led several other industry-sponsored clinical trials. What’s unique about the K12-funded clinical trial is that it’s investigator-initiated. What that means is we wrote the trial. We’re designing it. We’re tracking all the participants. We have complete control over the data – it’s very powerful to be able to study the primary data. Especially with all the basic science expertise concentrated within our research ecosystem or in less common cancer populations, investigator-led studies can improve the ability to enroll the right patients and simultaneously study the biology to more efficiently develop better treatments for these individuals. The K12 grants the time to conduct an investigator-initiated trial to tackle an uncommon cancer in a stepwise scientific manner.

Where do you see yourself going in the future?

I would love to be a clinical investigator who develops effective treatments through leading and conducting trials and engaging with labs on translational research. This project could lead to a registrational clinical trial and to the first FDA-approved treatment for NUT carcinoma. Being able to take a discovery from the very beginning in the lab through getting it approved as medicine that helps patients is what’s so incredibly exciting about this career.