During the past five years, we’ve talked a lot about the idea of translating scientific findings from bench to bedside—to make discoveries in the lab that eventually help us more effectively treat patients with cancer.
Translational science has evolved from being a linear process to being more of an iterative, rational process of approaching a problem—from the bench-to-bedside-and-back.
Five years ago, [and this is generalizing of course] cancer biologists were less engaged in translating their work to clinical applications because all they heard about in the clinic was cytotoxic chemotherapy. Today, personalized, targeted therapies and rational combinations of drugs are on their way to becoming first-line treatment. These therapies and rational drug combinations stand firmly on the bedrock of cancer biology discoveries. Cancer biologists now have a tangible, immediate clinical application for their work, and it’s growing.
Cancer biologists and other basic scientists provide clinicians with fundamental research on the genes, proteins and pathways to target in cancer. They partner with us to identify the biomarkers that will tell us which patients will have the best outcomes to any given targeted therapy. And they are critical to the cancer treatment revolution I believe we’re in the midst of.
Collaboration and translational research is my focus in my new leadership role at the Cancer Center. My goal is to play matchmaker: to find opportunities for our members to work together toward a goal, and to bring people who might not know each other right now together to solve a particular problem. I’ll be going on rounds, so to speak, at all of our consortia sites to find out what our members there are working on and try to connect them with others.
I would like to set up small working groups to inform the clinical members about pathways or biomarkers that some groups are working on, and likewise to inform basic scientists about current clinical research approaches and how these can facilitate the translation of their own work. We want to promote these collaborations regardless of how differentiated someone is to the lab or the clinic, so that no one in the Cancer Center is working in a vacuum. We want to create an environment that greatly facilitates and promotes collaboration and translation.
Here’s an example from my own work:
In January, I attended our Molecular Oncology Program retreat in Boulder, and I found out that Xuedong Liu, PhD, an associate professor in the CU chemistry department, is working on a series of novel histone deacetylase inhibitors. I talked to him after his presentation about figuring out what biomarkers can be used to determine which colorectal cancer patients would benefit from these therapies when they go into clinical trials. These agents are interesting but to date there has not been a patient selective strategy applied to facilitate their development. Now, we’re collaborating on that project.
The new translational medicine is multidirectional.
One example is the ALK inhibitor story in lung cancer. The agent that targets ALK was initially tested in a phase I trial (“bedside”) without a specific mechanism of action (it was billed as a c-met inhibitor) and no predictive biomarker or plan for selecting patients, other than c-met amplification. During this early clinical development, lab studies (“bench”) revealed the mechanism of ALK inhibition, which was translated into a selective biomarker that was applied to the clinical trial (“bedside”). Through this intense collaboration among basic, translational, and clinical researchers, the drug is approaching Phase III trials to be used in ALK+ patients. In the past, this process could have taken years.
This iterative process is also being used in rational approaches to combination therapy.
James DeGregori, PhD and Joaquin Espinosa, PhD, co-leaders of the Cancer Center’s Molecular Oncology Program are using synthetic lethal screens to find the pathways cancers use to resist treatment. Even though the research is “basic” it has immediate clinical application when the screens identify other drugs we can combine with standard treatment to block pathways of resistance. This is actually being done by Chris Porter’s trial of dasatinib and cyclosporin A in patients with leukemia. Resistance is a clinical problem that bench scientists throughout the Cancer Center are partnering with clinicians on.
Our members shouldn’t have to develop novel agents in isolation. Collaboration among basic and translational scientists to identify novel pathways, drugs and biomarkers and among clinical researchers to develop novel approaches to clinical development will not only lead to better outcomes for patients, but will hopefully speed up the time the whole process takes.