Big ideas are all around us. They pop into our heads when we least expect it and consume our minds until we take steps to make them happen. That’s how research begins, continues, and evolves.
At Dana-Farber, scientists are attacking cancer at every level. Researchers go through a continuous cycle of experimentation to see the potential of an idea and how it can improve lives.
There are three types of medical research: clinical, translational, and basic. Each one has a part in transforming ideas into clinical care from the lab bench to the patient’s bedside and back again.
What is basic research?
You might think of basic research as the place to answer fundamental scientific questions for which we need answers. This is where you build a foundation for your ideas.
“Basic research is curiosity-driven research,” says Milka Kostic, Program Director, Chemical Biology at Dana-Farber Cancer Institute. “Think of that moment when an apple fell on Isaac Newton’s head. He thought to himself, ‘Why did that happen?’ and then went on to try to find the answer. That’s basic research.”
Basic medical research is usually conducted by scientists with a doctorate degree in fields such as biology and chemistry, among many others. They study the core building blocks of life — DNA, cells, proteins, molecules, etc. — to answer questions about their structures and how they work.
For example, oncologists now know that mutations in DNA enable the unchecked growth of cells in cancer. A scientist conducting basic research might ask: How does DNA work in a healthy cell? How do mutations occur? Where along the DNA sequence do mutations happen? And why?
“Some of the questions we have before or after clinical trials bring us back to basic research to understand more about what we are missing,” says Jia Luo, MD, a Dana-Farber clinical investigator who specializes in lung cancer at the Lowe Center for Thoracic Oncology. “Is there a new angle to attack this cancer from? Why is this treatment helping this group of people and not another?”
To investigate these questions, tissue or blood samples from animals or people may be used to provide answers. Sometimes the answer can be surprising.
“My work with a gene that, when mutated, causes lung cancer — called Kirsten rat sarcoma virus (KRAS) — is a discovery that arose from basic research. In the 1960s, we didn’t know how or why cancers grow. It was a shock then when it was discovered through basic research on cancer causing viruses that you only need one mutated gene, in this case RAS, to drive cancer cell growth. After discovering mutated KRAS, we could not target it for decades with drugs.
It was yet another series of basic science discoveries in the past decade that led to the finding of druggable pockets in the mutant KRAS protein. Luo adds that these are just starting to be exploited to turn KRAS off and stop sending signals that supercharge cell growth. “Thanks to basic research, we now have two US FDA approvals in KRAS mutated lung cancer alone, with many promising treatments being tested in clinical trials,” Luo adds.
What is clinical research?
Clinical research explores whether new treatments, medications, and diagnostic techniques are safe and effective in patients. Clinical research also encompasses quality improvement projects that seek to iteratively advance existing clinical care.
A classic example of clinical research is a clinical trial testing a promising treatment. In these clinical trials, eligible patients take a treatment and are carefully monitored to evaluate the treatment’s safety and potential side effects, as well as efficacy, or measurable benefit. If an early clinical trial is successful, it will be advanced to larger groups of patients to further study efficacy or even be randomized to standard of care to see if it should get U.S. Food and Drug Administration (FDA) approval and replace standard of care.
“A clinical trial is an enormous team effort. It involves taking a treatment with a lot of promise from basic research and seeing if it helps people,” says Luo. “We have research teams that help our investigators develop new trial ideas and other teams that are overseen by the clinical trial principal investigator to make sure the trial conduct adheres to its protocol.”
After a trial is complete, it is a team effort to analyze the data and determine whether we need to go back to the drawing board with what we learned or advance the treatment to the next phase of testing, Luo adds.
Another common area of clinical research involves coming up with a hypothesis based on clinical observation and/or basic research and addressing that by studying patient datasets. For example, in Luo’s work with KRAS-driven lung cancer, she found that certain subsets did not respond well to immunotherapy even though it’s the standard of care. This clinical observation led Luo and her team to think about how to better identify these patients and design clinical trials for these patients.
Translational research
When Luo and her team brought their KRAS study back to the lab, they looked at a cohort of individuals at Dana-Farber who have this cancer. “We are continuously asking questions about how to help people based on their response to the treatment in this kind of research,” Luo says.
“We saw fewer immune cells were going into these cancers, which would suggest why these people wouldn’t respond as well to immunotherapy,” Luo says. “This is a key observation that will impact how we design clinical trials for these patients.”
Translational research provides a bridge between research types by bringing specialists together to refine and advance a discovery. It provides a crucial link between clinical research and basic research. Investigators take this time to explore how a trial’s results can inform design of even better treatments or how basic research can be used to design a clinical trial.
As another example, Luo is the principal investigator of a first in human clinical trial of a combination of two drugs for a cancer called NUT carcinoma. The basis of this trial was due to the modest performance of one of the drugs in clinical trials when tested alone, which led Luo and her colleagues back to basic research to find a more potent combination.
Now that a new version with two drugs is back in the clinic, Luo hopes that this years-long path of accumulated knowledge and iterative translation of clinical to basic and back again will soon lead to a breakthrough.
“Translational research is a two-way street,” says Kostic. “There is always conversation flowing in both directions. It’s a loop, a continuous cycle, with one research result inspiring another.”