So far in this series, I’ve talked a lot about the biology of cancer treatment and recurrence. However, in my very first blog post, I invited you to join me on the road of drug development from bench (in the lab) to bedside (in a patient). You may have noticed I haven’t really lived up to that invite. In fact, besides a couple sentences here and there, I’ve barely talked about drug development at all (I wasn’t kidding when I said it was a long journey)! So, consider this our first proper stop on the drug development road as I answer the question: what exactly is a “precision medicine”?
At its core, precision medicine is an approach to treatment that uses information about an individual patient’s cancer to guide the care they receive. I think when people hear about precision medicine, they often think of a wonderfully futuristic world where every patient gets a bespoke treatment designed specifically for their cancer. While that is becoming a reality with some immunotherapies, most precision medicines today are matched to the tumour rather than made for the patient. So instead of using trial and error, we can test a tumour for a specific feature (also known as a biomarker) and match it to a drug we know can target it. But how do targeted treatments differ from traditional therapies like chemotherapy? You can think of chemotherapy as a sledgehammer, whereas targeted treatments are designed to act more like a fine chisel. Neither is automatically better than the other; they simply work in different ways. Under the precision medicine umbrella, there are many different types of targeted treatments, but the ones nearest and dearest to my heart are drugs called targeted small-molecule inhibitors.
Targeted small-molecule inhibitors are tiny compounds designed to interfere with specific proteins that cancer cells rely on to grow, survive or communicate. There are many different types of targets within a cell, and many different small-molecule inhibitors. But just this month, we had an incredible breakthrough with daraxonrasib, a brand new small-molecule inhibitor treatment approved by the U.S. Food and Drug Administration for metastatic pancreatic cancer. Daraxonrasib targets a family of proteins called rat sarcoma, or RAS for short (if the name gives you any clue, RAS was indeed discovered in rats). Normally, RAS works as an ON/OFF switch that helps cells respond to growth signals. In many cancers, including 90% of pancreatic cancer cases, RAS is mutated and becomes stuck in the ON position, leading to rapid and uncontrolled tumour growth. So, while daraxonrasib was not designed for one specific person, it was designed to target one specific biological problem.
While daraxonrasib does not mean pancreatic cancer is “solved” and it will not be the right treatment for every patient, it shows why precision medicine is so exciting. A treatment does not have to be custom-made for one person to be precise. It can be designed around a biological weakness shared by many tumours and used to specifically treat patients whose tumours carry that weakness. But of course, daraxonrasib didn’t begin its journey with successful trials. Most small-molecule treatments take years to develop before we actually hear about them in the news. Before they can even touch a patient, we have to work out how to create a tiny molecule that can actually bind to its target, block what it does and do so safely. Believe it or not, RAS was once considered an “undruggable” target!
So, how did we go from the undruggable to a successful treatment in patients? That is where the real journey of small-molecule drug development begins and is where we will head next.
Photo by Etactics Inc on Unsplash
