Unlocking Cancer’s Weakness: Targeting Transcriptional CDKs with Small Molecule Inhibitors

alondon
The intersection of traditional natural remedies and modern small-molecule drugs remains a compelling area of exploration. Photo: Pexels.com

By: Zhijia Wang

Suomennos: Syövän heikkouksien paljastaminen: Transkriptionaalisten CDK:iden kohdentaminen pienmolekyylisillä estäjillä

Cancer depends on uncontrolled gene expression regulated by transcriptional CDKs (CDK7, 9, 12). My PhD used oncology libraries and cell tests to find small molecule inhibitors against these kinases, seeking potential drugs for transcriptionally addicted cancers.

Finding the brakes for cancer growth: My PhD journey

In my research, I focus on small-molecule compounds that selectively inhibit transcriptional kinases in cancer cells—advancing the frontier of precision oncology. Photo: Pexels.com

Cancer is a disease that touches many lives. It happens when cells in the body start to grow out of control. Scientists are always looking for new ways to stop this growth. My PhD project has focused on understanding how cancer cells turn on the instructions (genes) they need to grow and spread. We’ve been looking for tiny molecules that can act like brakes on this process.

Understanding how cancer cells grow

Imagine cancer cells as cars with the accelerator pedal stuck down. They grow and multiply too quickly. Our bodies have ways to control this growth, but in cancer, these controls don’t work properly. One important way cells control growth is by deciding which instructions (genes) to follow. This process of turning genes “on” or “off” is called transcription. Certain proteins help with this process, and in cancer, some of these proteins become overactive.

Searching for clues: How we looked for potential cancer drugs

To find our “brakes,” we used a method like searching through a huge library of tiny building blocks called small molecules. We tested many different molecules to see if any of them could slow down the growth of cancer cells. This process is called screening, and it’s like trying out many different keys to see which one fits a lock. We used a special library focused on molecules that might work against cancer.

Putting drugs to the test: What happens when we treat cancer cells?

Once we found some promising molecules from our screening, we needed to test them more carefully. We used cancer cells grown in the lab to see exactly what these molecules did. We looked at several things:

  • Did the molecules kill the cancer cells? We checked if the number of cancer cells decreased after treatment.
  • Did the molecules stop the cancer cells from growing? We measured if the cells were still able to multiply.
  • Did the molecules make the cancer cells self-destruct? There’s a natural process called apoptosis where cells can break themselves down, and we wanted to see if our molecules could trigger this in cancer cells.

By doing these tests, we could see which molecules were most effective at stopping cancer cell growth.

The master switches: Why we focused on certain proteins

Our research specifically looked at three proteins inside cancer cells: CDK7, CDK9, and CDK12. Think of these proteins as master switches that help turn on the genes that cancer cells need to grow and survive. If we can find molecules that can flip these switches to the “off” position, we might be able to stop the cancer from progressing. These proteins are involved in a part of transcription called elongation, which is like making sure the instructions (RNA) are fully copied.

Navigating cancer research is like choosing the right track—each path holds different possibilities, but only one leads to a breakthrough. My work aims to guide us toward precision treatments through targeted drug discovery. Photo: Pexels.com

A step towards new treatments: What our findings could mean

Finding molecules that can block the activity of these “master switch” proteins is exciting because it could lead to new ways to treat cancer. If these molecules work in the body like they do in our lab experiments, they could become the basis for new medicines. These potential drugs might be more targeted, meaning they could attack the cancer cells specifically and cause fewer side effects in healthy parts of the body compared to some current treatments.

Keep looking, keep learning: My PhD’s contribution to cancer research

My PhD project is a part of the bigger effort to understand and fight cancer. By identifying these potential “brakes” on cancer growth, we are adding to the knowledge that scientists can use to develop better treatments in the future. There’s still a lot of work to be done to turn these findings into actual therapies for patients, but this research is an important step in that direction.

Zhijia Wang, Lab Manager, Taipale Lab. Photo: Zhijia Wang

Want to learn more about the Finnish Center of Excellence in Tumor Genetics?

Subscribe to the blog and keep up to date with the latest posts for a peek into the everyday life in cancer research.
You can also follow us on Instagram (@tumorgenetics) and Bluesky! (@coeintg.bsky.social)