In recent decades, advances in breast cancer treatment have helped to improve health outcomes for many patients, but scientists remain vigilant in their quest to further reduce both the incidence and impact of the disease. Breast cancer is one of the most common cancers in women, with about one in eight women in the United States alone diagnosed during their lifetimes.i Metastatic breast cancer, a more advanced and invasive form of the disease, remains a particularly critical area of unmet need and a key focus for Pfizer’s research and development teams. Now, a discovery is bringing them one step closer to a potential breakthrough in first-line care.

What Is Metastatic Breast Cancer?

Metastatic breast cancer (MBC) occurs when cancer cells spread beyond the breast to other organs in the body. It can affect men, but it is more frequently diagnosed in women. Although significant progress has been made in both screening and treatment, MBC remains a leading cause of cancer-related deaths among women globally and is currently incurable.i,ii

Taking Up the Charge: Helping to Address the Unmet Need

Chemotherapy, immunotherapy, surgical intervention, radiation, and combination approaches have all played – and continue to play – an important role in the ongoing battle against cancer, but there is no “one size fits all” model when it comes to this highly complex and devastating disease. There is still a significant need for new and innovative treatment options, and Pfizer scientists have been at the forefront of many of these exciting discoveries.

One notable advancement in breast cancer treatment over the past decade has been the development of cyclin-dependent kinase (CDK) inhibitors. These drugs work by blocking the activity of specific enzymes—such as CDK4 and CDK6—that play a key role in driving cancer cell growth. They offer a more targeted and tolerable approach compared to traditional chemotherapy, which does not distinguish between rapidly dividing cancer cells and healthy cells.

Though CDK4/6 inhibitors have helped revolutionize treatment for the most common form of metastatic breast cancer, scientists did not stop there.

“As science has developed, we’ve been able to target even more precisely the drivers of disease and ideally differentiate them from potential drivers of side effects,” said Britton Boras, a translational modeling and simulation specialist at Pfizer.

With a series of key discoveries and new technologies, Britton and a team of Pfizer scientists believed they could design an even more selective inhibitor which could be administered over longer periods, potentially leading to greater tolerability and improved efficacy.

Innovating for the Future of Cancer Treatment

CDK4 and CDK6 enzymes are remarkably similar in their structure, making it incredibly difficult – previously thought impossible – to develop an inhibitor that targets only one. Researchers believe that CDK6 predominately affects blood cells while CDK4 plays a key role in breast cancer cell cycle division, making it the preferred target for this new approach.

By leveraging advanced understanding of protein structures, cutting-edge technology, and sophisticated chemical techniques, they discovered subtle differences in the enzymes’ binding pockets. This breakthrough has allowed them to design a therapeutic candidate, now in a Phase 3 clinical trial, that specifically inhibits CDK4, which offers the potential for more complete and continuous target coverage and may improve tolerability, subject to clinical success and regulatory approval.

And their work is still not done. Pfizer is also exploring potential combinations of CDK4 with other novel mechanisms of action.

“It’s not yet known whether CDK4 inhibitors can be applied in other types of cancer, but our team is exploring the possibility,” explains Jennifer Lafontaine, head of oncology medicinal chemistry at Pfizer.  “We love to see the data come in and imagine the number of patients our work could impact. It’s incredibly motivating.”

Learn more about Pfizer’s work on and commitment to breast cancer.

 

i Key Statistics for Breast Cancer. American Cancer Society. Updated January 22, 2025. Accessed March 17, 2025. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html
ii Treatment of Stage IV (Metastatic) Breast Cancer. Updated September 28, 2025. Accessed November 13, 2025. https://www.cancer.org/cancer/types/breast-cancer/treatment/treatment-of-breast-cancer-by-stage/treatment-of-stage-iv-advanced-breast-cancer.html