Blood vessels (shown in orange) form around tumour cells to provide nutrients and oxygen. Blocking this formation is one way to target cancer.
Each year, two million individuals are diagnosed with breast cancer, resulting in over 685,000 deaths worldwide1. Although breast cancer is the most commonly diagnosed cancer globally2, each individual’s case is unique, varying in both stage and subtype.
Scientists have been working tirelessly to research, discover and develop treatments that improve outcomes for patients. Progress has been made; however, millions of patients and their families are still waiting for effective therapies.
With over two decades in breast cancer research and patient support, Pfizer believes that further exploration of certain cell-cycle regulators, specifically cyclin-dependent kinases (CDKs), and epigenetic regulators, such as the KAT6 histone acetyltransferase, may lead to future treatment breakthroughs in breast cancer.
Unlocking the potential of next-generation breast cancer treatments
“The emergence of CDK inhibitors for the treatment of breast cancer has been pivotal in improving the standard of care for some patients and will continue to shape the next generation of treatments,” said Jeffrey Settleman, chief scientific officer, at Pfizer Oncology. As one of the first companies to harness the power of CDK inhibitors in cancer care, Pfizer has an in-depth understanding of how these molecules function within malignant cells, and the mechanisms underlying their efficacy and toxicity in patients.
Although CDK inhibitors have transformed the breast cancer treatment landscape, especially for patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer, challenges remain. Developing effective treatment options for a broader set of patients with breast cancer, including identifying molecules that can overcome drug resistance and providing patients with more effective and better-tolerated treatments, is a priority for Pfizer.
Pfizer’s next-generation breast cancer pipeline
Building on past success in breast cancer research and development, Pfizer is developing a compelling pipeline of next-generation molecules targeting cell-cycle dysregulation, each with a unique and differentiated profile. Pfizer’s CDK inhibitor early-stage pipeline leverages next-generation molecules that are designed to improve the tolerability and efficacy profiles of first-generation CDK inhibitors.
Settleman noted: “In breast cancer, certain CDK proteins become overactive, enabling cells to grow and divide uncontrollably. Pfizer’s next-generation, highly selective CDK2 and CDK4 inhibitors are designed to be more specific and potent than currently approved CDK inhibitors. By directly and concurrently targeting CDK2 and CDK4, these next-generation inhibitors may overcome potential resistance to first-generation CDK4/6 inhibitors and expand the utility of CDK inhibitors (and other cell-cycle-disrupting agents) beyond oestrogen receptor-positive (ER+) breast cancer.”
Pfizer is also developing a potential first-in-class small-molecule inhibitor of the epigenetic regulatory enzyme KAT6, which is designed to disrupt the growth of KAT6-dependent breast cancer cells. KAT6 inhibition has the potential to overcome resistance to endocrine therapy3 and CDK-inhibitor therapy4, and may achieve transformational efficacy in earlier lines of therapy when combined with CDK inhibitors and endocrine therapy.
Preclinical results for Pfizer’s novel CDK4- and CDK2-selective inhibitors will be presented at the upcoming American Association for Cancer Research (AACR) Annual Meeting in San Diego (April 5-10, 2024).
Addressing breast cancer heterogeneity with a diverse research pipeline
Breast cancer is not a singular disease. Pfizer’s goals are to develop breakthrough therapies in the metastatic setting, to help improve outcomes in earlier lines of treatment, and to provide treatment options for additional breast cancer tumour types. By applying the learnings of the past, Pfizer will continue to take bold new approaches to breast cancer research and development with the goal of successfully, effectively and safely translating scientific research into medicines that change patients’ lives.