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Pfizer Builds on Nobel Prize-Winning Research to Fight Cancer

Pioneering Nobel Prize research of the cell cycle

In 2001, three scientists, Leland H. Hartwell, Tim Hunt and Sir Paul M. Nurse, won the Nobel Prize – an honor beyond measure – for their outstanding contributions to the study of the cell cycle. Prior to that time, scientists understood the basics of how cells grow and divide, but they did not have a detailed understanding of the process. In other words, they did not know which specific proteins and signaling pathways within the cell controlled the cell cycle. 

Understanding the cell cycle

The cell cycle is a fundamental process of life that governs how a cell grows and divides. The process consists of four phases: the G1 Phase where the cell grows, S Phase where the cell copies its genetic information (i.e. DNA), G2 Phase where the cell continues to grow and prepares to divide, and M Phase where the cell divides into two identical cells.1 The average human body is made up of approximately 37 trillion cells, which all started from a single cell – the fertilized egg. For a human body to grow, the cell cycle is essential to produce more cells which form tissues and organs. Importantly, the cell cycle needs to be turned off, when appropriate, so cells do not continue to divide uncontrollably.  The human body could not exist without the cell cycle.

The Nobel Laureates make a breakthrough discovery

Hartwell, Hunt and Nurse discovered that the cell cycle is regulated by cyclin dependent kinases (CDKs). Professor Anders Zetterberg, who gave the Nobel Prize presentation speech and was a member of the Nobel Committee at the Karolinska Institute, stated that a “CDK is comparable to a ‘molecular engine’ that drives the cell through the cell cycle by altering the structure and function of other proteins in the cell.”2

The cell cycle lies at the heart of cancer

Ultimately, their scientific discovery would have a great impact on cancer research.  A key characteristic of a cancer cell is an uncontrolled cell cycle, resulting in unrestrained growth and division. CDKs are key to driving the cell cycle.  This laid the groundwork for Pfizer scientists to identify the first molecule that could specifically inhibit CDK4 and CDK6 (collectively called CDK 4/6) – which have been found to play a role in cancer by restraining the uncontrolled growth and division of a cancer cell.3

Leading the way in therapy development

Building on more than 20 years of research, scientists at Pfizer Oncology discovered that inhibiting the activity of CDK 4/6 during the initial (G1) phase of the cell cycle could interrupt the growth and reproduction of  cancer cells.4,5,6 This has led to treatment advances for patients with a certain metastatic, or stage 4, cancer, and scientists at Pfizer Oncology are now examining the role of CDK 4/6 inhibitors in earlier stages of cancer.

“We are committed to building on our legacy of innovative science and leadership in this new class of cancer therapy,” said Mace Rothenberg, MD, Chief Development Officer, Oncology, Pfizer Global Product Development, “We continue to explore the potential of CDK 4/6 inhibitors for their role in putting the brakes on cancer cell division.” 
 

1Weinberg RA. pRb and Control of the Cell Cycle Clock. In: The Biology of Cancer. 2nd ed. New York, NY: Garland Science, Taylor & Francis Group, LLC; 2014.
2Award Ceremony Speech. Presentation Speech by Professor Anders Zetterberg of the Nobel Committee at Karolinska Institutet, December 10, 2001. https://www.nobelprize.org/nobel_prizes/medicine/laureates/2001/presentation-speech.html
3Nobel Media AB 2014. The Nobel Prize in Physiology or Medicine for 2001 - Press Release. Last Accessed April 24, 2017. Available at: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2001/press.html
4Sotillo E, Graiia X. Escape from Cellular Quiescence. In: Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY: Humana Press; 2010.
5Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 2006;24(11):1770-1783.
6Finn RS, Dering J, Conklin D, et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11