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Progress against Cancer: The Role of Basic Science

, by Douglas R. Lowy, M.D.

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The following is the second in a series of posts from senior NCI scientists and leaders on NCI’s Annual Plan and Budget Proposal for Fiscal Year 2017, which was officially submitted to the President on September 17, 2015. The proposal provides an overview of NCI’s priorities and key initiatives and the institute’s funding request for the President to consider in formulating his own Fiscal Year (FY) 2017 budget proposal.

In this second post, Acting NCI Director Doug Lowy, M.D., discusses the critical contribution of basic science in fostering progress against cancer.

Over the past two decades, we have made significant progress in diagnosing and treating cancer—progress that is reflected in the continuing declines in cancer death rates and the increasing numbers of cancer survivors. This progress is only possible because of our efforts to understand the biological mechanisms underpinning cancer, and yesterday’s announcement of the Nobel Prize in Chemistry is a clear example of this.

The DNA in our cells is continuously under the threat of damage from external and internal sources (e.g., UV radiation from the sun and free radicals generated during normal cellular metabolic activity). Nevertheless, cells have developed several mechanisms to repair damaged DNA and preserve the integrity of our genetic information.

Like a watch wrapped around a wrist, a special enzyme encircles the double helix to repair a broken strand of DNA. Without molecules that can mend such breaks, cells can malfunction, die, or become cancerous.

Credit: NIGMS / Tom Ellenberger, Washington University School of Medicine

The three scientists honored with this year’s Nobel Prize in Chemistry each elucidated a distinct DNA repair pathway. The pioneering work of these scientists and their colleagues has contributed greatly to our understanding of how normal cells function and how abnormalities in DNA repair can contribute to the development of cancer.

Abnormalities in DNA repair can be inherited or acquired during a person’s lifetime. Inheritance of a mutation that leads to inactivation of a repair pathway called DNA mismatch repair is one example of an inherited abnormality. Inherited mutations in this pathway are the cause of hereditary nonpolyposis colon cancer, one of the most prevalent cancer syndromes in humans. Acquired defects in this same pathway have been associated with a sizeable percentage of sporadic colorectal, endometrial, gastric, and ovarian cancers.

Importantly, the insights gained from the work of these three scientists are leading to the development of new cancer therapies.

For example, in December of last year, the FDA approved the drug olaparib (Lynparza™) for the treatment of advanced ovarian cancer in women who have inherited a deleterious BRCA1 or BRCA2 gene mutation. Mutations in these genes inactivate a DNA repair pathway called homologous recombination mediated repair. Olaparib inactivates a protein called PARP1, which is part of another DNA repair pathway known as base excision repair. The simultaneous inactivation of these two DNA repair mechanisms results in the accumulation of lethal amounts of DNA damage and cancer cell death.

It All Begins with Basic Research

When or where the next major advance in cancer research will occur is unknown, but it always begins with basic research—often in areas in which a direct application to medicine may not be immediately apparent, including areas such as physics, mathematics, and materials science.

As we stress in NCI’s Annual Plan and Budget Proposal for Fiscal Year 2017, NCI has traditionally made substantial investments in basic research because the institute recognizes that basic research provides the foundation and the raw materials for applied research, including the translational and clinical research arising from the outstanding work of researchers like this year’s Nobel Laureates.

Hanging Out on Google+

I welcome your comments about the role of basic research in making progress against cancer. I also encourage you to read the Annual Plan and Budget Proposal as well as the remaining blog posts in this series. And, in case you missed it live, you can watch our October 20 Google Hangout on basic science and cancer research.

NCI FY 2017 Annual Plan & Budget Proposal Blog Series

October 22: Bringing Cancer Research to the Public: NCI’s Networks and Programs

November 5: A Holistic Approach to Reducing Cancer Health Disparities

November 19: Precision Medicine Part I: Understanding Precision Medicine

December 10: Precision Medicine Part II: Clinical Trials for Adults and Children

January 13: Cancer Prevention: The Best Defense

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