4 Rays of Hope for 'Precision' Cancer Therapies

Posted: 12/16/2014 12:34 pm EST Updated: 12/16/2014 4:59 pm EST

Trends in cancer research promise to change treatment prospects, perhaps not for those who are seriously ill today, but surely for many of those who will follow.

In 1971, the nation declared a war on cancer, implying that cancer was one disease for which a single cure could be found if we only did enough research. Since then, and despite billions of dollars invested in cancer research, nearly 600,000 people will still die in 2014 from cancers that out-ran the pace of scientific discovery. So the critical question is: "What has cancer research done to give individual cancer patients more hope?"
The answer is, "A lot."

Through most of the intervening years, our understanding of the basic science of cancer has led to potential breakthroughs. William C. Phelps, Ph.D. and director of the American Cancer Society's Preclinical and Translational Cancer Research Program, explains that, "We know that cancer is actually 100-200 different diseases that can affect 60 different organs. For years, researchers have challenged the premise of cancer being a single disease with a singular cure, broadening the portfolio of treatments beyond traditional surgical, radiation, and chemotherapy options. Yet new therapies' full potential couldn't be realized until we invented sophisticated tools for matching available treatments to individual patients and their cancers."

Now four advances in basic cellular science and information technology are fueling long-awaited progress:

Genomics

Proteomics

Immunomics

Big Data

As each matures, their combined promise could be stunning.

Genomics

Traditional cancer treatments have focused on the individual body parts where the cancer appears and on using powerful chemicals (chemotherapies) to kill cancer cells. Unfortunately many of those drugs also damage healthy cells, causing undesirableside effects (like nausea, blistering, pain, and heart issues). If treatments could targetjust the cancer cells, patients would have better survival prospects and a higher quality of life.

One source of progress stems from genomics, the study of how our genes predispose our bodies toward disease. By analyzing the molecular structure of an individual's cancer, scientists are now able to identify specific genetic mutations (abnormalities) that may cause disease. Mutations may vary from one cancer cell to another in the same patient, and the same genetic mutation may cause cancers in different parts of the body. For example, mutations in the BRCA1 gene (best known for its predictive role in breast cancer) have also been implicated in some fraction of ovarian, prostate, and pancreatic cancers.

Dr. Phelps explains that even individuals with the same genetic mutation may experience the same type of cancer and the same treatment in different ways because "each person metabolizes the same drug differently and breaks it down very differently." As a result, the drug that's most appropriate and its optimum dosage can vary by person. Identifying specific genes and processes that affect the growth, spread, and/or death of cancer cells, or that cause resistance to a particular therapy, can lead toward "precision" (or personalized) treatments that target only the cancer cells and are most likely to work for the individual, based on his genetic profile.

Proteomics
Proteomics (a second type of specialized research) is the study of the proteins expressed by a patient's genes to control how the body functions. Scientists are now studying how proteins are structured and expressed, how their concentrations change, and how they interact. These studies are beginning to reveal how some proteins' presence and concentrations correlate with the presence and progression of certain cancers.

Dr. Robert J. Mayer, medical oncologist and professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, says that further progress may depend on the ability to discern "predictive biomarkers that lead us to distinguish whether one given form of therapy is more or less likely to be beneficial in a given person."

The challenge of identifying such protein biomarkers was compared by Katleen Verleysen, CEO of Pronata, as "spotting a bee from space."

Scientists are also studying the body's protein and enzyme "switches" that turn on or off cancer's growth or response to therapies to understand why some cancers develop drug resistance. For example, the New York Times reported on Dec. 6 on successful Phase I drug trials by Bristol-Myers Squibb and by Merck that block action by a protein that blocks the immune system from attacking certain solid tumors and blood cancers.

Immunomics
A third research focus studies how the immune system works and pursues therapies that will trigger it against cancer. The Cancer Research Institute callsimmunotherapies the "most promising new cancer treatment approach since the development of the first chemotherapies in the late 1940s."

Immunotherapies are targeted to turn on or off the flow of certain proteins that are instrumental in the growth or death of cancer cells. Scientists are now exploring the presence of particular biological molecules (biomarkers) with certain types of cancer cells to learn how to activate the body's immune responses.

Big Data

The implications of the term "big data," once a mystery to laymen, are growing clearer for the cancer world. "Big data" in the cancer world refers to powerful analytical tools for extracting meaningful patterns from millions of available data bits to learn what patient characteristics and treatment regimens produce the best outcomes.

Electronic medical records, genomics, proteomics, and immunomics together generate a volume of data that are forcing an informatics revolution as learning initiatives (both public and private) begin to correlate clinical and genomic data and look toward someday incorporating proteomic and immunological data.

Light at the End of the Tunnel?

When they arrive, precision therapies may guide each individual's cancer treatments for improved survival and quality of life. Yet today we can generate more information than can be integrated and analyzed.

Further progress depends on expanding informatics capacity and standardizing data formats to integrate massive volumes of clinical, genomic, proteomic, and immunomic data from diverse institutions. Years of effort and billions more research dollars are needed to accelerate personalized medicine's promise, but potential future benefits fuel enormous hope to reduce suffering and deaths from cancer.