Home > Precision Cancer Medicine

What is Precision Cancer Medicine?
  Most medical treatments are designed for the "average patient" as a "one-size-fits-all-approach," which may be successful for some patients but not for others. Precision medicine, sometimes known as "personalized medicine" is an innovative approach to tailoring disease prevention and treatment that takes into account differences in people's genes, environments, and lifestyles. The goal of precision medicine is to target the right treatments to the right patients at the right time.
  Advances in precision medicine have already led to powerful new discoveries and several new FDA-approved treatments that are tailored to specific characteristics of individuals, such as a person's genetic makeup, or the genetic profile of an individual's tumor. Patients with a variety of cancers routinely undergo molecular testing as part of patient care, enabling physicians to select treatments that improve chances of survival and reduce exposure to adverse effects.
  To further these advances, the 21st Century Cures Act of 2016 encourages the FDA to develop new regulatory approaches for the oversight of genomic technologies as part of the Precision Medicine Initiative. The Precision Medicine Initiative seeks to identify genetically-based drivers of disease in order to develop new, more effective treatments.

Next Generation Sequencing (NGS) Tests
 Precision care will only be as good as the tests that guide diagnosis and treatment. Next Generation Sequencing (NGS) tests are capable of rapidly identifying or 'sequencing' large sections of a person's genome and are important advances in the clinical applications of precision medicine. Patients, physicians and researchers can use these tests to find genetic variants that help them diagnose, treat, and understand more about human disease.
How does Precision Cancer Medicine work?
  The purpose of precision cancer medicine is not to categorize or classify cancers solely by site of origin, but to define the genomic alterations that are driving that cancer. Even if an alteration occurs in a given cancer type only 1 percent of the time, and you can provide an effective treatment option for those specific patients, it’s incredibly enabling and powerful.

Why is Precision Cancer Medicine Important?
  Each person is unique, and so is his or her cancer. Precision medicine is based on the belief that cancer treatment can be tailored to the genetic makeup of each patient’s cancer cells, and to his or her physiology and medical history. We have a long way to go before this precise, genetics-based cancer treatment can help every person with cancer, but this approach is proving to be a powerful way of attacking cancer.
  By studying the cancers of thousands of patients, researchers are developing a deep understanding of the genomic and biologic factors that drive cancer growth, and are using this knowledge to develop better therapies. We have already identified many genetic mutations in cancer cells that are potential targets for therapy, and are working on identifying still more. And we are working closely with pharmaceutical companies to develop and test potential drugs that strike directly at these mutations.
  With precision cancer medicine, researchers and clinicians work side by side. “Systematically studying all patients allows us to identify the specific genetic weaknesses of their tumors.
  Our goal is to provide the most effective therapy by combining targeted agents with conventional treatments. We will also able to better anticipate complications that could be caused by a specific gene aberration.
  This approach was good news for the special education teacher who was diagnosed in 2011 with stage 4 lung cancer that had spread to her lymph nodes and produced a lesion on her hip. A DNA test indicated that her cancer contained an EGFR (epidermal growth factor receptor) mutation, a molecular subtype of cancer that is common in non-smokers. Fortunately, researchers at DF/BWCC had discovered a drug that specifically targets the EGFR mutation.
  The patient participated in a clinical trial for the now-FDA approved drug Tarceva, but after 18 months her tumors began growing again. This time, DF/BWCC researchers identified a new, previously unknown resistance mutation in EFGR, T790M that was blocking the effectiveness of Tarceva, and provided a second combination of experimental agents. Although effective for a short time, the new targeted therapy stopped the tumor growth for only a few months.
  A third clinical trial, where she is being treated with a new EGFR-inhibitor referred to as AZD9291, also developed at DF/BWCC, is proving to be effective. Her tumors are shrinking and the side effects are minimal. Now retired, she continues fighting her disease with minimal side effects three years after her once-fatal diagnosis.
  Precision cancer medicine is accelerating our ability to bring basic research to our patients. It also reverses the flow of information, and completes the circle by bringing what we learn at the bedside right back to the laboratory to keep the process of discovery going.

The Future of Precision Cancer Medicine
  As scientific research and computational analysis deepen our understanding of cell biology, we are moving toward the promise of precision cancer medicine. Using next-generation DNA sequencing to thoroughly scan the cancer genome, and large, data-intensive research projects like Profile to better understand the disposition and behavior of cancer cells.

 

Breast cancer
 Not all patients respond equally to cancer therapeutic compounds. Recent advances in high-throughput genomic, transcriptomic, and proteomic technologies with the ever-increasing understanding of the molecular mechanisms of cancers permit uncovering genes that harbor personal variations in clinical outcomes or drug responses. Personalized medicine has revolutionized the healthcare paradigm by integrating personal genetic information, improving the drug treatment efficacy, shifting the practice of medicine, and creating opportunities to introduce new business and healthcare economic models.
  The traditional standard "one-dose-fits-all" approach to drug development and clinical therapy has been ineffective, as it incurs all risks of subsequent drug toxicities and treatment failures. With the great variability across diseases, 38% to 75% of patients fail to respond to a treatment. The average response rate of a cancer drug is the lowest at 25%.
  Aadverse drug reactions as a consequence of treatment are more of a problem. Among drugs approved in the U.S., 16% have shown adverse drug reactions. A frequently cited meta-analysis revealed that 6.7% of all hospitalized patients are associated with adverse drug reactions in the U.S. and that the number of deaths exceeds 100,000 cases annually.A study conducted in a major hospital identified 2,227 cases of adverse drug effects among hospitalized patients and reported that 50% of these cases are likely to be related to genetic factors.
  Personalized medicine is the ability to segment heterogeneous subsets of patients whose response to a therapeutic intervention within each subset is homogeneous . Under this new healthcare paradigm, physicians can make optimal choices to maximize the likelihood of effective treatment and simultaneously avoid the risks of adverse drug reactions; scientists can improve the drug discovery process, and pharmaceutical companies can manufacture medical devices to forecast patient prognosis, facilitating early disease detection.
  The ultimate goal of personalized medicine is to furnish the proper treatment to the right person at the right time. The potential impact of personalized medicine is contingent upon a systematic discovery of a novel biomarker from genome-wide candidates that account for variations across individuals. This review begins with an overview of personalized medicine and illustrates the most encountered statistical approaches for uncovering biomarkers utilized in the recent literature.

Definition of personalized medicine: individualized treatment vs. Treatment for a sub-patient group
  Personalized medicine has been defined in many ways. According to the U.S. National Institutes of Health (NIH), personalized medicine is "an emerging practice of medicine that uses an individual's genetic profile to guide decisions made in regard to the prevention, diagnosis, and treatment of disease". The U.S. Food and Drug Administration defined personalized medicine as "the best medical outcomes by choosing treatments that work well with a person's genomic profile or with certain characteristics in the person's blood proteins or cell surface proteins" . The President's Council of Advisors on Science and Technology (PCAST) described personalized medicine as "tailoring of medical treatment to the individual characteristics of each patient".
  It is important to recognize that personalized medicine does not literally mean individuality. The idea of personalized medicine has often been exaggerated, as suggested in a headline in Newsweek (June 10, 2005) "Medicine Tailored Just for You." In fact, a new treatment regimen is assessed on a group of carefully selected patients but not individuals. As such, PCAST reports that personalized medicine is "the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment". If a new treatment works effectively on a sub-patient group, a preventive intervention can then be furnished to those who will benefit, avoiding adverse drug effects and sparing expense for those who will not.

Biomarkers: prognostic vs. Predictive
  A biomarker is a reliable and accurate measurement that indicates a normal biological process, a pathogenic process, or a pharmacological response to a therapeutic intervention. With this broad and general definition, biomarkers include physiological measurements such as lung function, blood pressure or electroencephalography, molecular (DNA, protein, metabolite) or cellular measures from biofluids (blood, plasma, serum, and urine), molecular, cellular or histopathological measures from solid tissue samples, and measurements from magnetic resonance imaging or computed tomography images.