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Patrice Hugo, Ph.D. | February 05, 2016

Fighting cancer takes precision

On February 4, we commemorated World Cancer Day, a day when researchers, physicians, patients and other interested groups acknowledge all the hard work being done to fight this global disease. This year in the healthcare community, we took another step closer to improving healthcare worldwide. 

For years, oncology researchers dealt endless frustration over failed trials of promising drugs that inevitably worked well but only in very small groups of patients. These results were crushing, but they also led researchers to follow new paths that ultimately led them to the incredible results we are seeing today in precision medicine. By identifying the unique characteristics and genetic variants in those specific patient populations who responded well to those drugs, they have been able to develop targeted therapies that have shown tremendous success rates for specific types of cancers.

One of many early examples is the treatment of women suffering a type of breast cancer in which they over-express a protein called HER2 (human epidermal growth factor receptor 2), which makes breast cells grow and divide in an uncontrolled way. HER2-positive cancers, which make up about 25 percent all breast cancers, tend to grow faster and are more likely to spread and come back compared to HER2-negative breast cancers. However, thanks to advances in precision medicine, researchers were able to generate advanced diagnostic tools to measure HER2 protein expression or HER2 gene amplification in breast cancer cells, and develop targeted treatments, including Herceptin®, to treat a selected population of patients predicted to respond better to this type of therapy. In fact, it has been shown that Herceptin® improves 10-year overall survival rates to 84 percent among this patient population.

This is just one example of how precision medicine has impacted oncology research. Today there are more than 20 cancer drugs that require specific characterization of the tumor to identify the best therapeutic options, including gastric cancer, chronic myeloid leukemia, colorectal cancer (CRC), breast cancer, non-small cell lung cancer (NCSLC), and others.1 Pharmacogenomics also uses patients’ genetic background to identify the exact dose of chemotherapeutic drug based on the individual ability of liver enzyme to metabolize the drug and to determine the genetic background of a specific gene to predict drug toxicity.1  For example, HIV patients with a gene variation called HLA-B*5701 are at a much higher risk of experience severe side effects from abacavir, a common and productive HIV medication. A simple blood screening can ensure these patients don’t receive the drug, thus helping to avoid safety issues with the treatment.

Another area of exciting innovations involve the use of biomarkers to track the physio-pathological state of the patient via liquid biopsies. Instead of requiring a tumor biopsy, liquid biopsies use blood for example samples to count the number of circulating tumor cells (CTCs) present in the patient, and to characterize the genetic material of such cells to monitor cancer progression and identify optimal therapeutic options.  In related research, the US Food and Drug Administration (FDA) has approved the measurement of circulating tumor cells as a way to monitor the recurrence of breast cancer, CRC and prostate cancer, making it easier and less invasive for physicians to track cancer progress.   Furthermore, many studies are under way to determine the clinical utility of detecting genetic material (e.g. DNA) in the blood or urine (refer to as circulating free DNA –cfDNA- or circulating tumor DNA –ctDNA-) originating from solid primary or metastatic tumors as a surrogate biomarker in cancer patients and potentially as a mean to characterize the tumor cells to determine the best therapeutic options.  Together, there is building evidence that liquid biopsies (CTC or cfDNA) could offer an alternative faster and cheaper approach for physicians to screen and monitor patients, and potentially detect changes in their cancer sooner and through a less invasive way than with a tissue sample. 

Immunotherapy: training cells to fight cancer
The development of a new effective class of drugs targeting the immune system is another small revolution currently taking place in cancer treatment. The concept of immuno-modulators have been explored and tested in the clinics for years but only in the recent years that a new set of immune targets have shown dramatic impact on patient’s survival. Merck, Bristol-Myers Squibb (BMS) and many other companies have developed biological drugs, such as therapeutic antibodies that can be used to block proteins expressed by the tumor cells to inhibit the patient immune response to kill the tumor. Such drugs are referred to as immune checkpoint inhibitors.2 Spectacular clinical results have been achieved with melanoma and NCSLC and now there are more than 250 ongoing clinical trials to tests different immuno-oncology drugs in various cancer indications.

We still have a long way to go with all of this research, and we must continue to deal with the ongoing challenge of recruiting the right patients to these trials, and finding new ways to bring drugs to market quicker and more cost effectively. That includes working more closely with physicians to pre-screen potential trial applicants, implementing digital tools to improve the way we gather and analyze data, and collaborating through industry partnerships to harness more agile development processes. The accomplishments we’ve achieved in recent years prove that we have the talent and tools to beat cancer, as long as we continue to invest our best minds and resources into the fight. We also have to acknowledge the extraordinary contributions from cancer patients and their family in supporting clinical trials leading to the development of innovative and superior diagnostic and therapeutic options.

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