When I was a sophomore in college, my mother unfortunately lost her very short battle with pancreatic cancer, an experience that changed my life forever. During that time I witnessed firsthand the devastating effects caused by the administration of toxic, non-specific treatments which ultimately failed to stop the spread of the cancer, and instead only made my mother extremely sick. Her death, at the young age of 44, profoundly influenced my feelings towards medicine and altered my career path. As a result, I became driven to discover better drugs for treating cancer, with a focus to specifically target diseased cells while leaving healthy tissues unharmed.Thankfully, my passion for developing smarter cancer drugs is shared by many others, and it has been exciting to see the progress made over the years in developing treatments that can be characterized as "personalized medicines". A commonly cited example that demonstrates the impact of personalized medicine in cancer is the successful development of the breast cancer drug, Herceptin(R), which specifically targets aggressive HER2-positive breast cancer. Importantly, before this medication was developed, women with HER2-expressing breast cancer were less responsive to standard treatments. Now, however, treatment with Herceptin in combination with chemotherapy has amazingly been shown to reduce the recurrence rate of this type of cancer by 52 percent.Building on Biomarkers: Companion DiagnosticsA biomarker is a unique trait of a disease, such as genetic marker or overexpressed protein like HER2. Developing a medicine that targets a specific biomarker can have a positive effect on patient outcome, but this approach is only one part of the therapeutic equation. To truly fulfill the promise of personalized medicine, there must also be a tool available for identifying those patients bearing that biomarker. An agent of this type is called a companion diagnostic. The outcome of this type of test should enable the right drug to be administered, to the right person, at the right time. In this manner, a companion diagnostic helps to identify those patients that may benefit from a given targeted treatment while at the same time identifying patients that will likely not benefit from therapy. Related to the example above, such a test is available to determine if a patient has HER2-positive breast cancer, and it is performed before Herceptin is prescribed.Recently, due to the benefits realized from biomarker testing, interest in developing companion diagnostics has surged. The FDA is very supportive of the development of these patient-selective tests. In fact, one companion diagnostic was approved this year and two within the same month last year to accompany Pfizer's targeted drug for lung cancer, Xalkori(R), and Roche's personalized therapeutic for melanoma, Zelboraf(R). Importantly, Roche stated that it aims to have 60 percent of its drugs in development to be accompanied by some form of a companion test, an indication that, like the FDA, the pharmaceutical industry is also embracing the continued development of companion diagnostic agents.There are many reasons for the significant interest in this space that stem from the benefits of identifying patients with companion diagnostics. For example, in the area of cancer, where development of these agents is most advanced, significant delay of tumor growth and increased survival rates have been demonstrated in patients that were preselected using a companion diagnostic. Having the ability to determine whether a patient may or may not respond to a given treatment enables the selection of the best medicine for that individual, without wasting precious time with trial and error approaches.It is precisely this advantage that allows clinical trials to be conducted in a specific patient population, which can decrease the size and related cost of these studies. Lower costs may allow drug developers to use such savings to invest in additional areas of disease research. Furthermore, smaller clinical trial size means that studies can be conducted more quickly, which could accelerate the arrival of these treatments to the market and broaden access to patients. Collectively, these conserved resources translate into savings for the entire healthcare system, which is an important benefit as rising healthcare costs are a significant issue for our nation.It is worth noting that a recent paper published in the New England Journal of Medicine showed that the genetic characteristics of a tumor, such as biomarker expression, can and often do change over time. Thus, in contrast to conventional companion diagnostics that typically utilize tissue samples obtained through biopsy (especially those performed on archived tissue), additional benefits are found with the use of companion diagnostics that are based on whole-body imaging. Results obtained from non-invasive, real-time imaging methodology, therefore, provide the most up-to-date biomarker information possible to inform treatment decision making. But, regardless of the method employed, the impact of patient selection can be substantial.A New ApproachAt Endocyte, we have seen this patient-selective approach translate into positive clinical results. The technology we're developing consists of targeted therapeutics called small molecule drug conjugates, or SMDCs. Each of these novel compounds consists of a high affinity, cell-specific targeting molecule (the ligand) that is chemically linked to a potent chemotherapy drug. This yields a highly potent, yet selective therapeutic agent; but, this approach also allows us to easily create a companion diagnostic by simply replacing the chemotherapeutic drug in the SMDC construct with an imaging agent.Vintafolide is our most advanced SMDC in development. This therapeutic binds to the folate receptor, which is a confirmed biomarker expressed on many human cancers, including ovarian, lung, breast and colon. Vintafolide's companion diagnostic imaging agent (etarfolatide) is designed to identify cancer patients that have high levels of the folate receptor expression, which is the exact population of patients expected to respond to this drug.In a previous clinical trial in patients with platinum-resistant ovarian cancer, women identified as "FR-positive" by etarfolatide and then subsequently treated with vintafolide had significantly delayed tumor growth. Based on these unprecedented results, especially in a patient population that fails to adequately respond to any therapy, both etarfolatide and vintafolide are being considered for conditional approval in Europe. This could mean that patients would have access to these agents much sooner than expected. Overall, this exciting opportunity would never have been possible if our companion diagnostic agent was not used to select the right patient population to treat with vintafolide in our clinical trials.A Promising FutureBecause of the numerous benefits companion diagnostics hold for patients, physicians, drug developers and our healthcare system, their continued development and use will only increase in the future. Regulatory agencies worldwide are also embracing this approach, and they continue to encourage drug developers to pursue this path for the treatment of all types of diseases. As the number of companion diagnostics in development continues to grow, we are moving closer each day to truly fulfilling the promise of personalized medicine. Follow Scientific American on Twitter @SciAm and @SciamBlogs.Visit ScientificAmerican.com for the latest in science, health and technology news. 2012 ScientificAmerican.com. All rights reserved.

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Advancing the Promise of Personalized Medicine: Companion Diagnostics