October 21, 2013 - Seven of 10 medical decisions are made using information from diagnostic tests or laboratory services. These decisions range from checking blood sugar levels to selecting a targeted cancer medicine. Right now, no other field influences as many medical situations as laboratory testing. And it will only become more integral to therapy as we create even more targeted treatments.
You can’t have one without the other
Targeted medicine has two main components – the medicine itself and the diagnostic that can identify which patients to treat with that medicine. Each is equally important in making sure that a patient receives the treatment that is tailored to the particular type of disease.
Every new medicine, targeted or not, is backed by a robust set of data from clinical trials. The data collected is used by regulatory authorities to vet the medicine and will ultimately support its approval. Accordingly, a diagnostic, which guides the use of a medicine, should be supported by robust data as well.
Inaccurate or unreliable testing could cause patients to be overlooked for potentially useful therapies or to be exposed to unfavorable side effects without any chance of benefit. As we move into an age of more personalized treatments, we must apply the same importance to the validity of the diagnostic as we do to the medicine.
Out of the lab and into the clinic
Tailoring cancer care is not an easy task, but we are advancing in this field. We have a better understanding of the inner workings of tumors. We can measure what genes are mutated and which proteins are overabundant on the cell surface. But measurement is only a piece of the puzzle. Understanding the advantages and limits of each test is important to determine its usefulness.
Not all diagnostics are created equal, nor are they designed to be. They have to be based on the type of genetic alteration in the target of the drug and the most effective way in which to detect it. For example, a technique called Fluorescent In Situ Hybridization, FISH for short, is designed to measure if there are multiple copies of a particular gene. A technique called Immunohistochemistry, or IHC, can reveal if there is an overabundance, or overexpression, of a protein on a cell surface, which correlates to some cancer abnormalities. However, IHC cannot reveal if that protein has a mutation that causes overactive signaling. Both of these tests are used to detect overexpression of the HER2 oncogene, a marker for a type of HER2-positive breast cancer. Yet another technique is based on the ability to amplify segments of cancer-causing genes by polymerase chain reaction, or PCR, to identify mutations that render normal cell signals overactive leading to an increase in cell proliferation, or cell survival. For example, the b-RAF oncogene in malignant melanomas is based on the detection of a key mutation, V600E, in b-RAF.
All of these tests are used to determine if a person is an appropriate candidate for a specifically targeted drug. Now that we are able to collect this information, the challenge is how to make it useful to doctors and patients. How do we prioritize testing for biomarkers, or indicators of disease? Which biomarkers can actually inform treatment decisions? Which types of tests should we use and is there data to support it?
The changing landscape of diagnostic and laboratory testing means that doctors will need to evolve as well. Pathologists and laboratory professionals will become more active members of the treatment team. Pathologists will have a greater knowledge of which tests are valid and which should play a role in the ultimate care of the patient. As molecular testing increases, the role of the diagnostician to assist doctors and patients in mapping out more targeted choices will grow as well.
Charting the course for the future
The evolution of diagnostics is not static. New technologies, such as next generation sequencing, are being developed to ask even more diagnostic questions of a patient’s cancer, resulting in more comprehensive and efficient diagnoses. Indeed, key mutations in tumors are now detectable in the blood of cancer patients, enabling monitoring of therapeutic intervention over time. We have already seen the impact of this in other diseases. For example, people with HIV are now tested on a regular basis to monitor the amount of the virus in their blood. This test, combined with current medicines, enables doctors to stay ahead of relapses - by keeping the amount of the virus depressed or even undetectable.
In cancer, scientific insights into tumor progression and resistance, along with new, targeted medicines and diagnostic technologies, are converging to get ahead of resistance and relapse at the molecular level before detection at the clinical level. For example, if cancer cells or the DNA from those cells are detected in the blood before tumor progression is identified on a PET or CT scan, then the possibility to stay ahead of disease relapse is much greater. The advent of molecular targeted therapy coupled with diagnostics tests is one way we are trying to tailor the treatment of cancer. As we develop ever more medicines, our approach to diagnostics has to keep pace. We must ensure that our use of tests is backed by robust data and that there is an engaged and diverse treatment team who can help doctors and patients navigate the increasing landscape of choices.