Track and attack! A needle in the Hay Stack:

By Dr Gargi, Professor, Amity Institute of Biotechnology, Amity University Gurugram

Introduction: Precision or personalized medicine is a novel healthcare approach that uses a patient’s genomic, proteomic and lifestyle-based information to create tailored healthcare choices for diagnosis, treatment and prevention of diseases. This is beyond the ‘one size fits all’ approach and targets unique disease characteristics, resulting in fewer side effects and better outcomes. It is a paradigm shift from the conventional, reactive disease control approach to a proactive, patient-specific disease treatment and prevention.

The Human Genome project which unfolded in 2003 gave scientists better insight into the role of various genes and their involvement in diseases. The evolution of genomics era makes precision medicine possible. The genomic and protein composition of an individual allows us to understand his/her short- and long-term disease risks at a molecular level, which can be used to predict disease risks and provide suitably tailored remedies. Precision medicine allows us to identify that one gene or mutation that is responsible for causing (or can cause) disease in patients. This particular gene/protein/RNA can be used as a biomarker for that disease. Specific biomarkers can be developed for early detection of disease, disease monitoring, and development of therapeutics. Developing therapeutics based on an individual’s molecular profile can maximize treatment efficacy and minimize adverse effects to surrounding tissues and organs.

One key application of precision medicine is in the treatment of cancer. Problem in diseases such as cancer is heterogeneity, i.e. two tumours may look the same, but have completely different molecular profiles leading to different clinical outcomes. This variability in cancer is a major obstacle in diagnosis and treatment. This difference is further compounded by differences in genetics, metabolism, lifestyle, of a patient which can influence patient response to disease and treatment. Precision medicine addresses this issue by targeting specific biomarkers, checking genetic profile of the individual using Next-Generation Sequencing, and providing a customized treatment or prevention plan based on these results.

For example, aberrant tyrosine kinase activity is central to the pathogenesis of human cancers. However, before the year 2000, tyrosine kinase-based therapies were not available. Targeted therapy using selective tyrosine kinase inhibitors (TKIs) has transformed the management and treatment of various cancers, resulting in a therapeutic breakthrough. Imatinib was one of the first cancer therapies to show the potential for such targeted action. Imatinib or Gleevec is an oral targeted therapy that inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. This drug was invented in 1990s by Nicholas Lyndon who worked for Ciba-Geigy (now Novartis), and was used to treat chronic myelocytic leukemia (CML) for the first time by Brian Druker, an oncologist at the Dana-Farber Institute. Subsequently Dr. Charles Sawyers supervised its use in several clinical trials where it showed tremendous potential for treatment of CML and got fast track approval from FDA for treatment of patients. For their discovery, Lyndon, Druker, and the other colleagues were awarded the Lasker-DeBakey Clinical Medical Research Award in 2009 and recognised their contribution for “converting a fatal cancer into a manageable condition”.

The story of the famous Hollywood actress Angelina Jolie is well known and exemplifies how biomarkers can impact life choices. She underwent preventive surgery, a double mastectomy, as she carries the BRCA1 gene mutation. The mutation significantly increases the risk of breast and ovarian cancer. Angelina’s mother, grandmother, and aunt were afflicted by breast cancer. The doctors calculated her risk of breast cancer to be 87%, and therefore she chose to have her breasts removed to reduce that risk to under 5% as a proactive measure. 

The cost of personalised therapy is currently quite high, but likely to decrease through a combination of technological advancements, and increased collaboration among healthcare stakeholders.  Also, though the initial costs are high, this approach saves money in the long run by avoiding ineffective treatments and hospitalizations. 

Use of precision medicine is rapidly expanding beyond cancer, to target conditions such as genetic disorders, respiratory diseases, cardiovascular diseases and infections. With the help of precision medicine, we would soon be able to match the right treatment with the right patient at the right time, based on their unique genetic makeup, environment, and lifestyle, instead of bombarding them with generic treatment based merely on symptoms and preconceived notions. This is likely to revolutionise the field of medicine like never before as diagnosis, treatment and preventive measures would be accurate instead of presumptive, based on precise knowledge about an individual’s genetic makeup and predisposition. 

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