By Aparna Krishnan
The idea of tailoring a disease treatment to your unique genetic, environmental, and lifestyle profile is very promising. This personalized approach to medicine would likely lessen patients’ side effects and increase their chances of survival. In the newly established field of precision medicine, this concept is already becoming a reality.
The impetus of the precision medicine movement was the Human Genome Project. The Human Genome Project, completed in 2003, was the first complete mapping of all the genes in the human genome. Researchers located and identified nearly 20,500 genes in the human body to study how they are organized and potentially mutated in different diseases. This first effort to sequence a human genome cost a $100 million but since then, the cost has decreased significantly into the $1,000 range.
Following this large-scale effort to jumpstart precision medicine, the next huge advancement in the field was President Barack Obama’s $215 million Precision Medicine Initiative (PMI) in 2015—a research effort to move away from a one-size-fits-all approach to treating disease, particularly in cancer detection and treatment. Today, this initiative continues with the National Institutes of Health’s All of Us research program and our very own JP Sulzberger Genome Center here at Columbia. Andrea Califano, director of Columbia’s Genome Center, states that “the [Human] Genome Project has significantly improved our ability to learn how tumor cells work at the molecular level—the more we learn their inner workings, the better we’re able to develop effective therapies.” But how exactly does this molecular analysis of tumors give way to more accurate, personalized therapeutics? Let’s look at an example:
Suppose there is a large cohort of about 500 breast cancer patients. Traditionally, in a one-size-fits-all approach, the drug which showed the most promising results in the clinical trial would become FDA-approved and then, eventually administered to the entire cohort. However, breast cancer, like all cancers and diseases, are very heterogeneous (meaning they contain many molecular and genetic variations) and consist of several intra-tumor subtypes. Because different patients’ tumors have unique molecular profiles that respond to the same therapeutic very differently, it is unlikely that a single drug can treat all breast cancer patients equally and as effectively. In fact, some patients could even react negatively to that drug if it doesn’t match their profile, leading to severe side effects such as cognitive changes, hair loss, bruising, and bleeding.
The alternative to this one-size-fits-all method is precision medicine. Precision medicine involves Next Generation Sequencing (NGS), an extremely rapid technique for sequencing an individual’s DNA or RNA. Using NGS, researchers can identify potential genetic mutations or molecular biomarkers contributing to the growth of a patient’s tumor and divide patients with that cancer into smaller subgroups based on their common molecular abnormalities. By breaking down a larger cohort into smaller subtypes, each patient can receive a treatment tailored to their subgroup’s defining molecular profile. This concept has already come into fruition for breast cancer—PARP inhibitors appear most effective for patients with a BRCA mutation, while CDK4/6 drug inhibitors are promising therapeutic candidates for patients with the HR+ subtype. The list of recent therapeutic discoveries in precision medicine is endless and goes beyond just breast cancer.
Providing a sense of this rapid expansion of the field, a 2019 published report from the Personalized Medicine Coalition stated that personalized therapies have provided a possible cure for hepatitis C, restored vision loss from congenital blindness, and improved the overall survival and progression-free survival rates for patients with breast, lung, and colorectal cancer. In 2018 alone, there was a record of 25 personalized medicines approved, accounting for 42 percent of all 2018 drug approvals. This growing percentage demonstrates the FDA’s ongoing commitment to accelerating precision medicine in the pharmaceutical market. The field has made huge strides in the way patients are profiled, diagnosed, and treated for diseases and will continue to revolutionize medicine moving forward.
The promises of this new era of precision medicine are essential for both researchers and the general public to recognize. The field itself is constantly evolving and heavily layered with intricate details that may even push people away from the field’s daunting technologies and advanced science. Nevertheless, having a conceptual understanding of precision medicine and staying up-to-date on the field’s advances will undoubtedly prepare us all for its growing influence on our future healthcare system.