The Future of Integration of Targeted Therapy with Genomics in Personalized Medicine

Targeted therapies guided by genomics have revolutionized medical care by providing medicine tailored to the biology of each patient, rather than one-size-fits-all treatments. As these new therapeutic paradigms are still developing in medical practice, this opinion discusses the challenges associated with implementing genomics, targeted drugs, and personalized medicine.

Ravi Dashnamoorthy Ph.D. Principal Scientist Biology, Genosco Inc

One in five people will be diagnosed with cancer in their lifetime, according to the International Agency for Research on Cancer. The number of new cancer cases will increase from 15.1 million in 2020 to 28 million by 2040. Similarly, mortality from cancer is expected to increase from 9.9 million deaths in 2020 to 16.2 million deaths in 2040. Additionally, cancer treatments impose a significant financial burden on patients, with the National Cancer Institute estimating $21 billion in financial losses in 2019. As the incidence of cancer is expected to double within the next two decades and the cost of healthcare is expected to skyrocket, it will be both an economic and a human catastrophe. Additionally, unprepared governments, a lack of significant expansion in healthcare facilities, and insufficient healthcare workers have put mankind on a path to unsurmountable tragedy. Further, the escalating incidence rate of cancer makes inpatient services at healthcare facilities extremely challenging, as current therapeutic paradigms are predominantly based on chemotherapy, radiation, surgery, etc. As a result, reducing patient foot traffic within hospitals becomes crucial in providing appropriate clinical care to patients in terminal or advanced stages of disease. Most targeted therapeutics designed to block cancer-causing molecules are developed as oral formulations, which can be taken at home under minimal medical supervision. Therefore, expanding targeted therapy use in clinical practice would reduce the strain on healthcare facilities, be cost-effective, and most importantly, deliver cancer treatments with lower toxicity and better efficacy.

For the clinical decision-making process in targeted therapy to be successful, advanced scientific knowledge and interpretation of results are necessary. A crucial part of precision medicine is genomics, which analyzes a patient's DNA or RNA to identify abnormal genetic drivers. As the human genome contains more than 20,000 genes, it becomes extremely challenging to identify which genetic abnormalities are central to cancer progression and then identify the most effective drug candidate. Currently, providers of genomic tests include algorithms that recommend potential drug candidates for each patient based on their molecular profile, leaving it up to the physician to make the decision. It is therefore necessary for physicians to research the literature or consult someone with prior experience on the same drug or patient with similar molecular profile before making their treatment plan. Although the drug manufacturer defines the matching of their targeted drug with the corresponding molecular abnormality, every patient's molecular profile is unique, and with multiple molecular abnormalities common in cancer, the entire process of adapting genomics guided precision medicine becomes overwhelming.

The field of precision medicine is still in its infancy. The development of more targeted drugs continues, with new drugs constantly entering clinical trials. Hence, we will continue to add to our compendium of successes and failures discovered during clinical trials and therapy, as it unfolds. Further, developing novel drugs and getting them approved for clinical use takes almost a decade, so establishing precision medicine will take a long time to mature and delaying the implementation for global clinical practice. Furthermore, it is important to recognize that only specialized centers can provide precision medicine care, while community oncology practices are still lagging.

As we face a race against time, advancements in precision medicine must accelerate to confront the impending disaster of an estimated 16.6 million deaths per year by 2040. To implement the clinical practice of precision medicine globally, a blueprint that estimated 16.6 million deaths per year by 2040. integrates genomics with targeted therapy principles is urgently needed. Although organizations around the world are working to establish such principles for implementing precision medicine care, there is a lack of clarity in the public about these efforts.

Personalized medicine based on genomics is gaining popularity in the field of oncology and cancer therapy but is now also widely applied to rare diseases. A major challenge for integrating genomics-based diagnostics and personalized medicine care with targeted therapies is that the biology behind complex networks of genes and pathways operating in any disease, its dynamics and progression, has not been adequately understood. The power of targeted therapy comes from blocking a single disease-associated gene/protein or pathway. However, at global levels, individual genes, proteins, and pathways rarely exist on their own, but rather interact extensively with vast biological circuits. In biological networks, parallel connections can take over and rewire away from gene-specific targeted mechanisms. Our biological network could mitigate the benefits of targeted therapy in personalized medicine by acting like the “Charlotte Web". Therefore, to overcome the "Charlotte Web" effect and reap the full benefits of target therapeutics, every disease model must outline biological circuitry and its vulnerabilities. Genomic biology assesses one gene's influence on many outcomes (genes, proteins, pathways) as opposed to one gene influencing one action (gene, protein, pathway). Without a complete understanding of disease-related biological networks and dynamics, genomic and targeted therapies would only end up as fishing expeditions.

Other imminent challenges include, establishment of clear guidelines for implementing the practice of precision

AUTHOR BIO medicine in rural communities, which is presently available for ultra-urban community only, communicating the availability of such options with patients (see Hamilton), cost factors, necessity for real time data accumulation for improving the quality of evidence based practice, ensuring data privacy, community partnership, reporting success and failures, associating with individual biology , big data analytics to implementation of treatment decision algorithms, all these requires enormous investments, and whether governmental agencies and corporates set to make profit from the implementation of such clinical advancement are willing to contribute or support these efforts to fruition remains as a big question. Investors must also recognize that as a member of this society, many will eventually experience diseases that would require personalized medicine care, thus ensuring their investments delivering the best care for themselves is utmost important, while expecting to live and enjoy their anticipated monetary returns from their so that they could live to enjoy the returns. Personalized medicine investments are currently valued at 64 billion USD but are expected to reach 166 billion USD by the end of this decade. In light of the enormous expectations already set regarding integrating genomics with targeted therapy and delivering personalized medicine, it is essential to develop the foundational knowledge of disease-associated biological networks in order to ensure profitability for both life and money in the future.

Ravi Dashnamoorthy is a Ph.D. cancer biologist who studies molecular pathways of cancer progression. As a Principal Scientist at Genosco, Billerica, USA with 25 years of academic-industry research experience in basic and translational oncology. In this column, the author represents his personal opinion, not that of any organization.