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A Multistakeholder Perspective on Advancing Individualized Therapeutics

Michael Pacanowski, Julia Vitarello, Insoo Hyun, Timothy Yu, Issam Zineh

August 24, 2023


Precision medicine has evolved from the application of pharmacogenetic biomarkers to the prospective development of targeted therapies in patients with specific molecular/genetic subtypes of disease to truly “N-of-1” medicines targeted to very small numbers of patients – in some cases, a single identified patient. This latter iteration of precision medicine presents unprecedented opportunities for patients with severe, life-threatening, or life-limiting diseases. At the same time, these modalities present complex scientific, clinical, and regulatory challenges. To realize the promise of individualized medicines, a multistakeholder approach to streamlining medical diagnoses, advancing the technologies that enable development of these therapeutic modalities, and re-envisioning collaborative environments for access and evidence generation is of critical importance. Herein, we highlight some of these challenges and opportunities.


Figure 1: Evolution from precision medicine to individualized therapies. Precision approaches to patient care are shown with selected, representative examples of drug and drug target or predictive biomarker relationships (e.g., CYP2D6 metabolizer status, genetic variants in drug targets, such as CFTR, complex multigene biomarkers, such as homologous recombination repair deficiency).

“Precision medicine” is “an innovative approach to tailoring disease prevention and treatment that takes into account difference in people's genes, environments, and lifestyles.” Tailoring therapeutic interventions to certain patient characteristics has long been viewed as the goal of many precision medicine research and implementation initiatives, and the approaches to realize that goal have been constantly evolving (Figure1). Much of what we consider to be “precision medicine” in modern terms has stemmed from the use of biomarker tests to assess disease susceptibility, prognosis, or likelihood of treatment response. Early examples of therapeutic individualization through molecular/genetic testing, for example, were largely derived from observations that drug metabolism, pharmacodynamic (PD), and immunological gene variants were associated with variability in drug response phenotypes thought to be relevant to patient outcomes on the subpopulation level. Today, numerous drugs targeted to subsets of patients defined by molecular features have been successfully, prospectively codeveloped with in vitrodiagnostic tests and approved for use by health authorities (primarily for cancers, e.g., lung cancer and epidermal growth factor receptor (EGFR) mutation testing for EGFR tyrosine kinase inhibitors, ovarian cancer and BRCA1/2 testing for poly ADP ribose polymerase inhibitors).



Pacanowski, M., Vitarello, J., Hyun, I., Yu, T. W., & Issam Zineh. (2023). A Multistakeholder Perspective on Advancing Individualized Therapeutics. Clinical Pharmacology & Therapeutics, 114(5), 994–1001. https://doi.org/10.1002/cpt.3030

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