The Johns Hopkins University School of Medicine

Valsamo Anagnostou

Precision medicine is getting the right treatment to the right patient at the right time, however identifying the most effective cancer treatment can often be a complex and timely process. While the number of approved therapies constantly increases, the efficacy of each therapy varies from patient to patient and this is in-part attributed to the unique genetic make-up of each cancer. To this end, understanding each cancer’s molecular profile is a key first step to identify tailored treatments and ensure that patients receive potentially life-saving therapies. The field of precision oncology is evolving rapidly because of advances in molecular testing, that includes laboratory techniques to identify changes in the genetic make-up (or DNA) of the cancer, or in the molecules that carry and translate the instructions held in the DNA (we call this RNA) or in the levels of proteins in the cancer cells. Next generation sequencing is a type of molecular testing that can pinpoint the genetic information in the patient’s DNA and highlight changes in the DNA sequence or structure, that we call mutations. A number of treatments capitalize on the fact that cancers harbor mutations in key genes and the emergence of targeted or molecularly-tailored therapies has led to significant improvements in clinical outcomes and has prolonged survival for individuals with cancer.

Nevertheless, the widespread use of molecular testing and next generation sequencing does not come without challenges. The interpretation of molecular testing of blood or tumor tissue can be complex and for some patients the key question of how we make informed decisions to treat patients based on the genetic make-up of their cancer remains unanswered. As co-leader of the Johns Hopkins Molecular Tumor Board and the Lung Cancer Precision Medicine Center of Excellence at the Sidney Kimmel Cancer Center at Johns Hopkins, I am working with multi-disciplinary teams of experts in medical oncology, molecular pathology, genetics and data science focusing on addressing precisely this question: How do we match the molecular profile of a patient’s tumor with the best available therapy? Molecular Tumor Boards are expert-opinion-based precision oncology initiatives that have been shown to improve outcomes by matching genomic profiling of tumors with available therapies as standard of care or in the context of a clinical trial. As an example, the Johns Hopkins Molecular Tumor Board that I am leading together with Dr. Jessica Tao, is a state-of-the-art multidisciplinary molecular tumor board that reviews tumor and liquid biopsy molecular profiling reports, carefully interprets the genomic findings and provides personalized recommendations tailored to the genetic footprint of each individual’s cancer. We are particularly interested in molecular profiling of blood, also known as liquid biopsies, that represent an emerging minimally invasive approach to capture the genetic make-up of cancer in the bloodstream and use liquid biopsies in the context of clinical trials to get the most comprehensive information about how cancer changes over time and tailor therapy (NCT05585684 and NCT04093167 are two representative examples).

Maximizing the efficacy and accessibility of molecular tumor boards represents an urgent need in precision oncology. Oncologists in academic institutions and most importantly in the community typically face a large volume of molecular data that is frequently intuitively processed to support high-stakes decisions. To address these critical challenges, we are working within the Johns Hopkins Molecular Tumor Board, in collaboration with health informatics and data science experts as well as liaising with community hospitals to develop a decision support platform that augments the value of precision medicine. We are designing a decision-support system to guide clinical decision-making by tailoring results of next generation sequencing to evidence-based ranked therapies in an automated, scalable and generalizable manner. We envision that this end-to-end precision oncology analytical platform will enable clinical decision making and patient selection for genotype-driven clinical trials. We are particularly interested in the practical implementation of our work in health care settings outside our local academic environment and as such and we have partnered with community oncology and pathology teams within the Johns Hopkins Community Research Network.

As a cancer researcher, dedicated to benchto-bedside translation I am enthusiastic about the advancements in molecular testing and their clinical implementation, that have allowed for delivery of precision oncology to our patients with cancer. Our research aims to further propel the implementation of precision oncology and ultimately increase patient enrollment in genotype-matched clinical trials and impact clinical outcomes for our patients with cancer.