Building a personalized medicine infrastructure at a major cancer center

Abstract

Our understanding of cancer biology is rapidly increasing, as is the availability and affordability of high throughput technologies for comprehensive molecular characterization of tumors and the individual's own genetic makeup. Thus, the time is right to implement personalized molecular medicine for all patients with cancer. Personalized approaches span the full cancer care spectrum from risk stratification to prevention, screening, therapy, and survivorship programs. Several molecular therapeutics have entered clinical trials creating a huge opportunity to couple genomic markers with this emerging drug tool kit. The number of patients managed in major cancer centers creates a challenge to the implementation of genomic technologies required to successfully deliver on the promise of personalized cancer care. This requires a major investment in infrastructure to facilitate rapid deployment of multiplex, cost-effective, and tissue-sparing assays relevant across multiple tumor lineages in the Clinical Laboratory Improvement Amendments (CLIA) environment. Efforts must be made to ensure that assays are accessible to patients most likely to be enrolled onto molecular-marker-driven trials and that the tests are billable and payable, which will make them accessible to a wide range of patients. As the number of patients and aberrations increase, it will become critical to provide decision support for genomic medicine. Institutional commitment is needed to optimize accessibility and quality of research biopsies and to facilitate novel personalized cancer therapy trials. This article will focus on the challenges and opportunities that accompany the building of infrastructure for personalized cancer therapy.

Fig 1.

The personalized cancer care continuum.

Fig 2.

Biomarker discovery based on unusual responders on targeted therapy. In-depth molecular characterization of tumors from patients with objective response to single-agent targeted therapy or targeted combinations, patients with unexpected rapid progression, and patients with mixed response can give critical insights into intertumoral heterogeneity (represented by different color clones within the tumors), and mechanisms of intrinsic sensitivity and resistance. Characterization of tumors that relapse after initial response may give unique insights into mechanisms of acquired resistance.

Fig 3.

Leveraging information from unusual responders for biomarker discovery.

Fig 4.

Exploring the clinical utility of comprehensive genomic testing. After patient informed consent, tumor and normal DNA is extracted in the Clinical Laboratory Improvement Amendments (CLIA) environment. After targeted somatic mutation testing in the CLIA environment, more extended testing is performed in a research environment. Test results are shared with the treating oncologists, and CLIA validation of research findings is pursued if any clinically relevant research findings are found. Therapeutic decisions are based only on CLIA test results.

Fig 5.

Sequential genomic analysis. Genomic testing may be performed in a sequential manner in the clinical setting, with Clinical Laboratory Improvement Amendments (CLIA) –targeted genomic testing followed by more extensive genomic testing until actionable aberrations are identified.