Inaugural Issue
Spring 2013 

Michelle M. Le Beau, PhD, is the Director of the University of Chicago Comprehensive Cancer Center, and President of the Association of American Cancer Institutes

Commentary Overview

*  Clinical oncology is transitioning from treatment based on a tumor's anatomic site to treatment guided by a tumor's molecular characteristics

*  Many challenges impede implementation of comprehensive molecular diagnostics at cancer centers

*  "Precision Oncology" will be the focus of Dr. Le Beau's AACI Presidential Initiative
About AACI Commentary

As part of AACI's efforts to promote the work of its member centers to both general audiences and the cancer research community, AACI has launched AACI Commentary, a quarterly editorial series. Written by cancer center leaders, each issue will focus on a major issue of common interest to the nation's cancer centers.

Precision Oncology Implementation at the
Nation's Cancer Centers


Historically, the clinical management of patients with cancer has been based on the anatomic site and tumor histology. In the past few decades, the identification of pathogenic mutations within oncogenes or tumor suppressor genes that confer sensitivity to targeted therapies has resulted in a paradigm shift to one where the molecular characteristics of a tumor play a critical role in guiding the selection of therapy. Numerous challenges impede the implementation of comprehensive molecular diagnostics within cancer centers, including the acquisition of appropriate tissues, development of mutation panels, selection of technology platforms and regulatory reimbursement policies. A new AACI initiative, briefly described below, seeks to identify such challenges, and to offer guidelines and best practices for the molecular diagnostics of cancer.


Introduction and Scope of the Problem

Clinical oncology is transitioning from a treatment paradigm based on the anatomic site of tumor origin to one in which the molecular characteristics of the tumor guide selection. Moreover, targeted cancer therapy requires the development and implementation of companion diagnostic approaches that identify those patients who are most likely to respond to a particular therapy. Several contemporary examples, such as EGFR mutations that predict sensitivity to gefitinib or erlotinib, and KRAS mutations that confer resistance to tyrosine-kinase inhibitors, provide a firm foundation for using specific mutations as predictors of response to selective agents. However, the future landscape of cancer therapy is likely to be far more complex.

In addition to the challenges of selecting the most relevant abnormalities, numerous technical and practical issues exist, including approaches to specimen collection and specimen size (e.g., core needle biopsies), quality, inherent tumor heterogeneity, the admixture of non-malignant and malignant cells, and the requirement for robust assay performance in formalin-fixed paraffin-embedded tissues. The deregulation of a core group of common signaling pathways is believed to drive the pathogenesis of human tumors, supporting the application of a broad genotyping platform to all tumors, rather than restricting the analysis to focused mutational panels for specific cancer types.

In contrast to existing tests assaying a single or limited number of genes, or gene products, the development of new technologies, such as protein and gene arrays, and high-throughput sequencing enables screening of the entire genome, proteome, transcriptome, and metabolome for new biomarkers that may better reflect the complex molecular aberrations within a single tumor that can be exploited for the development of rationally designed therapies.

Diagnostic technologies and platforms are evolving rapidly, and the selection of optimal platforms, and the development of the necessary informatics infrastructure, test standardization and reporting, as well as the integration with the clinical research enterprise, are formidable challenges for cancer centers. Another barrier to advancing personalized medicine is inadequate reimbursement rates for molecular testing through private insurance or Medicare, which does not support the development of molecular diagnostics, or provide incentive for optimization.

AACI Presidential Initiative

Given the number of challenges that must be addressed to advance molecular pathology, this is an opportune time to empower cancer centers by sharing best practices for molecular diagnostics of cancer. To that end, precision oncology will be the focus of my AACI presidency. With the help of AACI Vice-President/President-elect Dr. George Weiner and AACI staff, we are in the early stages of identifying a selective range of precision oncology topics of vital interest to AACI members as they weave the evolving science into the fabric of their research and patient care. Once these areas of interest are determined, we will assemble an expert panel of cancer center colleagues to provide input on best practices in implementing precision oncology at the nation's cancer centers.

Potential topics under consideration for this initiative include:

Precision Medicine Tumor Board
Composition: Genetic counselor, psycho-oncologist, ethicists, oncologists, molecular pathologists, pharmacogenomics expertise
Role and responsibilities of the board
Relationship to cancer risk clinic and genetic counseling

Consent forms
Tissue collection (e.g., fresh frozen tissue, FFPE, biopsies vs. core biopsies)
Informatics infrastructure
Start-up Costs
Biobanking: Best practices, evolving regulatory and College of American Pathologists guidelines

Responsibility of hospital versus cancer center
Who should be tested? Broad-scale testing vs. specific subgroups?
Use of outside genomic data
Incorporating molecular diagnostics into the design of clinical trials

Communicating results to patients, oncologists and care providers

Representing 95 of the nation's premier academic and free-standing cancer research centers, the Association of American Cancer Institutes is dedicated to promoting leading research institutions' efforts to eradicate cancer through a comprehensive and multidisciplinary program of cancer research, treatment, patient care, prevention, education and community outreach.