Next generation sequencing and tumor mutation profiling: are we ready for routine use in the oncology clinic?

Debu Tripathy,Kimberly Blackwell,Mark Robson,Kathleen Harnden

doi:10.1186/s12916-014-0140-3

Abstract

Next generation sequencing (NGS) coupled with sophisticated bioinformatics tools yields an unprecedented amount of information regarding tumor genetics, with the potential to reveal insights into tumor behavior. NGS and other multiplex genomic assays are rapidly spilling from the laboratory into the clinic through numerous commercial and academic entities. This raises the important question as to whether we are ready to use these data in clinical decision-making. While genetic lesions are clearly targeted by a new generation of biological cancer therapies, and certain regulatory approvals are actually coupled to single gene assays, we still do not know if the vast information on other genomic alterations is worth the added cost, or even worse, the inappropriate and unproven assignment of patients to treatment with an unapproved drug carrying potentially serious side effects. On the other hand, the trend toward a precision medicine pathway is clearly accelerating, and clinical trials validating pathway-driven personalized cancer therapeutics will be necessary in both the community and academic settings. Lower cost and wider availability of NGS now raises a debate over the merit of routine tumor genome-wide analysis.

Highlights

Are we ready in the clinic? Debu Tripathy (Figure 1)As with most new technologies and treatments, molecular diagnostics are entering the oncology arena in phases
The concept of ‘precision medicine’, defined as therapy that is personalized to unique disease and host characteristics, has taken huge leaps in the cancer field with the advent of generation sequencing (NGS) [1,2]
This is evidenced by the successful targeting of BRAF mutation (V600E)-associated melanoma with BRAF and downstream MEK inhibitors, but the lack of efficacy in BRAF-mutated colorectal cancer, perhaps due to more genomic alterations and resultant bypass pathways [7,8]

Summary

Introduction

Are we ready in the clinic? Debu Tripathy (Figure 1)As with most new technologies and treatments, molecular diagnostics are entering the oncology arena in phases. NGS has no proven benefit, the theoretical advantage is that it may identify a clinical trial or even drug approved for a different cancer type that MIGHT be helpful. A recent trial for patients with advanced breast cancer that performed array comparative genomic hybridization for copy number variation and gene sequencing (AKT and PI3KCA only) and assigned them to a panel of drugs that were known or presumed to address the genetic lesions.

Results

Conclusion