SAN FRANCISCO, CA USA (UroToday.com) - In this session Dr. Eliezer M. Van Allen discussed the potential role for next generation sequencing (NGS) technologies in developing an individualized approach to the treatment of bladder cancer.
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Dr. Van Allen started with a summary of the NGS technologies. NGS profiling identifies all mutations present within the genetic material that is tested, which can range in scope from a predefined set of exons (targeted sequencing) to the entire exome or whole genome sequencing. Targeted and exome sequencing are now ready for use in the clinical setting.
Currently therapeutic decision making is fairly limited in bladder cancer. The goal of the insertion of NGS profiling in this decision-making process, Dr. Van Allen elaborated, was to identify mutations specific to an individual patient’s cancer which could lead to the use of novel targeted therapeutics. NGS profiling could also help to identify patients more or less likely to respond to standard therapies.
Recent studies have demonstrated multiple potential targets in bladder cancer, including FGFR, RAF, MET, mTOR, PI3K and AKT1. Dr. Van Allen discussed his work with NGS profiling of over 500 exomes in diverse bladder tumor types and reported the presence of a “long tail” of mutated clinically relevant cancer genes – namely a large number of genes mutated at a low frequency. This fact emphasizes the need for individualized treatment strategies given the significant heterogeneity present within bladder cancer. Dr. Van Allen further explained that through the use of an algorithm developed in his lab called “PHIAL”, clinical and biologic relevance of any identified pathway alterations could be ranked, and thus targeted therapies most likely to be efficacious could be identified.
Dr. Van Allen finally discussed potential future applications of NGS in bladder cancer. The identification of mutations related to the development of clinical resistance through profiling of tumor tissue, before and after development of resistance, could help to drive the identification of new therapeutic targets. Ultimately the hope would be that NGS profiling would continue to identify new targets within an individual patient’s cancer that would allow for utilization of new targeted therapies that could potentially keep a patient’s cancer at bay indefinitely.
Highlights of a presentation by Eliezer M. Van Allen, MD at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
Dana-Farber Cancer Institute, Boston, MA USA