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LRF Grantee Identifies Genetic Marker Affecting Outcomes for DLBCL Patients

A study authored by a LRF Career Development Award winner identified a genetic marker that may indicate diffuse large B-cell lymphoma (DLBCL) patients who will not respond well to standard treatments. Kai Fu, MD, PhD, of the University of Nebraska Medical Center was corresponding author for the study, published in the December 20, 2013 issue of the Journal of Clinical Oncology. Dr. Fu received an LRF Clinical Research Career Development Award (CDA) in 2009 which provided salary support for a portion of the time spent on this research.

The STAT3 transcription factor is not always activated in DLBCL patients, but Dr. Fu's previous research demonstrated that STAT3 activation is a common feature in patients with the activated B-cell subtype (ABC-DLBCL). For this study, Dr. Fu and his collaborators examined STAT3 expression in 185 patients with DLBCL who were treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), as well as data from a previously published group of 222 DLBCL patients. Of the 407 total patents, 37% had STAT3 activation. These patients, particularly those who belonged to the ABC subtype group correlated with poor overall survival rates and event free survival (the length of time after treatment free of cancer symptoms or progression). This correlation suggests that DLBCL patients who test positive for STAT3 activation are at greater risk to have their cancer relapse or fail to respond when treated with R-CHOP, a discovery which not only indicates a need for alternative treatments for this subgroup, but suggests that researchers investigating new therapies in DLBCL should pay particular attention to the results for patients with STAT3 activation to determine if their therapies will address that need.

Dr. Fu's collaborators included a number of LRF Scientific Advisory Board (SAB) members, including Julie Vose, MD, also of the University of Nebraska, Elaine Jaffe,MD and Louis Staudt MD, PhD, both of the National Cancer Institute, Randy Gascoyne, MD of BC Cancer Agency, and Wing (John) Chan, MD, Dr. Fu's mentor at Nebraska during his CDA project, now at City of Hope. The researchers hope that their findings will lead to a new line of treatments for STAT3 positive DLBCL patients. "The next step in the research is to use a specific STAT3 inhibitor to see if it helps the R-CHOP chemotherapy regimen work more efficiently and improve patient survival rates by identifying patients who are at higher risk" Dr. Fu says.

The abstract of the article is available online at the Journal of Clinical Oncology website. Full text of the article will be made available to the public in December 2014.

March 2014