SAN FRANCISCO-Matthew Ellis, MD, BChir, PhD, Director of the Lester and Sue Smith Breast Center and Professor of Medicine and Cellular and Molecular Biology at Baylor College of Medicine, was awarded the 2015 Gianni Bonadonna Breast Cancer Award and Lecture here at the 2015 Breast Cancer Symposium. The award recognizes Ellis' research on the clinical relevance of activating mutations in HER2 and the deployment of patient-derived xenografts for the pharmacological annotation of breast cancer genomes.
Ellis played a key role in developing a Genome Atlas and Therapeutic Road Map for estrogen receptor-positive breast cancer. He is also co-leader for The Cancer Genome Atlas Breast Project and co-principal investigator for the Clinical Proteomic Tumor Analysis Consortium, which has the aim of translating TCGA genomic discoveries into protein-based biomarkers with clinical utility.
Ellis' lecture walked through some of the seminal findings by him and his colleagues that have guided his work and led him to investigate the new theory that maybe genomic testing to guide therapy in breast cancer is of more limited value than has been thought.
"With genomics, it's not just measuring enough of what you need to know in most cases," he said in an interview after the session. "We're good at identifying poor-prognosis patients using genomic profiling or grade-we have lots of surrogates for poor prognosis. But we still don't know exactly how to rescue those patients' poor prognosis with a very targeted approach. We haven't made enough progress, and we need to develop new approaches to actually measure the biochemistry that we need to drug."
Proteomics
Those new approaches may come in the form of proteomics, he explained. "The role of the mutations are to disrupt the biochemistry either via an accelerating mutation, like a HER2 mutation, or by stopping the negative receptors, like tumor suppressors.
"The idea of the proteomic profile is where we can measure all the biochemistry, so we get the integrated effect of these mutations and get to see exactly how which biochemistry has become active-and in particular, which kinase has become active so we can drug that kinase. So, you're drugging to kinase activity, not to the mutation."
And that's what the Clinical Proteomic Tumor Analysis Consortium (funded by the National Cancer Institute) is all about, Ellis explained. "There are some new technologies on the horizon-mainly focusing on the proteomic approaches where we can better understand what are the biochemical events that are unleashed by the mutations. And you're trying to drug that biochemistry.
"So this next approach is going to integrate proteomics, where you're measuring not just the genes, but also proteins to build a better map of the treatment approach."
The Bonadonna Legacy
The award, which has been given annually since 2007, was named in honor of cancer research pioneer Gianni Bonadonna and recognizes an active clinical and/or translational researcher with a distinguished record of accomplishments in advancing the field of breast cancer and who has exceptional mentoring abilities. The presentation of this year's award included an extra tribute to Bonadonna, who died in September at age 81 (OT 10/25/15 issue). In a video shown here at the meeting, several of the award's past recipients praised Bonadonna's contributions as scientist, clinician, mentor, and humanitarian.
Ellis gave his own tribute to the award's namesake by sharing a thought Bonadonna had passed down to the 2011 recipient, Luca Gianni, MD, of San Raffaele Cancer Center in Milan (which L. Gianni had shared with Ellis via email): "Gianni expressed to me in a book his regret of having realized too late and too little the key aspect of empathy and human attention to the patient."
Ellis added: "In our drive to achieve scientific advances and put patients on trial, we still have to remember that each patient is struggling and each patient requires our empathy and our attention. Sometimes I say to the patients, 'if at the end you feel better as a result of my consultation today, I'll have partially achieved my job.'"