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Samuel Aparicio, BM, BCh, PhD, FRCPath FRSC
Nan & Lorraine Robertson Chair in Breast Cancer Research
Canada Research Chair in Molecular Oncology
Distinguished Scientist and Head, Department of Molecular Oncology,
BC Cancer, a part of the Provincial Health Services Authority
Professor, Department of Pathology & Laboratory Medicine
Fellow, Royal Society of Canada, Life Science Division
University of British Columbia
Research Area: Decoding the genomic makeup of triple-negative breast cancer and developing new strategies to personalize therapy for patients.
Impact: While many patients who have triple-negative breast cancer (TNBC) respond to drugs that damage DNA, such as platinum-based drugs, new treatments are urgently needed to treat those who do not. One major challenge is that TNBC is a group of diseases that are not fully understood, complicating the development of targeted therapies. Dr. Aparicio's work decoding the genome sequences of TNBC is now revealing vulnerabilities that could be used to design effective targeted therapies. His team has observed at least four distinct patterns in the DNA structure of TNBC tumors that could predict response to drugs that directly target DNA. They are determining which of these DNA markers is associated with drug resistance or may be a biomarker for risk of metastasis. He hopes that the results of these studies will lead to more personlized treatment approaches and improve outcomes for patients with aggressive TNBC.
Progress Thus Far: They have characterized the mechanism of action of CX-5461, a new DNA targeting agent, which will inform which patients may benefit from its use. Clinical trials to test CX-5461 are currently underway. In results recently published in the journal Nature, Dr. Aparicio and his team showed that TNBC tumor cells that develop resistance to platinum therapy undergo dynamic changes in the pattern of DNA structures. Moreover, they were able to define distinct stages during these changes where resistance could be reversed.
What's next: Dr. Aparicio will build on his findings and continue to determine which specific DNA pattern within TNBC tumors increases the susceptibility to various agents including CX-5461. He hopes this work will lead to future clinical trials to look for the presence of DNA characteristics that may identify patients at risk of metastasis. His novel approach leverages a convergence of science and new technologies—such as single cell analysis and translational medicine—bringing expertise from diverse fields to solve a difficult problem, how to recognize and defeat TNBC in the clinic.
Full Research Summary
Research area: Decoding the genomic makeup of triple-negative breast cancer (TNBC) to improve approaches to treatment.
Impact: Dr. Aparicio has observed at least four distinct patterns in the DNA structure of TNBC tumors—patterns that could predict response to drugs that directly target DNA. They are determining which of these patterns is associated with drug resistance or may predict tendency to metastasize. They are also examining the mechanism of action of a new drug and hopes these studies will lead to better treatment approaches and outcomes for patients with the aggressive TNBC subtype.
Current investigation: He and his team are using genome sequencing to determine specific DNA pattern within TNBC tumors that increase the susceptibility to CX-5461 treatment.
What he’s learned so far: Dr. Aparicio has discovered at least four distinct patterns of shuffling of the structure of chromosomes in TNBC tumors—patterns that may be predictive of sensitivity to drugs that directly target DNA. They have characterized the mechanism of action of CX-5461, a new genome targeting agent that is currently in clinical trials, to understand which TNBC patients may benefit from treatment.
What’s next: Dr. Aparicio’s discovery of distinct subclasses of TNBC is a crucial advancement in improving treatment approaches for his aggressive type of breast cancer. He and his team will continue to assess how the specific patterns in chromosomal structure shuffling in different TNBC subtypes may predict treatment resistance or metastasis. Their approach is a convergence of science and new technologies—such as single cell analysis and translational medicine —and brings expertise from diverse fields to solve a difficult problem, how to recognize and defeat TNBC in the clinic.
Dr. Samuel Aparicio (BM, BCh, PhD, FRCPath) is the Nan & Lorraine Robertson Chair in Breast Cancer Research, holds the Canada Research Chair in Molecular Oncology, and is the recipient of the 2014 Aubrey J Tingle Prize. He is also Head of the BCCA’s Department of Breast and Molecular Oncology, and a Professor in the Department of Pathology and Laboratory Medicine at UBC.HE graduated in medicine from Cambridge undertook clinical training in Oxford, subsequently in internal medicine and pathology. After doctoral work with Sydney Brenner in Cambridge he held a Wellcome Trust Career Development Fellowship at the Wellcome/CRUK Developmental Biology Institute. From 2000-2005 he was a senior investigator in the Department of Oncology, Cambridge. He was a co-leader of the international consortium that sequenced the genome of the pufferfish Fugu rubripes in 2002 and a visiting professor at the IMCB, Singapore.
Dr. Aparicio’s research program encompasses the fields of cancer genomics, laboratory genetic models, high throughput screens, small molecule chemical probes and translational breast cancer research. His most recent work on the molecular taxonomy of breast cancer led to identification of new genes that could change the way breast cancer is diagnosed and form the basis of next-generation treatments. This discovery was preceded by another breakthrough in decoding the genetic makeup of the most-deadly form of breast cancer, known as triple negative subtype. Dr. Aparicio is also working to develop quantitative measures of clonal fitness in patients, including methods for single cell genome sequencing and PDX models of human cancer. He collaborates widely with other groups, with current projects including the genomic and biochemical analysis of lymphoma, ovarian cancer, and several rare pediatric cancers. He was a co-founder of Paradigm Therapeutics (now, Takeda Cambridge) and currently Contextual Genomics Ltd.
As a physician-scientist, the key philosophy of Dr. Aparicio’s program has been to provide a strong multidisciplinary environment for training of highly qualified personnel (HQP). His former trainees (career total 90) have gone on to success in academia: 1 institute director, 3 as PIs and others in medicine or in senior positions in industry or postgraduate education. All of his graduate students have been successful in securing national (CIHR, NSERC) or provincial (Michael Smith Foundation, CBCF BC/Yukon) competitive salary support and two of the four postdoctoral fellows are supported by independent peer reviewed salary awards from international (Australia), national (CBCF) and provincial (MSFHR) funding bodies.
Dr. Aparicio has published 172 papers in genomics and genetics of disease with >35,000 citations (H-index 77, i10 index 151). He has published in such high impact journals as: New England Journal of Medicine, Nature, Cell, Science, Nature Medicine, Nature Genetics, Nature Methods, Cell Stem Cell and Cell Metabolism.
BCRF Investigator Since
The Estée Lauder Companies' Canada Award