David Malkin

Senior Staff Oncologist, Division of Haematology/Oncology
Co-Lead, Precision Child Health
Co-Director, Cancer Genetics Program

Director, Cancer Genetics Program
Senior Scientist, Genetics & Genome Biology

Other Positions

Co-Chair, Board of Scientific Counselors, National Cancer Institute (US)
Co-Director, Canadian Pediatric Cancer Consortium 
Director, Precision Oncology for Young People (PROFYLE)

Dr. Malkin is Professor of Paediatrics and Medical Biophysics in the Faculty of Medicine, University of Toronto. He holds the CIBC Children’s Foundation Chair in Child Health Research, is a Staff Oncologist in the Division of Hematology/Oncology, Director of the Cancer Genetics program, and a Senior Scientist in the Genetics & Genome Biology Program at The Hospital for Sick Children (SickKids) in Toronto. Dr. Malkin co-leads the SickKids Precision Child Health initiative. He co-directs the SickKids Cancer Sequencing (KiCS) program which integrates next generation sequencing (NGS) into clinical care of children with cancer, and Director of the pan-Canadian PRecision Oncology For Young peopLE (PROFYLE) initiative which is establishing a pipeline to incorporate NGS into novel clinical trials for children and young adults with hard-to-cure cancers across Canada, and co-leads the Canadian Pediatric Cancer Consortium (ACCESS).

Dr. Malkin’s research focuses on genetic mechanisms of childhood cancer susceptibility, particularly in the context of TP53 and Li-Fraumeni syndrome. Recently, his work has addressed the application of genomics to clinical surveillance and treatment approaches for children and adults at genetic ‘high risk’ for cancer. Dr. Malkin’s research is funded by a variety of agencies and he has published over 325 peer-reviewed manuscripts. Dr. Malkin holds grants (PI/co-PI) totalling ~$61M including precision oncology/ predisposition/childhood cancer consortia projects (~$42M) and primary research studies in early prediction and cancer interception in genetically at-risk populations (~$19). He has trained 175 students (49 summer students, 9 MD Research Fellows, 51 MSc/PhD thesis committee students, 40 graduate students and 26 PDFs). He has received numerous awards recognizing his clinical, research and mentorship work, most recently being elected a Fellow of the Royal Society of Canada and the American Association for Cancer Research, and receiving a King Charles III Coronation Medal ‘for his contributions to Canada’. Dr Malkin’s extensive collaboration networks and internationally recognized leadership in the fields of pediatric cancer genetics and clinical pediatric oncology have facilitated and enhanced the focus of his academic program: to develop a fundamental understanding of the molecular basis of Li-Fraumeni syndrome specifically and cancer predisposition/precision oncology in general, and apply this knowledge to transform the clinical management of children with cancer.

Research

Dr. Malkin has dedicated his research and clinical oncology career to the study of and care for children with cancer in the context of familial cancer syndromes. As a post-doc, he discovered that germline mutations of the TP53 tumor suppressor gene cause >80% of LFS, and are linked to an increased risk of second tumors and early onset osteosarcoma, even in the absence of a family history of cancer. Since 1992, his research group has refined the molecular definitions of LFS, characterized genetic events that modify the phenotypic effects of an underlying germline TP53 mutation, and elucidated a model of tumor initiation/progression in LFS in which a constitutional (or possibly early somatic) TP53 mutation favours the accumulation of epigenetic/genetic events that facilitate accelerated telomere attrition, catastrophic/punctuated genomic events (eg. chromothripsis), and subsequent somatic cell transformation. Translating his work into direct clinical relevance, we developed a surveillance protocol, the so-called “Toronto Protocol” that takes advantage of innovative imaging techniques such as rapid whole-body MRI. This protocol has been adopted and validated worldwide and demonstrates feasibility of early tumor detection with substantial survival benefit. Dr. Malkin has recently enhanced this approach by developing and validating multi-omic ctDNA biomarkers together with ML/AI-guided platforms to enhance prediction of age-of-onset and tumor type in LFS. As Director of the Cancer Genetics Program at SickKids, he has amassed over 5000 samples from children with a wide variety of cancer susceptibility disorders, sarcomas and other cancers. To complement the molecular work, Dr. Malkin has established and published from rich collaborations exploring the ethical and psychosocial impact of cancer predisposition and genetic/genome research in pediatrics. In the last 6 years, he has expanded his breadth of cancer genetics research to developing and leading both local (SickKids Cancer Sequencing (KiCS) and national (Precision Oncology for Young People (PROFYLE)) large-scale peer-reviewed efforts in pediatric precision oncology, with over 800 and 1500 patient tumor/paired normal samples sequenced to date in the respective programs (WGS, WES, RNAseq, 800+ gene targeted panel) – identifying actionable targets in over 50% leading to modifications in clinical management. These efforts bring together a vast array of disciplines from genetics/genomics/ bioethics/ medical and pediatric oncology/functional biology/proteomics and clinical trials expertise.

Education and experience

• 1989-1992: Post-Doctoral Fellow, Molecular Genetics, Harvard University, Boston, USA
• 1988: Fellow (Pediatrics), Royal College of Physicians and Surgeons of Canada
• 1980-1984: MD, University of Toronto, Toronto, Canada

Achievements

• 2024: Niehaus, Southworth, Weissenbach Award (Memorial Sloan Kettering Cancer Centre)
• 2024: King Charles III Coronation Medal (Government of Canada)
• 2024: Alyssa Lyons Award of Valour – Israel Cancer Research Fund
• 2024: Elected Fellow - Academy of the American Association for Cancer Research (AACR)
• 2023: Queen’s Platinum Jubilee Community Service Award (Government of Canada)
• 2022: Elected Fellow of the Royal Society of Canada
• 2022: O. Harold Warwick Prize, Canadian Cancer Society
• 2022: AACR-St. Baldrick’s Foundation Award for Outstanding Achievement in Pediatric Cancer Research
• 2020: Global Pioneer Award, Li-Fraumeni Syndrome Association
• 2017: Denis Daneman Faculty Development Award, Department of Pediatrics, University of Toronto
• 2015: Henry Friesen Award, Canadian Society for Clinical Research/Royal College of Physicians and Surgeons of Canada
• 2013: Transformational Leadership Award, Canadian Cancer Society
• 2011: Senior Fellow (Elected), Massey College, University of Toronto
• 2006: Physician Researcher Award for Scientific Accomplishment, Department of Pediatrics, The Hospital for Sick Children, University of Toronto
• 1997-2003: Dr. Harold E. Johns Award, Outstanding Research Scientist. Canadian Cancer Society

1. Malkin D, Strong LCS, Li FP, Fraumeni JF, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, Friend SH. Germline p53 mutations in a familial syndrome of breast cancer, sarcomas and other neoplasms.  Science 1990: 250: pp 1233-1238.

2. Villani A, Shore A, Wasserman JD, Stephens D, Kim RH, Druker H, Gallinger B, Naumer A, Kohlman W, Novokmet A, Tabori U, Tijerin M, Greer M-LC, Finlay JF, Schiffman JD, Malkin D*. Biochemical and imaging surveillance in TP53 mutation carriers with Li-Fraumeni syndrome: 11 year followup of a prospective observational study. Lancet Oncology Sep;17(9):1295-305, 2016.

3. Kratz CP, Freycon C, Maxwell KN, Nichols KE, Schiffman JD, Evans DG, Achatz MI, Savage SA, Weitzel JN, Garber JE, Hainaut P, Malkin D*. Analysis of the Li-Fraumeni Spectrum Based on an International TP53 Variant Dataset. JAMA Oncology 7(12): 1800-1805, 2021.

4. Light N, Layeghifard M, Attery A, Subasri V, Zatzman M, Anderson ND, Hatkar R, Blay S, Chen D, Novokmet A, Fuligni F, Tran J, de Borja R, Agarwal H, Waldman L, Abegglen LM, Albertson D, Finlay JL, Hansford JR, Behjati S, Villani A, Gerstung M, Alexandrov LB, Somers GR, Schiffman JD, Rotter V, Malkin D*, Shlien A*. Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis. Nat Commun 2023 Jan 5;14(1):77. doi: 10.1038/s41467-022-35727-y.

5. Villani A, Davidson S, Kanwar N, Lo WW, Li Y, Cohen-Gogo S, Fuligni F, Edward LM, Light N, Layeghifard M, Harripaul R, Waldman L, Gallinger B, Comitani F, Brunga L, Hayes R, Anderson ND, Ramani AK, Yuki KE, Blay S, Johnstone B, Inglese C, Hammad R, Goudie C, Shuen A, Wasserman JD, Venier RE, Eliou M, Lorenti M, Ryan CA, Braga M, Gloven-Brown M, Han J, Montero M, Spatare F, Whitlock JA, Scherer SW, Chun K, Somerville MJ, Hawkins C, Abdelhaleem M, Ramaswamy V, Somers GR, Kyriakopoulou L, Hitzler J, Shago M, Morgenstern DA, Tabori U, Meyn S, Irwin MS, Malkin D*, Shlien A*. The clinical utility of integrative genomics in childhood cancer extends beyond targetable mutations. Nat Cancer. 2023 Feb;4(2):203-221.

6. Wong D, Luo P, Subasri V, Oldfield L, Gong H, Fischer NW, Laverty B, Kim RH, Malkin D*, Pugh TJ. Fragmentomic analysis of cell-free DNA reveals cancer-asscoiated signatures in TP53 mutation carriers. Nature Communications Aug 27;15(1):7386. doi: 10.1038/s41467-024-51529-w. 2024

See a full list of David Malkin's publications