Cristina Antonescu graduated from Carol Davila Medical School, Bucharest, Romania in 1992. She started her Anatomic Pathology training at the same university in Bucharest between 1992-1994, before coming to US. She finished her Residency in Anatomic Pathology in 1996 at Lenox Hill Hospital in New York, and then enrolled in an Oncologic Pathology Fellowship at Memorial Sloan-Kettering Cancer Center (MSKCC) under Dr. Juan Rosai. She then stayed an additional year as a chief fellow, before joining Dr. Marc Ladanyi’s lab as a sarcoma research fellow. During the time spent in the lab she acquired basic molecular skills related to detection and characterization of fusion transcripts in translocation-associated sarcomas. In 1999, she joined the staff of the Pathology Department at MSKCC as an Assistant Attending Pathologist. Her academic career in bone and soft tissue pathology was guided by the close mentorship of two historical figures, Drs. Andrew Huvos and James Woodruff.
While being on full clinical duties she continued her bench-work research in Dr Peter Besmer laboratory. Dr Besmer, professor in the Developmental Biology Program at Sloan-Kettering Institute, has originally isolated the v-kit oncogene and has done seminal work in KIT-induced signal transduction. As a result of his mentorship and collaborative effort, Dr Antonescu obtained in 2004 an American Carcer Society KO8 award to study the molecular mechanisms of oncogenesis in gastrointestinal stromal tumors (GIST), an interest of hers that continues today. She was instrumental in characterizing the first mouse model of GIST. Her work has lead to major contributions to the field, such as: understanding the clinical impact of oncogenic KIT mutations in GIST; characterization of pathologic and molecular heterogeneity in imatinib-stable or imatinib-responsive GIST; define mechanisms of tumor progression and resistance to tyrosine kinase inhibitors; molecular characterization of pediatric GIST; novel V600E BRAF mutations in imatinib-naive and imatinib-resistant GIST; establishing a novel in-vitro screening method for 2nd generation kinase inhibitors on a library of genetically engineered cell lines harboring imatinib sensitive single KIT mutations, as well as imatinib-resistant double KIT mutations. In 2006 she received the Boyer Clinical Award from Memorial Sloan-Kettering Cancer Center, in recognition for her accomplishments and to support her ongoing work on GIST.
The other scope of her research focused on the molecular characterization of novel fusion genes, which may serve as specific molecular markers in diagnosis and prognosis of soft tissue and bone tumors, as well as potential therapeutic targets. A number of these discoveries were done in close collaborative effort with Drs. Christopher Fletcher and Paola dal Cin from Brigham & Women Hospital. Just to name a few: the identification of EWSR1-CREB1, as a novel variant translocation in the majority of clear cell sarcoma of the gastrointestinal tract and angiomatoid fibrous histiocytoma; the molecular classification of soft tissue and bone myoepithelial tumors, showing common involvement of EWSR1 rearrangement and characterization of a novel EWRS1-POUF1 fusion in a subset of tumors; identification of a new WWTR1-CAMTA1 gene fusion as a consistent genetic abnormality in epithelioid hemangioendothelioma of different anatomic sites as well as demonstrating the monoclonality of multifocal lesions; identification of a consistent t(1;10) translocation, with rearrangements of TGFBR3 and MGEA5, in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor, suggesting a common pathogenesis of these lesions showing a distinct morphologic appearance; and more recently a high prevalence of CIC-DUX4 fusion in EWSR1-negative small blue round cell tumors.
The expertise and productivity of Dr Antonescu sarcoma research lab has played a significant role in the success of the sarcoma research program at MSKCC. The Center has been recognized as a leader in sarcoma research by the NCI, which has supported MSKCC with Soft Tissue Sarcoma Program Project Grants. In further recognition of the integrated Institutional efforts, the NCI awarded its first ever Specialized Program of Research Excellence (SPORE) grant for soft tissue sarcoma to MSKCC. The five-year (07/01/10-06/30/15), $11.5 million grant funds research aimed at developing an integrated multidisciplinary investigation of the biology, pathogenesis, progression, and natural history of sarcoma. As a co-leader of one of the projects, her lab will apply genomic approaches to identify alternative therapeutic candidates and signaling pathways in wild-type GIST and in imatinib-resistant GIST lacking an identifiable mechanism of resistance.
Dr Antonescu is an Attending Pathologist and Member on the tenure track at MSKCC and she serves as the chief of bone and soft tissue pathology service. Her sarcoma research laboratory serves as an invaluable resource in mentoring young investigators and pathology fellows, with a special interest in sarcoma pathology and molecular biology. As if these chores are not enough, she has served and continues to serve as a central pathology reviewer for multi-institutional sarcoma clinical trials.
She is keen in dedicating this award to the remarkable mentors who have helped her achieve such an accomplished academic career: Drs Constantin Tasca, Juan Rosai, Andrew Huvos, James Woodruff, Marc Ladanyi, Peter Besmer, Murray Brennan and Christopher Fletcher. She also wants to thank her closest colleagues and collaborators: Paola dal Cin, Pedram Argani, Enrique de Alava, Ilan Weinreb, Julia Bridge, Jean-Michel Coindre, Narsi Agaram, and Meera Hameed.