Alejandro Sweet-Cordero, MD
Associate Professor of Pediatrics
Stanford University School of Medicine

Phone: (650) 725 5901

Lab Contact Information:
265 Campus Drive
LLSCR Building, Rm. G2078b
Stanford, CA, 94305
Phone: (650) 736 2753
Fax : 650 736 0195

Reseach Overview

Our laboratory focuses on the analysis of pathways involved in the initiation, progression, and maintenance of cancer. We use genetically engineered mouse models and primary human tumor samples to interrogate specific tumor types and understand key aspects of their biology. Our current disease focus includes lung cancer and pediatric bone sarcomas (Ewing’s and Osteosarcoma). We rely on functional genomic approaches (RNAseq, DNAseq, microarrays, shRNA screens) to identify genes that are relevant to cancer pathogenesis and treatment. We have pioneered approaches for cross-species genomic analysis (Sweet-Cordero et al. Nature Genetics, 2005), which we have found to be a useful tool to identify and characterize novel critical regulators of oncogenesis. Using a cross-species functional genomic approach we identified a synthetic lethal interaction between oncogenic Kras and loss of the Wt1 gene (Vicent et al. Journal of Clinical Investigation, 2010). We have also identified a novel cross-talk mechanism between cancer-associated fibroblasts and tumor cells, underscoring the utility of mouse models to study the cancer microenvironment (Vicent et al. Cancer Research, 2012).

We are interested in studying tumor heterogeneity and determining whether "cancer stem cells" also known as “tumor propagating cells" (TPCs) play a role in driving chemoresistance and tumor progression in vivo. We have found that mouse models can be used to identify novel mechanisms of chemotherapy response and elucidate the contribution of specific mutations to chemotherapy resistance (Oliver et al. Genes and Development, 2010). Using these mouse models, we have identified a subpopulation of tumor cells that are enriched for TPCs (Zheng et al. Cancer Cell, 2013). This TPC population is also increased in frequency after repeated treatment with chemotherapy in vivo, suggesting that TPCs are chemoresistant. Further analysis of the signaling pathways that drive TPCs proliferation and self-renewal are actively being pursued in the laboratory. Key to our studies is the ability to leverage mouse genetics with analysis of primary human lung cancer samples (PDX), a significant collection of which is available in our laboratory.

In the area of sarcoma research, we have developed one of the first models for activation of the EWS/FLI-1 oncogene in a murine model system and are currently testing this system for identification of critical regulators of EWS/FLI-1 driven oncogenesis. Working with our orthopedic surgeon colleagues at Stanford and collaborators at UCSF and UW, we have established a large collection of patient-derived xenografts from both osteosarcoma and Ewing sarcoma, tools that are being used in the laboratory to identify and characterize genes relevant to the pathogenesis of these diseases. Lastly, our laboratory is leading efforts to test the utility of genome sequencing (targeted exome, WGS) for care of patients with advanced or relapsed sarcomas. This involves applying advanced sequencing approaches (RNAseq, WGS, WES, CAPPseq, etc.) to patient samples and using this information to guide therapy decisions.

Current research efforts are focused on:

  • - Role of Notch signaling in lung cancer
    • - Mechanism of oncogenic Kras signaling (synthetic lethality)
    - chemotherapy resistance in lung cancer TPCs
  • - Role of lncRNAs and other novel targets in Ewing sarcoma
  • - Identification of TPCs and characterization of tumor heterogeneity in Osteosarcoma

A more detailed description of current research projects can be found in the research section.