University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Alejandro Sweet-Cordero, MD

Alejandro Sweet-Cordero, MD

Associate Professor of Pediatrics, UCSF

Cancer Center Program Memberships

Pediatric Malignancies | Cancer Genetics

Research Summary

The goal of my laboratory is to identify novel therapeutic approaches for cancer that target the genetic mutations and altered signaling networks that are specific to cancer cells. We use functional genomics applied to mouse and human systems (genetically engineered models, patient derived xenografts) to understand the transcriptional networks that regulate the outcome of specific oncogenic mutations and to understand how cancers become resistant to chemotherapy. We have two primary disease interests: lung cancer and pediatric sarcomas. Our laboratory has identified novel regulators of chemoresistance in lung cancer (Oliver et al, 2010 Genes and Development). We have used functional genomics in mouse and human models to identify a novel role for Wt1 in mediating KRAS-driven oncogenesis (Vicent et al, 2010, JCI). We have identified and characterized the role of tumor-propagating cells in NSCLC and identified a key role for Notch3 as a self-renewal pathway in mouse and human NSCLC (Zheng et al, 2013, Cancer Cell). In our sarcoma work, we are interested in mechanisms driving osteosarcoma and Ewing sarcoma progression. We recently identified the first lncRNA involved in the pathogenesis of Ewing sarcoma (Howarth et al, JCI, 2014). We rely heavily on computational genomic analysis in our work and we have extensive experience in generating and using high-throughput datasets and next-generation sequencing for gene and network discovery. We are also actively involved in a multidisciplinary effort to apply next-generation sequencing (WGS/RNAseq etc) to advance the care of relapsed and other high-risk pediatric cancer patients at UCSF/Benioff Children’s Hospitals.

Education

Stanford University, B.S., 06/1989, Biology
Stanford University, B.A., 06/1989, Anthropology
University of California San Francisco, M.D., 06/1995, Medicine
University of California San Francisco, Residency, 06/1998, Pediatrics
Dana Farber Cancer Institute/Boston Children’s Hospital, Subspecialty training, 06/2002, Pediatric Hematology/Oncology


Professional Experience

  • 1998 – 1999
    Clinical Instructor, Department of Pediatrics. University of California San Francisco
  • 2000 - 2002
  • Research Fellow, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA
  • 2002-2005
    Clinical Instructor, Pediatric Hematology-Oncology, Children's Hospital/Dana-Farber Cancer Institute, Boston, MA
  • 2005-2012
    Assistant Professor of Pediatrics, Stanford University School of Medicine
  • 2013-2016
    Associate Professor of Pediatrics, Stanford University School of Medicine
  • 2017- present
    Associate Professor of Pediatrics, University of California San Francisco

Honors & Awards

  • 1989
    Stanford University Firestone Award for Excellence in Undergraduate Research
  • 2006
    Sidney Kimmel Scholar Award
  • 2007
    Doris Duke Clinical Scientist Award
  • 2008
    Rita Allen Scholar Award
  • 2009
    Morgridge Scholar Award

Selected Publications

  1. Hsieh G, Bierman R, Szabo L, Lee AG, Freeman DE, Watson N, Sweet-Cordero EA, Salzman J. Statistical algorithms improve accuracy of gene fusion detection. Nucleic Acids Res. 2017 Jul 27; 45(13):e126.
    View on PubMed
  2. Alvarez E, Seppa M, Rivas S, Fuentes L, Valverde P, Antillón-Klussmann F, Castellanos M, Sweet-Cordero EA, Messacar K, Kurap J, Bustamante M, Howard SC, Efron B, Luna-Fineman S. Improvement in treatment abandonment in pediatric patients with cancer in Guatemala. Pediatr Blood Cancer. 2017 Oct; 64(10).
    View on PubMed
  3. Vallejo A, Perurena N, Guruceaga E, Mazur PK, Martinez-Canarias S, Zandueta C, Valencia K, Arricibita A, Gwinn D, Sayles LC, Chuang CH, Guembe L, Bailey P, Chang DK, Biankin A, Ponz-Sarvise M, Andersen JB, Khatri P, Bozec A, Sweet-Cordero EA, Sage J, Lecanda F, Vicent S. An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer. Nat Commun. 2017 Feb 21; 8:14294.
    View on PubMed
  4. Chuang CH, Greenside PG, Rogers ZN, Brady JJ, Yang D, Ma RK, Caswell DR, Chiou SH, Winters AF, Grüner BM, Ramaswami G, Spencley AL, Kopecky KE, Sayles LC, Sweet-Cordero EA, Li JB, Kundaje A, Winslow MM. Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis. Nat Med. 2017 Mar; 23(3):291-300.
    View on PubMed
  5. Brady JJ, Chuang CH, Greenside PG, Rogers ZN, Murray CW, Caswell DR, Hartmann U, Connolly AJ, Sweet-Cordero EA, Kundaje A, Winslow MM. An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency. Cancer Cell. 2016 05 09; 29(5):697-710.
    View on PubMed
  6. Mazur PK, Herner A, Mello SS, Wirth M, Hausmann S, Sánchez-Rivera FJ, Lofgren SM, Kuschma T, Hahn SA, Vangala D, Trajkovic-Arsic M, Gupta A, Heid I, Noël PB, Braren R, Erkan M, Kleeff J, Sipos B, Sayles LC, Heikenwalder M, Heßmann E, Ellenrieder V, Esposito I, Jacks T, Bradner JE, Khatri P, Sweet-Cordero EA, Attardi LD, Schmid RM, Schneider G, Sage J, Siveke JT. Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. Nat Med. 2015 Oct; 21(10):1163-71.
    View on PubMed
  7. Marques Howarth M, Simpson D, Ngok SP, Nieves B, Chen R, Siprashvili Z, Vaka D, Breese MR, Crompton BD, Alexe G, Hawkins DS, Jacobson D, Brunner AL, West R, Mora J, Stegmaier K, Khavari P, Sweet-Cordero EA. Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis. J Clin Invest. 2014 Dec; 124(12):5275-90.
    View on PubMed
  8. Chen R, Khatri P, Mazur PK, Polin M, Zheng Y, Vaka D, Hoang CD, Shrager J, Xu Y, Vicent S, Butte AJ, Sweet-Cordero EA. A meta-analysis of lung cancer gene expression identifies PTK7 as a survival gene in lung adenocarcinoma. Cancer Res. 2014 May 15; 74(10):2892-902.
    View on PubMed
  9. Valdmanis PN, Roy-Chaudhuri B, Kim HK, Sayles LC, Zheng Y, Chuang CH, Caswell DR, Chu K, Zhang Y, Winslow MM, Sweet-Cordero EA, Kay MA. Upregulation of the microRNA cluster at the Dlk1-Dio3 locus in lung adenocarcinoma. Oncogene. 2015 Jan 02; 34(1):94-103.
    View on PubMed
  10. Zheng Y, de la Cruz CC, Sayles LC, Alleyne-Chin C, Vaka D, Knaak TD, Bigos M, Xu Y, Hoang CD, Shrager JB, Fehling HJ, French D, Forrest W, Jiang Z, Carano RA, Barck KH, Jackson EL, Sweet-Cordero EA. A rare population of CD24(+)ITGB4(+)Notch(hi) cells drives tumor propagation in NSCLC and requires Notch3 for self-renewal. Cancer Cell. 2013 Jul 08; 24(1):59-74.
    View on PubMed
  11. Chen R, Sweet-Cordero EA. Two is better than one: combining IGF1R and MEK blockade as a promising novel treatment strategy against KRAS-mutant lung cancer. Cancer Discov. 2013 May; 3(5):491-3.
    View on PubMed
  12. Gwinn D, Sweet-Cordero EA. The phosphatase PP2A links glutamine to the tumor suppressor p53. Mol Cell. 2013 Apr 25; 50(2):157-8.
    View on PubMed
  13. Zheng Y, Moore H, Piryatinska A, Solis T, Sweet-Cordero EA. Mathematical modeling of tumor cell proliferation kinetics and label retention in a mouse model of lung cancer. Cancer Res. 2013 Jun 15; 73(12):3525-33.
    View on PubMed
  14. Hegde GV, de la Cruz CC, Chiu C, Alag N, Schaefer G, Crocker L, Ross S, Goldenberg D, Merchant M, Tien J, Shao L, Roth L, Tsai SP, Stawicki S, Jin Z, Wyatt SK, Carano RA, Zheng Y, Sweet-Cordero EA, Wu Y, Jackson EL. Blocking NRG1 and other ligand-mediated Her4 signaling enhances the magnitude and duration of the chemotherapeutic response of non-small cell lung cancer. Sci Transl Med. 2013 Feb 06; 5(171):171ra18.
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  15. Hegde GV, de la Cruz C, Eastham-Anderson J, Zheng Y, Sweet-Cordero EA, Jackson EL. Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity. PLoS One. 2012; 7(10):e45647.
    View on PubMed
  16. Vicent S, Sayles LC, Vaka D, Khatri P, Gevaert O, Chen R, Zheng Y, Gillespie AK, Clarke N, Xu Y, Shrager J, Hoang CD, Plevritis S, Butte AJ, Sweet-Cordero EA. Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL-6 in non-small cell lung cancer in vivo. Cancer Res. 2012 Nov 15; 72(22):5744-56.
    View on PubMed
  17. Vicent S, Chen R, Sayles LC, Lin C, Walker RG, Gillespie AK, Subramanian A, Hinkle G, Yang X, Saif S, Root DE, Huff V, Hahn WC, Sweet-Cordero EA. Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models. J Clin Invest. 2010 Nov; 120(11):3940-52.
    View on PubMed
  18. Schaffer BE, Park KS, Yiu G, Conklin JF, Lin C, Burkhart DL, Karnezis AN, Sweet-Cordero EA, Sage J. Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma. Cancer Res. 2010 May 15; 70(10):3877-83.
    View on PubMed
  19. Oliver TG, Mercer KL, Sayles LC, Burke JR, Mendus D, Lovejoy KS, Cheng MH, Subramanian A, Mu D, Powers S, Crowley D, Bronson RT, Whittaker CA, Bhutkar A, Lippard SJ, Golub T, Thomale J, Jacks T, Sweet-Cordero EA. Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer. Genes Dev. 2010 Apr 15; 24(8):837-52.
    View on PubMed
  20. Sweet-Cordero A, Tseng GC, You H, Douglass M, Huey B, Albertson D, Jacks T. Comparison of gene expression and DNA copy number changes in a murine model of lung cancer. Genes Chromosomes Cancer. 2006 Apr; 45(4):338-48.
    View on PubMed

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