Photo of Seth A. Wander,  MD, PhD

Seth A. Wander, MD, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-6500

Seth A. Wander, MD, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Instructor, Medicine, Harvard Medical School
  • Clinical Assistant in Medicine, Medicine, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

I am interested in the genomic and molecular mechanisms underlying resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in hormone-receptor positive (HR+) metastatic breast cancer. These agents have become the standard of care in this disease, but we have little insight into the mechanisms governing response or resistance in human patients. We have been utilizing next-generation sequencing (primarily whole exome) in collaboration with our colleagues at the Broad Institute to identify putative drivers in resistant tumor biopsies. Our work has led to the identification of multiple novel mediators of resistance, which we have been validating in the laboratory in vitro. It is our hope that these results will be readily translatable to the clinic, as many of these novel resistance mediators are actionable.

Publications

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  • Wander SA, Han HS, Zangardi ML, Niemierko A, Mariotti V, Kim LSL, Xi J, Pandey A, Dunne S, Nasrazadani A, Kambadakone A, Stein C, Lloyd MR, Yuen M, Spring LM, Juric D, Kuter I, Sanidas I, Moy B, Mulvey T, Vidula N, Dyson NJ, Ellisen LW, Isakoff S, Wagle N, Brufsky A, Kalinsky K, Ma CX, O'Shaughnessy J, Bardia A. Clinical Outcomes With Abemaciclib After Prior CDK4/6 Inhibitor Progression in Breast Cancer: A Multicenter Experience. J Natl Compr Canc Netw 2021. PubMed
  • Vidula N, Niemierko A, Malvarosa G, Yuen M, Lennerz JK, Iafrate AJ, Wander SA, Spring LM, Juric D, Isakoff SJ, Younger J, Moy B, Ellisen LW, Bardia A. Tumor tissue- versus plasma-based genotyping for selection of matched therapy and impact on clinical outcomes in patients with metastatic breast cancer. Clin Cancer Res 2021. PubMed
  • Mao P, Cohen O, Kowalski KJ, Kusiel JG, Buendia-Buendia JE, Cuoco MS, Exman P, Wander SA, Waks AG, Nayar U, Chung J, Freeman S, Rozenblatt-Rosen O, Miller VA, Piccioni F, Root DE, Regev A, Winer EP, Lin NU, Wagle N. Acquired FGFR and FGF Alterations Confer Resistance to Estrogen Receptor (ER) Targeted Therapy in ER Metastatic Breast Cancer. Clin Cancer Res 2020. PubMed
  • Vidula N, Dubash TD, Lawrence MS, Simoneau A, Niemierko A, Blouch EL, Nagy RJ, Roh W, Chirn B, Reeves B, Malvarosa G, Lennerz JK, Isakoff SJ, Juric D, Micalizzi DS, Wander SA, Spring LM, Moy B, Shannon KM, Younger J, Lanman RB, Toner M, Iafrate AJ, Getz G, Zou L, Ellisen LW, Maheswaran S, Haber DA, Bardia A. Identification of somatically acquired BRCA1/2 mutations by cfDNA analysis in patients with metastatic breast cancer. Clin Cancer Res 2020. PubMed
  • Wander SA, Cohen O, Gong X, Johnson GN, Buendia-Buendia JE, Lloyd MR, Kim D, Luo F, Mao P, Helvie K, Kowalski KJ, Nayar U, Waks AG, Parsons SH, Martinez R, Litchfield LM, Ye XS, Yu C, Jansen VM, Stille JR, Smith PS, Oakley GJ, Chu QS, Batist G, Hughes ME, Kremer JD, Garraway LA, Winer EP, Tolaney SM, Lin NU, Buchanan SG, Wagle N. The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4/6 inhibitors in patients with hormone receptor positive metastatic breast cancer. 2020. PubMed
  • Spring LM, Wander SA, Andre F, Moy B, Turner NC, Bardia A. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future. Lancet 2020; 395:817-827. PubMed
  • Drago JZ, Formisano L, Juric D, Niemierko A, Servetto A, Wander SA, Spring LM, Vidula N, Younger J, Peppercorn J, Yuen M, Malvarosa G, Sgroi D, Isakoff SJ, Moy B, Ellisen LW, Iafrate AJ, Arteaga CL, Bardia A. Amplification Mediates Endocrine Resistance but Retains TORC Sensitivity in Metastatic Hormone Receptor-Positive (HR) Breast Cancer. Clin Cancer Res 2019. PubMed
  • Wander SA, Spring LM, Bardia A. Genetics to epigenetics: targeting histone deacetylases in hormone receptor-positive metastatic breast cancer. Lancet Oncol. 2019; 20:746-748. PubMed
  • Cornell L, Wander SA, Visal T, Wagle N, Shapiro GI. MicroRNA-Mediated Suppression of the TGF-β Pathway Confers Transmissible and Reversible CDK4/6 Inhibitor Resistance. Cell Rep 2019; 26:2667-2680.e7. PubMed
  • Spring LM, Wander SA, Zangardi M, Bardia A. CDK 4/6 Inhibitors in Breast Cancer: Current Controversies and Future Directions. Curr Oncol Rep 2019; 21:25. PubMed
  • Nayar U, Cohen O, Kapstad C, Cuoco MS, Waks AG, Wander SA, Painter C, Freeman S, Persky NS, Marini L, Helvie K, Oliver N, Rozenblatt-Rosen O, Ma CX, Regev A, Winer EP, Lin NU, Wagle N. Acquired HER2 mutations in ER metastatic breast cancer confer resistance to estrogen receptor-directed therapies. Nat Genet 2018. PubMed
  • Wander SA, Mayer EL, Burstein HJ. Blocking the Cycle: Cyclin-Dependent Kinase 4/6 Inhibitors in Metastatic, Hormone Receptor-Positive Breast Cancer. J Clin Oncol 2017. PubMed
  • Wander SA, Zhao D, Besser AH, Hong F, Wei J, Ince TA, Milikowski C, Bishopric NH, Minn AJ, Creighton CJ, Slingerland JM. PI3K/mTOR inhibition can impair tumor invasion and metastasis in vivo despite a lack of antiproliferative action in vitro: implications for targeted therapy. Breast Cancer Res Treat 2018; 138:369-81. PubMed
  • Wander SA, Hennessy BT, Slingerland JM. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy. J Clin Invest 2018; 121:1231-41. PubMed
  • Wander SA, Zhao D, Slingerland JM. p27: a barometer of signaling deregulation and potential predictor of response to targeted therapies. Clin Cancer Res 2018; 17:12-8. PubMed
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