Photo of Henning Willers,  MD

Henning Willers, MD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-8162
Fax: (617) 724-8320


hwillers@mgh.harvard.edu

Henning Willers, MD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Radiation Oncology, Harvard Medical School
  • Associate Radiation Oncologist, Department of Radiation Oncology, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

I am a clinician-scientist with a special interest in the management of non-small cell lung cancer (NSCLC). My clinical efforts have focused on improving treatment outcomes for patients with this deadly disease. I have also been very active in radiation biology since 1991 and as a laboratory-based PI since 2005. My basic and translational research activities are directed at furthering our understanding of how NSCLCs respond to radiation and radiosensitizing drugs. Specifically, we seek to identify the signaling pathways that contribute to the radioresistance of KRAS-mutant lung adenocarcinoma which is an emerging clinical problem. This effort is funded by a grant from the American Cancer Society. We also have established a cancer cell line screening platform for precision radiation medicine. This project addresses an important need in the field to better understand the utility of known and novel radiosensitizing targeted agents in panels of annotated cancer cell lines that provide models of genetic tumor heterogeneity seen in patients. Eventually, these efforts are expected to yield correlations between genomic biomarkers and radiosensitizing agents that can be tested in clinical trials. Lastly, a distinct line of investigation involves the study of DNA repair pathways which are increasingly recognized to be altered in lung cancer. The goal of these studies is to establish genomic as well as functional protein biomarkers that will allow us to identify patients whose tumors will exhibit increased sensitivity to specific DNA damaging treatments, including proton beam radiation and PARP inhibitors. Together, these investigations are hoped to reveal novel therapeutic opportunities, including rational combinations of targeted agents with standard (photon) radiation or proton beam radiation, for personalized treatment of patients with NSCLC.

 

Publications

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  • Willers H, Stinchcombe TE, Barriger RB, Chetty IJ, Ginsburg ME, Kestin LL, Kumar S, Loo BW, Movsas B, Rimner A, Rosenzweig KE, Videtic GM, Chang JY, . ACR Appropriateness Criteria速 Induction and Adjuvant Therapy for N2 Non-small-cell Lung Cancer. Am J Clin Oncol 2015; 38:197-205. PubMed
  • Liu Q, Ghosh P, Magpayo N, Testa M, Tang S, Gheorghiu L, Biggs P, Paganetti H, Efstathiou JA, Lu HM, Held KD, Willers H. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation. Int J Radiat Oncol Biol Phys 2015; 91:1081-9. PubMed
  • Xiong X, Du Z, Wang Y, Feng Z, Fan P, Yan C, Willers H, Zhang J. 53BP1 promotes microhomology-mediated end-joining in G1-phase cells. Nucleic Acids Res 2015; 43:1659-70. PubMed
  • Liu Q, Wang M, Kern AM, Khaled S, Han J, Yeap BY, Hong TS, Settleman J, Benes CH, Held KD, Efstathiou JA, Willers H. Adapting a Drug Screening Platform to Discover Associations of Molecular Targeted Radiosensitizers with Genomic Biomarkers. Mol Cancer Res 2015. PubMed
  • Willers H, Hong TS. Towards an integrated understanding of epidermal growth factor receptor biology for radiation therapy: integrins enter. Journal of the National Cancer Institute 2015. PubMed
  • Mak KS, Gainor JF, Niemierko A, Oh KS, Willers H, Choi NC, Loeffler JS, Sequist LV, Shaw AT, Shih HA. Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases. 2014. PubMed
  • Wang M, Kern AM, Hülskötter M, Greninger P, Singh A, Pan Y, Chowdhury D, Krause M, Baumann M, Benes CH, Efstathiou JA, Settleman J, Willers H. EGFR-mediated chromatin condensation protects KRAS-mutant cancer cells against ionizing radiation. Cancer Res 2014. PubMed
  • Pfäffle HN, Wang M, Gheorghiu L, Ferraiolo N, Greninger P, Borgmann K, Settleman J, Benes CH, Sequist LV, Zou L, Willers H. EGFR-activating mutations correlate with a Fanconi anemia-like cellular phenotype that includes PARP inhibitor sensitivity. Cancer Res 2013; 73:6254-63. PubMed
  • Seco J, Gu G, Marcelos T, Kooy H, Willers H. Proton arc reduces range uncertainty effects and improves conformality compared with photon volumetric modulated arc therapy in stereotactic body radiation therapy for non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2013; 87:188-94. PubMed
  • Rosenzweig KE, Chang JY, Chetty IJ, Decker RH, Ginsburg ME, Kestin LL, Kong FM, Lally BE, Langer CJ, Movsas B, Videtic GM, Willers H. ACR appropriateness criteria nonsurgical treatment for non-small-cell lung cancer: poor performance status or palliative intent. J Am Coll Radiol 2013; 10:654-64. PubMed
  • Kong FM, Lally BE, Chang JY, Chetty IJ, Decker RH, Ginsburg ME, Kestin LL, Langer CJ, Movsas B, Videtic GM, Willers H, Rosenzweig KE, . ACR Appropriateness Criteria速 Radiation Therapy for Small-Cell Lung Cancer. Am J Clin Oncol 2013; 36:206-213. PubMed
  • Goldberg SB, Willers H, Heist RS. Multidisciplinary management of small cell lung cancer. Surg Oncol Clin N Am 2013; 22:329-43. PubMed
  • Birkelbach M, Ferraiolo N, Gheorghiu L, Pfäffle HN, Daly B, Ebright MI, Spencer C, O'Hara C, Whetstine JR, Benes CH, Sequist LV, Zou L, Dahm-Daphi J, Kachnic LA, Willers H. Detection of impaired homologous recombination repair in NSCLC cells and tissues. J Thorac Oncol 2013; 8:279-86. PubMed
  • Grassberger C, Dowdell S, Lomax A, Sharp G, Shackleford J, Choi N, Willers H, Paganetti H. Motion Interplay as a Function of Patient Parameters and Spot Size in Spot Scanning Proton Therapy for Lung Cancer. Int J Radiat Oncol Biol Phys 2013. PubMed
  • Westover KD, Seco J, Adams JA, Lanuti M, Choi NC, Engelsman M, Willers H. Proton SBRT for medically inoperable stage I NSCLC. J Thorac Oncol 2012; 7:1021-5. PubMed
  • Lanuti M, Sharma A, Willers H, Digumarthy SR, Mathisen DJ, Shepard JA. Radiofrequency ablation for stage I non-small cell lung cancer: management of locoregional recurrence. Ann Thorac Surg 2012; 93:921-8. PubMed
  • Mak RH, Alexander BM, Asomaning K, Heist RS, Liu CY, Su L, Zhai R, Ancukiewicz M, Napolitano B, Niemierko A, Willers H, Choi NC, Christiani DC. A single-nucleotide polymorphism in the MTHFR (methylene tetrahydrofolate reductase) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy. Cancer 2011. PubMed
  • Wang M, Morsbach F, Sander D, Gheorghiu L, Nanda A, Benes C, Kriegs M, Krause M, Dikomey E, Baumann M, Dahm-Daphi J, Settleman J, Willers H. EGF Receptor Inhibition Radiosensitizes NSCLC Cells by Inducing Senescence in Cells Sustaining DNA Double-Strand Breaks. Cancer Res 2011; 71:6261-9. PubMed
  • Kachnic LA, Li L, Fournier L, Ferraiolo N, Dahm-Daphi J, Borgmann K, Willers H. FANCD2 but not FANCA promotes cellular resistance to type II topoisomerase poisons. Cancer Lett 2011; 305:86-93. PubMed
  • Sirbu BM, Lachmayer SJ, Wülfing V, Marten LM, Clarkson KE, Lee LW, Gheorghiu L, Zou L, Powell SN, Dahm-Daphi J, Willers H. ATR-p53 restricts homologous recombination in response to replicative stress but does not limit DNA interstrand crosslink repair in lung cancer cells. PLoS ONE 2011; 6:e23053. PubMed
  • Mak RH, Doran E, Muzikansky A, Kang J, Neal JW, Baldini EH, Choi NC, Willers H, Jackman DM, Sequist LV. Outcomes after combined modality therapy for EGFR-mutant and wild-type locally advanced NSCLC. Oncologist 2011; 16:886-95. PubMed
  • Eichler AF, Kahle KT, Wang DL, Joshi VA, Willers H, Engelman JA, Lynch TJ, Sequist LV. EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. 2010; 12:1193-9. PubMed
  • Kachnic LA, Li L, Fournier L, Willers H. Fanconi Anemia pathway heterogeneity revealed by cisplatin and oxaliplatin treatments. Cancer Lett 2010; 292:73-9. PubMed
  • Zhuang J, Jiang G, Willers H, Xia F. Exonuclease function of human Mre11 promotes deletional nonhomologous end joining. J Biol Chem 2009; 284:30565-73. PubMed
  • Willers H, Taghian AG, Luo CM, Treszezamsky A, Sgroi DC, Powell SN. Utility of DNA repair protein foci for the detection of putative BRCA1 pathway defects in breast cancer biopsies. Mol Cancer Res 2009; 7:1304-9. PubMed
  • Kuhnert VM,Kachnic LA,Li L,Purschke M,Gheorghiu L,Lee R,Held KD,Willers H. FANCD2-deficient human fibroblasts are hypersensitive to ionising radiation at oxygen concentrations of 0% and 3% but not under normoxic conditions. Int J Radiat Biol 2009; 85:523-31. PubMed
  • Shi W,Ma Z,Willers H,Akhtar K,Scott SP,Zhang J,Powell S,Zhang J. Disassembly of MDC1 foci is controlled by ubiquitin-proteasome-dependent degradation. J Biol Chem 2008; 283:31608-16. PubMed
  • Nanda A,Dias-Santagata DC,Stubbs H,O'Hara CJ,Zaner KS,Lynch TJ,Willers H. Unusual tumor response and toxicity from radiation and concurrent erlotinib for non-small-cell lung cancer. Clin Lung Cancer 2008; 9:285-7. PubMed
  • Mansour WY,Schumacher S,Rosskopf R,Rhein T,Schmidt-Petersen F,Gatzemeier F,Haag F,Borgmann K,Willers H,Dahm-Daphi J. Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks. Nucleic Acids Res 2008; 36:4088-98. PubMed
  • Schulte-Uentrop L, El-Awady RA, Schliecker L, Willers H, Dahm-Daphi J. Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks. Nucleic Acids Res 2008; 36:2561-9. PubMed
  • Willers H, Husson J, Lee LW, Hubbe P, Gazemeier F, Powell SN, Dahm-Daphi J. Distinct mechanisms of nonhomologous end joining in the repair of site-directed chromosomal breaks with noncomplementary and complementary ends. Radiat Res 2006; 166:567-74. PubMed
  • Zhuang J, Zhang J, Willers H, Wang H, Chung JH, van Gent DC, Hallahan DE, Powell SN, Xia F. Checkpoint kinase 2-mediated phosphorylation of BRCA1 regulates the fidelity of nonhomologous end-joining. Cancer Res 2006; 66:1401-8. PubMed
  • Willers H, Held KD. Introduction to clinical radiation biology. Hematol Oncol Clin North Am 2006; 20:1-24. PubMed
  • Dahm-Daphi J, Hubbe P, Horvath F, El-Awady RA, Bouffard KE, Powell SN, Willers H. Nonhomologous end-joining of site-specific but not of radiation-induced DNA double-strand breaks is reduced in the presence of wild-type p53. Oncogene 2005; 24:1663-72. PubMed
  • Romanova LY, Willers H, Blagosklonny MV, Powell SN. The interaction of p53 with replication protein A mediates suppression of homologous recombination. Oncogene 2004; 23:9025-33. PubMed
  • Willers H, Dahm-Daphi J, Powell SN. Repair of radiation damage to DNA. Br J Cancer 2004; 90:1297-301. PubMed
  • Zhang J, Willers H, Feng Z, Ghosh JC, Kim S, Weaver DT, Chung JH, Powell SN, Xia F. Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair. Mol Cell Biol 2004; 24:708-18. PubMed
  • Willers H, Azzoli CG, Santivasi WL, Xia F. Basic mechanisms of therapeutic resistance to radiation and chemotherapy in lung cancer. Cancer J 2013; 19:200-7. PubMed
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