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Targeting chemotherapy resistance in mesenchymal triple-negative breast cancer: a phase II trial of neoadjuvant angiogenic and mTOR inhibition with chemotherapy

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Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Nour Abuhadra, Alyson R. Clayborn, Jason B. White, Elizabeth E. Ravenberg, Banu Arun, Senthil Damodaran, Kimberly B. Koenig, Rachel M. Layman, Bora Lim, Jennifer K. Litton, Naoto T. Ueno, Gabriel N. Hortobagyi, Vicente Valero, Debu Tripathy, Stacy Moulder & Clinton Yam

  2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ryan Sun & Roland L. Bassett Jr

  3. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Lei Huo, Qingqing Ding & W. Fraser Symmans

  4. Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Jeffrey T. Chang

  5. Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Mediget Teshome & Alastair Thompson

  6. Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Beatriz E. Adrada, Rosalind P. Candelaria, Wei Yang & Gaiane M. Rauch

  7. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Helen Piwnica-Worms

Authors
  1. Nour Abuhadra
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  2. Ryan Sun
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Contributions

Nour Abuhadra: Investigation, Data Curation, Writing – Original Draft, Writing – Review & Editing, Visualization. Ryan Sun: Software, Formal Analysis, Writing – Review & Editing. Roland L. Bassett Jr: Software, Formal Analysis, Writing – Review & Editing. Lei Huo: Methodology, Investigation, Data Curation, Writing – Review & Editing, Supervision. Jeffrey T. Chang: Software, Formal Analysis, Writing – Review & Editing. Mediget Teshome: Investigation, Data Curation, Writing – Review & Editing. Alyson R. Clayborn: Data Curation, Writing – Review & Editing, Project Administration. Jason B. White: Data Curation, Writing – Review & Editing, Project Administration. Elizabeth E. Ravenberg: Data Curation, Writing – Review & Editing, Project Administration. Beatriz E. Adrada: Investigation, Data Curation, Writing – Review & Editing. Rosalind P. Candelaria: Investigation, Data Curation, Writing – Review & Editing. Wei Yang: Conceptualization, Investigation, Data Curation, Writing – Review & Editing. Qingqing Ding: Investigation, Data Curation, Writing – Review & Editing. W. Fraser Symmans: Conceptualization, Investigation, Data Curation, Writing – Review & Editing. Banu Arun: Investigation, Data Curation, Writing – Review & Editing. Senthil Damodaran: Investigation, Data Curation, Writing – Review & Editing. Kimberly B. Koenig: Investigation, Data Curation, Writing – Review & Editing. Rachel M. Layman: Investigation, Data Curation, Writing – Review & Editing. Bora Lim: Investigation, Data Curation, Writing – Review & Editing. Jennifer K. Litton: Conceptualization, Investigation, Data Curation, Writing – Review & Editing. Alastair Thompson: Conceptualization, Investigation, Data Curation, Writing – Review & Editing. Naoto T. Ueno: Conceptualization, Investigation, Data Curation, Writing – Review & Editing. Helen Piwnica-Worms: Conceptualization, Investigation, Data Curation, Writing – Review & Editing. Gabriel N. Hortobagyi: Conceptualization, Investigation, Data Curation, Writing – Review & Editing. Vicente Valero: Conceptualization, Investigation, Data Curation, Writing – Review & Editing, Supervision. Debu Tripathy: Conceptualization, Investigation, Data Curation, Writing – Review & Editing, Supervision. Gaiane M. Rauch: Conceptualization, Investigation, Data Curation, Writing – Review & Editing, Supervision. Stacy Moulder: Conceptualization, Methodology, Formal Analysis. Investigation, Resources, Data Curation, Writing – Original Draft, Writing – Review & Editing, Visualization, Supervision., Project administration, Funding acquisition. Clinton Yam: Formal Analysis. Investigation, Resources, Data Curation, Writing – Original Draft, Writing – Review & Editing, Visualization, Supervision, Project administration.

Corresponding authors

Correspondence to Stacy Moulder or Clinton Yam.

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Conflict of interest

E.E.R. is currently employed at Eli Lilly (previously employed by MD Anderson at the time the study was conducted). W.F.S. is a co-inventor/patent of US Patent No. 11,459,617 “Targeted measure of transcriptional activity related to hormone receptors” issued on 10/4/2022 (applicant proprietor: University of Texas MD Anderson Cancer Center. Licensed to Delphi Diagnostics, Inc. and has co-founder equity from Delphi Diagnostics, Inc. R.L. has received research funding (to the institution) from Novartis and serves on the advisory board for Novartis. J.K.L. has received grant or research support from Novartis, Medivation/Pfizer, Genentech, GSK, EMD-Serono, Astra-Zeneca, Medimmune, Zenith, Jounce; participated in Speaker’s Bureau for MedLearning, Physician’s Education Resource, Prime Oncology, Medscape, Clinical Care Options; received honoraria from UpToDate; served on advisory committees or review panels for Astra-Zeneca, Ayala, Pfizer (all uncompensated), NCCN, ASCO, NIH, PDQ, SITC Breast Committee, SWOG Breast Committee. A.T. is related by marriage to an employee of Eli Lilly. D.T. has received research support (to the institution) from Novartis, Pfizer, Polyphor and has served as a consultant to AstraZeneca, Glaxosmithkline, Gilead, Oncopep, Pfizer, Novartis, AMBRX, Personalis, Sermonix, Stemline-Menarini, Puma Biotechnology. S.L.M. is currently employed by Eli Lilly (previously employed by MD Anderson at the time the study was conducted). All other authors declare that they have no relevant conflicts of interest. C.Y. has received research funding (to the institution) from Genentech, Gilead, BostonGene, Sanofi, Amgen, Pfizer, Astellas, Novartis and has served on advisory boards for Gilead. All other authors declare no relevant conflicts of interest.

Financial support

Funding and drug support were provided (in part) by Novartis AG; Pfizer Inc. This work was funded by generous philanthropic contributions to the Moon Shots Program of The University of Texas MD Anderson Cancer Center, the Still Water Foundation (to D. Tripathy), and the Winterhof fund (to S.L. Moulder). Pre-sequencing processing work was completed by the Cancer Genomics Laboratory Moon Shots Platform and the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy at The University of Texas MD Anderson Cancer Center. Sequencing and data generation was supported by the CA016672 grant from The University of Texas MD Anderson Cancer Center. Dr. Yam was additionally supported by a Conquer Cancer Career Development Award supported by Fleur Fairman, the 2018 Gianni Bonadonna Breast Cancer Research Fellowship (Conquer Cancer Foundation), the Allison and Brian Grove Endowed Fellowship for Breast Medical Oncology, and the Susan Papizan Dolan Fellowship in Breast Oncology. Dr. Chang was supported by the Cancer Prevention Research Institute of Texas (RP170668, RP160710) and the National Institutes of Health’s National Cancer Institute (U54CA209978). Any opinions, findings, and conclusions expressed in this material are those of the author(s) and do not necessarily reflect those of the sponsors.

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Abuhadra, N., Sun, R., Bassett, R.L. et al. Targeting chemotherapy resistance in mesenchymal triple-negative breast cancer: a phase II trial of neoadjuvant angiogenic and mTOR inhibition with chemotherapy. Invest New Drugs 41, 391–401 (2023). https://doi.org/10.1007/s10637-023-01357-4

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