Doxycycline in Cutaneous Schwannoma (NF2)

Summary

In this research study the investigators want to learn more about an alternate, local treatment for skin schwannomas. Specifically, local doxycycline intra-tumoral injection will be performed as a potential treatment for NF2-related skin schwannomas, ultimately reducing the risks and costs associated with standard surgical removal of such skin tumors if successful.

Timeline

Start

2022-09-19

Primary completion

2026-09-01

Completion

2026-12

Publications

• Background Ren Y, Chari DA, Vasilijic S, Welling DB, Stankovic KM. New developments in neurofibromatosis type 2 and vestibular schwannoma. Neurooncol Adv. 2020 Nov 16;3(1):vdaa153. doi: 10.1093/noajnl/vdaa153. eCollection 2021 Jan-Dec.
• Background Evans DG. Neurofibromatosis type 2 (NF2): a clinical and molecular review. Orphanet J Rare Dis. 2009 Jun 19;4:16. doi: 10.1186/1750-1172-4-16.
• Background Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018. Neuro Oncol. 2021 Oct 5;23(12 Suppl 2):iii1-iii105. doi: 10.1093/neuonc/noab200.
• Background Balasubramaniam A, Shannon P, Hodaie M, Laperriere N, Michaels H, Guha A. Glioblastoma multiforme after stereotactic radiotherapy for acoustic neuroma: case report and review of the literature. Neuro Oncol. 2007 Oct;9(4):447-53. doi: 10.1215/15228517-2007-027. Epub 2007 Aug 17.
• Background Coy S, Rashid R, Stemmer-Rachamimov A, Santagata S. Correction to: An update on the CNS manifestations of neurofibromatosis type 2. Acta Neuropathol. 2020 Apr;139(4):667. doi: 10.1007/s00401-019-02044-6.
• Background Petrilli AM, Garcia J, Bott M, Klingeman Plati S, Dinh CT, Bracho OR, Yan D, Zou B, Mittal R, Telischi FF, Liu XZ, Chang LS, Welling DB, Copik AJ, Fernandez-Valle C. Ponatinib promotes a G1 cell-cycle arrest of merlin/NF2-deficient human schwann cells. Oncotarget. 2017 May 9;8(19):31666-31681. doi: 10.18632/oncotarget.15912.
• Background Cosetti MK, Golfinos JG, Roland JT Jr. Quality of Life (QoL) Assessment in Patients with Neurofibromatosis Type 2 (NF2). Otolaryngol Head Neck Surg. 2015 Oct;153(4):599-605. doi: 10.1177/0194599815573002. Epub 2015 Mar 16.
• Background Marchi E, Teixeira LR, Vargas FS. Management of malignancy-associated pleural effusion: current and future treatment strategies. Am J Respir Med. 2003;2(3):261-73. doi: 10.1007/BF03256654.
• Background Godfrey KJ, Kally P, Dunbar KE, Campbell AA, Callahan AB, Lo C, Freund R, Lisman RD. Doxycycline Injection for Sclerotherapy of Lower Eyelid Festoons and Malar Edema: Preliminary Results. Ophthalmic Plast Reconstr Surg. 2019 Sep/Oct;35(5):474-477. doi: 10.1097/IOP.0000000000001332.
• Background Shaye DA, Burks CA, Gadkaree SK, Ncogoza I, Tuyishimire G, Nyabyenda V, Gassore A. Self-compounded Doxycycline Sclerotherapy for the Treatment of Lymphatic Malformations in Low-Resource Settings. World J Surg. 2020 Nov;44(11):3616-3619. doi: 10.1007/s00268-020-05667-z. Epub 2020 Jul 8.
• Background Farnoosh S, Don D, Koempel J, Panossian A, Anselmo D, Stanley P. Efficacy of doxycycline and sodium tetradecyl sulfate sclerotherapy in pediatric head and neck lymphatic malformations. Int J Pediatr Otorhinolaryngol. 2015 Jun;79(6):883-887. doi: 10.1016/j.ijporl.2015.03.024. Epub 2015 Apr 6.
• Background Tang SJ, Sreenarasimhaiah J, Tang L, Rollins N, Purdy PD. Endoscopic injection sclerotherapy with doxycycline for mediastinal and esophageal lymphangiohemangioma. Gastrointest Endosc. 2007 Dec;66(6):1196-200. doi: 10.1016/j.gie.2007.06.023.
• Background Woon JTK, Hoon D, Graydon A, Flint M, Doyle AJ. Aneurysmal bone cyst treated with percutaneous doxycycline: is a single treatment sufficient? Skeletal Radiol. 2019 May;48(5):765-771. doi: 10.1007/s00256-019-03188-y. Epub 2019 Feb 26.
• Background Zhu C, Yan X, Yu A, Wang Y. Doxycycline synergizes with doxorubicin to inhibit the proliferation of castration-resistant prostate cancer cells. Acta Biochim Biophys Sin (Shanghai). 2017 Nov 1;49(11):999-1007. doi: 10.1093/abbs/gmx097.
• Background Alsaadi M, Tezcan G, Garanina EE, Hamza S, McIntyre A, Rizvanov AA, Khaiboullina SF. Doxycycline Attenuates Cancer Cell Growth by Suppressing NLRP3-Mediated Inflammation. Pharmaceuticals (Basel). 2021 Aug 26;14(9):852. doi: 10.3390/ph14090852.
• Background Nicoud IB, Jones CM, Pierce JM, Earl TM, Matrisian LM, Chari RS, Gorden DL. Warm hepatic ischemia-reperfusion promotes growth of colorectal carcinoma micrometastases in mouse liver via matrix metalloproteinase-9 induction. Cancer Res. 2007 Mar 15;67(6):2720-8. doi: 10.1158/0008-5472.CAN-06-3923.
• Background Sagar J, Sales K, Taanman JW, Dijk S, Winslet M. Lowering the apoptotic threshold in colorectal cancer cells by targeting mitochondria. Cancer Cell Int. 2010 Sep 6;10:31. doi: 10.1186/1475-2867-10-31.
• Background Tan Q, Yan X, Song L, Yi H, Li P, Sun G, Yu D, Li L, Zeng Z, Guo Z. Induction of Mitochondrial Dysfunction and Oxidative Damage by Antibiotic Drug Doxycycline Enhances the Responsiveness of Glioblastoma to Chemotherapy. Med Sci Monit. 2017 Aug 26;23:4117-4125. doi: 10.12659/msm.903245.
• Background Reis M, Czupalla CJ, Ziegler N, Devraj K, Zinke J, Seidel S, Heck R, Thom S, Macas J, Bockamp E, Fruttiger M, Taketo MM, Dimmeler S, Plate KH, Liebner S. Endothelial Wnt/beta-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression. J Exp Med. 2012 Aug 27;209(9):1611-27. doi: 10.1084/jem.20111580. Epub 2012 Aug 20.
• Background Zhang L, Xu L, Zhang F, Vlashi E. Doxycycline inhibits the cancer stem cell phenotype and epithelial-to-mesenchymal transition in breast cancer. Cell Cycle. 2017 Apr 18;16(8):737-745. doi: 10.1080/15384101.2016.1241929. Epub 2016 Oct 18.
• Background Sharon D, Cathelin S, Mirali S, Di Trani JM, Yanofsky DJ, Keon KA, Rubinstein JL, Schimmer AD, Ketela T, Chan SM. Inhibition of mitochondrial translation overcomes venetoclax resistance in AML through activation of the integrated stress response. Sci Transl Med. 2019 Oct 30;11(516):eaax2863. doi: 10.1126/scitranslmed.aax2863.
• Background Rok J, Karkoszka M, Rzepka Z, Respondek M, Banach K, Beberok A, Wrzesniok D. Cytotoxic and proapoptotic effect of doxycycline - An in vitro study on the human skin melanoma cells. Toxicol In Vitro. 2020 Jun;65:104790. doi: 10.1016/j.tiv.2020.104790. Epub 2020 Feb 8.
• Background Shen LC, Chen YK, Lin LM, Shaw SY. Anti-invasion and anti-tumor growth effect of doxycycline treatment for human oral squamous-cell carcinoma--in vitro and in vivo studies. Oral Oncol. 2010 Mar;46(3):178-84. doi: 10.1016/j.oraloncology.2009.11.013. Epub 2009 Dec 29.
• Background Hadjimichael AC, Foukas AF, Savvidou OD, Mavrogenis AF, Psyrri AK, Papagelopoulos PJ. The anti-neoplastic effect of doxycycline in osteosarcoma as a metalloproteinase (MMP) inhibitor: a systematic review. Clin Sarcoma Res. 2020 Apr 30;10:7. doi: 10.1186/s13569-020-00128-6. eCollection 2020.
• Background Lee MJ, Hung SH, Huang MC, Tsai T, Chen CT. Doxycycline potentiates antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy in malignant peripheral nerve sheath tumor cells. PLoS One. 2017 May 30;12(5):e0178493. doi: 10.1371/journal.pone.0178493. eCollection 2017.
• Background Ren Y, Hyakusoku H, Sagers JE, Landegger LD, Welling DB, Stankovic KM. MMP-14 (MT1-MMP) Is a Biomarker of Surgical Outcome and a Potential Mediator of Hearing Loss in Patients With Vestibular Schwannomas. Front Cell Neurosci. 2020 Jul 28;14:191. doi: 10.3389/fncel.2020.00191. eCollection 2020.
• Background Sagers JE, Sahin MI, Moon I, Ahmed SG, Stemmer-Rachamimov A, Brenner GJ, Stankovic KM. NLRP3 inflammasome activation in human vestibular schwannoma: Implications for tumor-induced hearing loss. Hear Res. 2019 Sep 15;381:107770. doi: 10.1016/j.heares.2019.07.007. Epub 2019 Jul 17.
• Background Thalheimer RD, Merker VL, Ly KI, Champlain A, Sawaya J, Askenazi NL, Herr HP, Da JLW, Jordan JT, Muzikansky A, Pearce EM, Sakamoto FH, Blakeley JO, Anderson RR, Plotkin SR; REiNS International Collaboration. Validating Techniques for Measurement of Cutaneous Neurofibromas: Recommendations for Clinical Trials. Neurology. 2021 Aug 17;97(7 Suppl 1):S32-S41. doi: 10.1212/WNL.0000000000012428. Epub 2021 Jul 6.

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