Scientific Posters

Randomized, Controlled, Multicenter, Multinational Phase II Study of Docetaxel (DCT) or AXL1717 Treatment in Patients with Squamous Cell Carcinoma (SCC) or Adenocarcinoma (AC) of Non-Small Cell Lung Cancer (NSCLC)."

Presented at the American Society of Clinical Oncology Annual Meeting, May/June 2014, Chicago, IL, USA.

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A Novel Targeted Oral Insulin-Like Growth Factor-1 Receptor (IGF-1R) Inhibitor and its Implications for Patients with Non-Small Cell Lung Cancer (NSCLC): A Phase I Clinical Trial.”  

Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, June 2012, Chicago, IL, USA.

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Scientific Publications

By Axelar’s founders and other researchers

Ekman S, Harmenberg J, Frödin JE, Bergström S, Wassberg C, Eksborg S, Larsson O, Axelson M, Jerling M, Abrahmsen L, Hedlund Å, Alvfors C, Ståhl B, Bergqvist M. A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma: A phase I clinical trial. Acta Oncol. 2015 Jul 10:1-9.

Holgersson G, Bergström S, Harmenberg J, Ringbom M, Klockare M, Jerling M, Ekman S, Lundström KL, Koyi H, Brandén E, Larsson O, Bergqvist M. A phase I pilot study of the insulin-like growth factor 1 receptor pathway modulator AXL1717 in combination with gemcitabine HCl and carboplatin in previously untreated, locally advanced, or metastatic non-small cell lung cancer. Med Oncol. 2015 Apr;32(4):129.

Bieghs L, Lub S, Fostier K, Maes K, Van Valckenborgh E, Menu E, Johnsen HE, Overgaard MT, Larsson O, Axelson M, Nyegaard M, Schots R, Jernberg-Wiklund H, Vanderkerken K, De Bruyne E. The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic. Oncotarget. 2014 Nov 30;5(22):11193-208.

Waraky A, Akopyan K, Parrow V, Strömberg T, Axelson M, Abrahmsén L, Lindqvist A, Larsson O, Aleem E. Picropodophyllin causes mitotic arrest and catastrophe by depolymerizing microtubules via insulin-like growth factor-1 receptor-independent mechanism. Oncotarget. 2014 Sep 30;5(18):8379-92.

Lemaire M, Fristedt C, Agarwal P, Menu E, Van Valckenborgh E, De Bruyne E, Österborg A, Atadja P, Larsson O, Axelson M, Van Camp B, Jernberg-Wiklund H, Vanderkerken K. The HDAC inhibitor LBH589 enhances the antimyeloma effects of the IGF-1RTK inhibitor picropodophyllin. Clin Cancer Res. 2012 Apr 15;18(8):2230-9.

Feng X, Aleem E, Lin Y, Axelson M, Larsson O, Strömberg T. Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: clinical implications. Int J Oncol. 2012 Apr;40(4):1251-8.

Doghman M, Axelson M, Lalli E. Potent inhibitory effect of the cyclolignan picropodophyllin (PPP) on human adrenocortical carcinoma cells proliferation. Am J Cancer Res. 2011;1(3):356-361.

Ekman, S., et al., Clinical Phase I study with an Insulin-like Growth Factor-1 Receptor Inhibitor: Experiences in patients with squamous non-small cell lung carcinoma. Acta oncologica 2011 Apr;50(3):441-7. Epub 2010 Aug 11.

Hashemi J, Worrall C, Vasilcanu D, Fryknäs M, Sulaiman L, Karimi M, Weng WH, Lui WO, Rudduck C, Axelson M, Jernberg-Wiklund H, Girnita L, Larsson O, Larsson C. Molecular characterization of acquired tolerance of tumor cells to picropodophyllin (PPP). PLoS One. 2011 Mar 14;6(3):e14757.

Rönquist-Nii Y, Eksborg S, Axelson M, Harmenberg J, Ekman S, Bergqvist M, Beck O. Determination of picropodophyllin and its isomer podophyllotoxin in human serum samples with electrospray ionization of hexylamine adducts by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Feb 15;879(5-6):326-34.

Yin S, Girnita A, Strömberg T, Khan Z, Andersson S, Zheng H, Ericsson C, Axelson M, Nistér M, Larsson O, Ekström TJ, Girnita L. Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma. Neuro Oncol. 2010 Jan;12(1):19-27.

Vasilcanu R, Vasilcanu D, Rosengren L, Natalishvili N, Sehat B, Yin S, Girnita A, Axelson M, Girnita L, Larsson O. Picropodophyllin induces downregulation of the insulin-like growth factor 1 receptor: potential mechanistic involvement of Mdm2 and ß-arrestin1. Oncogene 2008 6;27(11),1629-1638. (Epub: 10 Sept 2007).

Menu E, Jernberg-Wiklund H, De Raeve H, De Leenheer E, Coulton L, Gallagher O, Van Valckenborgh E, Larsson O, Axelson M, Nilsson K, Van Camp B, Croucher P, Vanderkerken K. Targeting the IGF-1R using picropodophyllin in the therapeutical 5T2 MM mouse of multiple myeloma: Beneficial effects on tumor growth, angiogenesis, bone disease and survival. Int J Cancer 2007 Oct 15;121(8):1857-61.

Girnita A, All-Ericsson C, Economou M, Åström K, Axelson M, Seregard S, Larsson O, Girnita L. The insulin-like growth factor-1 receptor (IGF-1R) inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of uveal melanoma cells. Clin Cancer Res, 2006 12(4), 1383-1391.

Menu E, Jernberg-Wiklund H, Stromberg T, De Raeve H, Girnita L, Larsson O, Axelson M, Asosingh K, Nilsson K, Van Camp B and Vanderkerken K. Effects of inhibition of the IGF-1 receptor tyrosine kinase in multiple myeloma: an in vitro and in vivo study on the 5T33MM Mouse Model. Blood 2006 Jan 15;107(2):655-60.

Girnita A, Girnita L, d. Prete F, Bartolazzi A, Larsson O, Axelson M. Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth. Cancer Research, 64, 236-242, 2004.

By independent research groups

Zhang Q, Pan J, Lubet RA, Wang Y, You M. Targeting the insulin-like growth factor-1 receptor by picropodophyllin for lung cancer chemoprevention. Mol Carcinog. 2015 Jun;54 Suppl 1:E129-37.

Tworkoski K, Raab-Traub N. LMP1 promotes expression of insulin-like growth factor 1 (IGF1) to selectively activate IGF1 receptor and drive cell proliferation. J Virol. 2015 Mar;89(5):2590-602.

Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Sueishi M. Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells. Oncol Lett. 2014 Nov;8(5):2023-2026.

Singh RK, Gaikwad SM, Jinager A, Chaudhury S, Maheshwari A, Ray P. IGF-1R inhibition potentiates cytotoxic effects of chemotherapeutic agents in early stages of chemoresistant ovarian cancer cells. Cancer Lett. 2014 Nov 28;354(2):254-62.

Benabbou N, Mirshahi P, Bordu C, Faussat AM, Tang R, Therwath A, Soria J, Marie JP, Mirshahi M. A subset of bone marrow stromal cells regulate ATP-binding cassette gene expression via insulin-like growth factor-I in a leukemia cell line. Int J Oncol. 2014 Oct;45(4):1372-80. doi: 10.3892/ijo.2014.2569.

Huang Z, Fang Z, Zhen H, Zhou L, Amin HM, Shi P. Inhibition of type I insulin-like growth factor receptor tyrosine kinase by picropodophyllin induces apoptosis and cell cycle arrest in T lymphoblastic leukemia/lymphoma. Leuk Lymphoma. 2014 Aug;55(8):1876-83.

E C, Li J, Shao D, Zhang D, Pan Y, Chen L, Zhang X. The insulin-like growth factor-I receptor inhibitor picropodophyllin-induced selective apoptosis of hepatocellular carcinoma cell through a caspase-dependent mitochondrial pathway. Oncol Res. 2013;21(2):103-10

Dong Z, Yao M, Wang L, Yan X, Gu X, Shi Y, Yao N, Qiu L, Wu W, Yao D. Abnormal expression of insulin-like growth factor-I receptor in hepatoma tissue and its inhibition to promote apoptosis of tumor cells. Tumour Biol. 2013 Dec;34(6):3397-405.

Wang Q, Wei F, Lv G, Li C, Liu T, Hadjipanayis CG, Zhang G, Hao C, Bellail AC. The association of TP53 mutations with the resistance of colorectal carcinoma to the insulin-like growth factor-1 receptor inhibitor picropodophyllin. BMC Cancer. 2013 Nov 4;13:521.

Saldana SM, Lee HH, Lowery FJ, Khotskaya YB, Xia W, Zhang C, Chang SS, Chou CK, Steeg PS, Yu D, Hung MC. Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis. PLoS One. 2013 Sep 5;8(9):e73406.

Yin SC, Guo W, Tao ZZ. Picropodophyllin inhibits tumor growth of human nasopharyngeal carcinoma in a mouse model. Biochem Biophys Res Commun. 2013 Sep 13;439(1):1-5.

Wu X, Sooman L, Wickström M, Fryknäs M, Dyrager C, Lennartsson J, Gullbo J. Alternative cytotoxic effects of the postulated IGF-IR inhibitor picropodophyllin in vitro. Mol Cancer Ther. 2013 Aug;12(8):1526-36.

Lu X, Wang L, Mei J, Wang X, Zhu X, Zhang Q, Lv J. Picropodophyllin inhibits epithelial ovarian cancer cells in vitro and in vivo. Biochem Biophys Res Commun. 2013 Jun 7;435(3):385-90.

Chang WW, Lin RJ, Yu J, Chang WY, Fu CH, Lai A, Yu JC, Yu AL. The expression and significance of insulin-like growth factor-1 receptor and its pathway on breast cancer stem/progenitors. Breast Cancer Res. 2013 May 12;15(3):R39.

Pollak M. The insulin receptor/insulin-like growth factor receptor family as a therapeutic target in oncology. Clin Cancer Res. 2012 Jan 1;18(1):40-50.

Ozkan EE. Plasma and tissue insulin-like growth factor-I receptor (IGF-IR) as a prognostic marker for prostate cancer and anti-IGF-IR agents as novel therapeutic strategy for refractory cases: a review. Mol Cell Endocrinol. 2011 Sep 15;344(1-2):1-24.

Vishwamitra D, Shi P, Wilson D, Manshouri R, Vega F, Schlette EJ, Amin HM. Expression and effects of inhibition of type I insulin-like growth factor receptor tyrosine kinase in mantle cell lymphoma. Haematologica. 2011 Jun;96(6):871-80.

Ray S, Darbre PD. Crosstalk with insulin and dependence on PI3K/Akt/mTOR rather than MAPK pathways in upregulation of basal growth following long-term oestrogen deprivation in three human breast cancer cell lines. Horm Mol Biol Clin Investig. 2011 Mar 1;5(2):53-65.

Ohshima-Hosoyama S, Hosoyama T, Nelon LD, Keller C. IGF-1 receptor inhibition by picropodophyllin in medulloblastoma. Biochem Biophys Res Commun. 2010 Sep 3;399(4):727-32.

Karasic TB, Hei TK, Ivanov VN. Disruption of IGF-1R signaling increases TRAIL-induced apoptosis: a new potential therapy for the treatment of melanoma. Exp Cell Res. 2010 Jul 15;316(12):1994-2007.

Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T. Insulin-like growth factor-I receptor in proliferation and motility of pancreatic cancer. World J Gastroenterol. 2010 Apr 21;16(15):1854-8.

Duan Z, Choy E, Harmon D, Yang C, Ryu K, Schwab J, Mankin H, Hornicek FJ. Insulin-like growth factor-I receptor tyrosine kinase inhibitor cyclolignan picropodophyllin inhibits proliferation and induces apoptosis in multidrug resistant osteosarcoma cell lines. Mol Cancer Ther. 2009 Aug;8(8):2122-30.

Klinakis A, Szabolcs M, Chen G, Xuan S, Hibshoosh H, Efstratiadis A. Igf1r as a therapeutic target in a mouse model of basal-like breast cancer. Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2359-64.

Hewish M, Chau I, Cunningham D. Insulin-like growth factor 1 receptor targeted therapeutics: novel compounds and novel treatment strategies for cancer medicine. Recent Pat Anticancer Drug Discov. 2009 Jan;4(1):54-72.

Gualberto, A. and M. Pollak, Clinical development of inhibitors of the insulin-like growth factor receptor in oncology. Curr Drug Targets, 2009. 10(10): p. 923-36.

Klinakis, A., et al., Igf1r as a therapeutic target in a mouse model of basal-like breast cancer. Proc Natl Acad Sci U S A, 2009. 106(7): p. 2359-64.

Pollak, M., Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer, 2008. 8(12): p. 915-28.

Clemmons, D.R., Modifying IGF1 activity: An approach to treat endocrine disorders, atherosclerosis and cancer. Nat Rev Drug Discov, 2007 6(10): p. 821-33.

Zhu L, Pollard JW. Estradiol-17ß regulates mouse uterine epithelial cell proliferation through insulin-like growth factor 1 signaling. Proc Natl Acad Sci (USA). October 2, 2007 vol. 104: 15847–15851.

Fulzele K, Digirolamo DJ, Liu Z, Xu J, Messina JL, Clemens TL. Disruption of the insulin-like growth factor type 1 receptor in osteoblasts enhances insulin signaling and action. J Biol Chem. 2007 Aug 31;282(35):25649-58. Epub 2007 Jun 6.

Guha M, Srinivasan S, Biswas G, Avadhani NG. Activation of a novel calcineurin-mediated insulin-like growth factor-1 receptor pathway, altered metabolism, and tumor cell invasion in cells subjected to mitochondrial respiratory stress. J Biol Chem. 2007 May 11;282(19):14536-46.

Conti L, Regis G, Longo A, Bernabei P, Chiarle R, Giovarelli M, Novelli F. In the absence of IGF-1 signaling, IFN-gamma suppresses human malignant T-cell growth. Blood. 2007 Mar 15;109(6): 2496-2504.