Skip to main content
Erschienen in: Current Treatment Options in Oncology 1/2020

01.01.2020 | Leukemia (PH Wiernik, Section Editor)

Current and Future Molecular Targets for Acute Myeloid Leukemia Therapy

verfasst von: Shaheedul A. Sami, PharmD, Noureldien H. E. Darwish, MD PhD, Amanda N. M. Barile, PharmD, Shaker A. Mousa, PhD

Erschienen in: Current Treatment Options in Oncology | Ausgabe 1/2020

Einloggen, um Zugang zu erhalten

Opinion statement

Acute myeloid leukemia (AML) disease prognosis is poor and there is a high risk of chemo-resistant relapse for both young and old patients. Thus, there is a demand for alternative and target-specific drugs to improve the 5-year survival rate. Current treatment mainstays include chemotherapy, or mutation-specific targeting molecules including FLT3 inhibitors, IDH inhibitors, and monoclonal antibodies. Efforts to devise new, targeted therapy have included recent advances in methods for high-throughput genomic screening and the availability of computer-assisted techniques for the design of novel agents predicted to specifically inhibit mutant molecules involved in leukemogenesis. Crosstalk between the leukemia cells and the bone marrow microenvironment through cell surface molecules, such as the integrins αvβ3 and αvβ5, might influence drug response and AML progression. This review article focuses on current AML treatment options, new AML targeted therapies, the role of integrins in AML progression, and a potential therapeutic agent—integrin αvβ3 antagonist.
Literatur
1.
Zurück zum Zitat Greenberg PL, Gordeuk V, Issaragrisil S, Siritanaratkul N, Fucharoen S, Ribeiro RC. Major hematologic diseases in the developing world—new aspects of diagnosis and management of thalassemia, malarial anemia, and acute leukemia. Hematology Am Soc Hematol Educ Program. 2001:479–98. Greenberg PL, Gordeuk V, Issaragrisil S, Siritanaratkul N, Fucharoen S, Ribeiro RC. Major hematologic diseases in the developing world—new aspects of diagnosis and management of thalassemia, malarial anemia, and acute leukemia. Hematology Am Soc Hematol Educ Program. 2001:479–98.
2.
Zurück zum Zitat Gocek E, Marcinkowska E. Differentiation therapy of acute myeloid leukemia. Cancers (Basel). 2011;3:2402–20.CrossRef Gocek E, Marcinkowska E. Differentiation therapy of acute myeloid leukemia. Cancers (Basel). 2011;3:2402–20.CrossRef
4.
Zurück zum Zitat Deschler B, Lubbert M. Acute myeloid leukemia: epidemiology and etiology. Cancer. 2006;107:2099–107.PubMedCrossRef Deschler B, Lubbert M. Acute myeloid leukemia: epidemiology and etiology. Cancer. 2006;107:2099–107.PubMedCrossRef
6.
Zurück zum Zitat Bayat Mokhtari R, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, et al. Combination therapy in combating cancer. Oncotarget. 2017;8:38022–43.PubMedCrossRef Bayat Mokhtari R, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, et al. Combination therapy in combating cancer. Oncotarget. 2017;8:38022–43.PubMedCrossRef
7.
Zurück zum Zitat Johansen S, Brenner AK, Bartaula-Brevik S, Reikvam H, Bruserud Ø. The possible importance of β3 integrins for leukemogenesis and chemoresistance in acute myeloid leukemia. Int J Mol Sci. 2018;19:251.PubMedCentralCrossRef Johansen S, Brenner AK, Bartaula-Brevik S, Reikvam H, Bruserud Ø. The possible importance of β3 integrins for leukemogenesis and chemoresistance in acute myeloid leukemia. Int J Mol Sci. 2018;19:251.PubMedCentralCrossRef
8.
Zurück zum Zitat Raab-Westphal S, Marshall JF, Goodman SL. Integrins as therapeutic targets: successes and cancers. Cancers (Basel). 2017;9:110.CrossRef Raab-Westphal S, Marshall JF, Goodman SL. Integrins as therapeutic targets: successes and cancers. Cancers (Basel). 2017;9:110.CrossRef
9.
Zurück zum Zitat Licht JD, Sternberg DW. The molecular pathology of acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2005:137–42.CrossRef Licht JD, Sternberg DW. The molecular pathology of acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2005:137–42.CrossRef
11.
Zurück zum Zitat Lagunas-Rangel FA, Chávez-Valencia V, Gómez-Guijosa MÁ, Cortes-Penagos C. Acute myeloid leukemia—genetic alterations and their clinical prognosis. Int J Hematol Oncol Stem Cell Res. 2017;11:328–39.PubMedPubMedCentral Lagunas-Rangel FA, Chávez-Valencia V, Gómez-Guijosa MÁ, Cortes-Penagos C. Acute myeloid leukemia—genetic alterations and their clinical prognosis. Int J Hematol Oncol Stem Cell Res. 2017;11:328–39.PubMedPubMedCentral
12.
14.
Zurück zum Zitat Montero J, Letai A. Why do BCL-2 inhibitors work and where should we use them in the clinic? Cell Death Differ. 2018;25:56–64.PubMedCrossRef Montero J, Letai A. Why do BCL-2 inhibitors work and where should we use them in the clinic? Cell Death Differ. 2018;25:56–64.PubMedCrossRef
15.
16.
Zurück zum Zitat Oren M, Rotter V. Mutant p53 gain-of-function in cancer. Cold Spring Harb Perspect Biol. 2010;2:a001107-a.CrossRef Oren M, Rotter V. Mutant p53 gain-of-function in cancer. Cold Spring Harb Perspect Biol. 2010;2:a001107-a.CrossRef
17.
Zurück zum Zitat Kindle KB, Troke PJ, Collins HM, Matsuda S, Bossi D, Bellodi C, et al. MOZ-TIF2 inhibits transcription by nuclear receptors and p53 by impairment of CBP function. Mol Cell Biol. 2005;25:988–1002.PubMedPubMedCentralCrossRef Kindle KB, Troke PJ, Collins HM, Matsuda S, Bossi D, Bellodi C, et al. MOZ-TIF2 inhibits transcription by nuclear receptors and p53 by impairment of CBP function. Mol Cell Biol. 2005;25:988–1002.PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352:254–66.PubMedCrossRef Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352:254–66.PubMedCrossRef
19.
Zurück zum Zitat Liu S, Shen T, Huynh L, Klisovic MI, Rush LJ, Ford JL, et al. Interplay of RUNX1/MTG8 and DNA methyltransferase 1 in acute myeloid leukemia. Cancer Res. 2005;65:1277–84.PubMedCrossRef Liu S, Shen T, Huynh L, Klisovic MI, Rush LJ, Ford JL, et al. Interplay of RUNX1/MTG8 and DNA methyltransferase 1 in acute myeloid leukemia. Cancer Res. 2005;65:1277–84.PubMedCrossRef
20.
Zurück zum Zitat Stucki A, Rivier AS, Gikic M, Monai N, Schapira M, Spertini O. Endothelial cell activation by myeloblasts: molecular mechanisms of leukostasis and leukemic cell dissemination. Blood. 2001;97:2121–9.PubMedCrossRef Stucki A, Rivier AS, Gikic M, Monai N, Schapira M, Spertini O. Endothelial cell activation by myeloblasts: molecular mechanisms of leukostasis and leukemic cell dissemination. Blood. 2001;97:2121–9.PubMedCrossRef
22.
Zurück zum Zitat Guo W, Giancotti FG. Integrin signaling during tumor progression. Nat Rev Mol Cell Biol. 2004;5:816–26.PubMedCrossRef Guo W, Giancotti FG. Integrin signaling during tumor progression. Nat Rev Mol Cell Biol. 2004;5:816–26.PubMedCrossRef
23.
Zurück zum Zitat Song X, Wei Z, Shaikh ZA. Requirement of ERα and basal activities of EGFR and Src kinase in Cd-induced activation of MAPK/ERK pathway in human breast cancer MCF-7 cells. Toxicol Appl Pharmacol. 2015;287:26–34.PubMedPubMedCentralCrossRef Song X, Wei Z, Shaikh ZA. Requirement of ERα and basal activities of EGFR and Src kinase in Cd-induced activation of MAPK/ERK pathway in human breast cancer MCF-7 cells. Toxicol Appl Pharmacol. 2015;287:26–34.PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Saif A, Kazmi SFA, Naseem R, Shah H, Butt MO. Acute myeloid leukemia: is that all there is? Cureus. 2018;10:e3198.PubMedPubMedCentral Saif A, Kazmi SFA, Naseem R, Shah H, Butt MO. Acute myeloid leukemia: is that all there is? Cureus. 2018;10:e3198.PubMedPubMedCentral
27.
Zurück zum Zitat O’Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, et al. Acute myeloid leukemia, version 3.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2017;15:926–57.CrossRef O’Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, et al. Acute myeloid leukemia, version 3.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2017;15:926–57.CrossRef
28.
Zurück zum Zitat Medinger M, Lengerke C, Passweg J. Novel prognostic and therapeutic mutations in acute myeloid leukemia. Cancer Genomics Proteomics. 2016;13:317–29.PubMedPubMedCentral Medinger M, Lengerke C, Passweg J. Novel prognostic and therapeutic mutations in acute myeloid leukemia. Cancer Genomics Proteomics. 2016;13:317–29.PubMedPubMedCentral
31.
Zurück zum Zitat Maurillo L, Buccisano F, Del Principe MI, Sarlo C, Di Caprio L, Ditto C, et al. Treatment of acute myeloid leukemia with 20–30% bone marrow blasts. Mediterr J Hematol Infect Dis. 2013;5:e2013032-e.CrossRef Maurillo L, Buccisano F, Del Principe MI, Sarlo C, Di Caprio L, Ditto C, et al. Treatment of acute myeloid leukemia with 20–30% bone marrow blasts. Mediterr J Hematol Infect Dis. 2013;5:e2013032-e.CrossRef
34.
Zurück zum Zitat • Lee LY, Hernandez D, Rajkhowa T, Smith SC, Raman JR, Nguyen B, et al. Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor. Blood. 2017;129:257–60 The inhibitory activity of gilteritinib against different forms of FLT3 mutations in leukemia cells was studied with immunoblotting. Gilteritinib showed significant inhibitor activity against different FLT3 mutations including the resistant mutations.PubMedPubMedCentralCrossRef • Lee LY, Hernandez D, Rajkhowa T, Smith SC, Raman JR, Nguyen B, et al. Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor. Blood. 2017;129:257–60 The inhibitory activity of gilteritinib against different forms of FLT3 mutations in leukemia cells was studied with immunoblotting. Gilteritinib showed significant inhibitor activity against different FLT3 mutations including the resistant mutations.PubMedPubMedCentralCrossRef
35.
Zurück zum Zitat Liu T, Ivaturi V, Sabato P, Gobburu JV, Greer JM, Wright JJ, et al. Sorafenib dose recommendation in acute myeloid leukemia based on exposure-FLT3 relationship. Clin Transl Sci. 2018;11:435–43.PubMedPubMedCentralCrossRef Liu T, Ivaturi V, Sabato P, Gobburu JV, Greer JM, Wright JJ, et al. Sorafenib dose recommendation in acute myeloid leukemia based on exposure-FLT3 relationship. Clin Transl Sci. 2018;11:435–43.PubMedPubMedCentralCrossRef
36.
Zurück zum Zitat Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003;9:327–37.PubMed Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003;9:327–37.PubMed
37.
Zurück zum Zitat Levis M, Allebach J, Tse K-F, Zheng R, Baldwin BR, Smith BD, et al. A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood. 2002;99:3885–91.PubMedCrossRef Levis M, Allebach J, Tse K-F, Zheng R, Baldwin BR, Smith BD, et al. A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood. 2002;99:3885–91.PubMedCrossRef
40.
Zurück zum Zitat Kampa-Schittenhelm KM, Heinrich MC, Akmut F, Dohner H, Dohner K, Schittenhelm MM. Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms. Mol Cancer. 2013;12:19.PubMedPubMedCentralCrossRef Kampa-Schittenhelm KM, Heinrich MC, Akmut F, Dohner H, Dohner K, Schittenhelm MM. Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms. Mol Cancer. 2013;12:19.PubMedPubMedCentralCrossRef
41.
Zurück zum Zitat Kampa-Schittenhelm KM, Frey J, Haeusser LA, Illing B, Pavlovsky AA, Blumenstock G, et al. Crenolanib is a type I tyrosine kinase inhibitor that inhibits mutant KIT D816 isoforms prevalent in systemic mastocytosis and core binding factor leukemia. Oncotarget. 2017;8:82897–909.PubMedPubMedCentralCrossRef Kampa-Schittenhelm KM, Frey J, Haeusser LA, Illing B, Pavlovsky AA, Blumenstock G, et al. Crenolanib is a type I tyrosine kinase inhibitor that inhibits mutant KIT D816 isoforms prevalent in systemic mastocytosis and core binding factor leukemia. Oncotarget. 2017;8:82897–909.PubMedPubMedCentralCrossRef
42.
Zurück zum Zitat Mathew NR, Baumgartner F, Braun L, O’Sullivan D, Thomas S, Waterhouse M, et al. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med. 2018;24:282.PubMedPubMedCentralCrossRef Mathew NR, Baumgartner F, Braun L, O’Sullivan D, Thomas S, Waterhouse M, et al. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med. 2018;24:282.PubMedPubMedCentralCrossRef
43.
Zurück zum Zitat Lange A, Jaskula E, Lange J, Dworacki G, Nowak D, Simiczyjew A, et al. The sorafenib anti-relapse effect after alloHSCT is associated with heightened alloreactivity and accumulation of CD8+ PD-1+(CD279+) lymphocytes in marrow. PLoS One. 2018;13:e0190525.PubMedPubMedCentralCrossRef Lange A, Jaskula E, Lange J, Dworacki G, Nowak D, Simiczyjew A, et al. The sorafenib anti-relapse effect after alloHSCT is associated with heightened alloreactivity and accumulation of CD8+ PD-1+(CD279+) lymphocytes in marrow. PLoS One. 2018;13:e0190525.PubMedPubMedCentralCrossRef
44.
Zurück zum Zitat Zhao W, Zhang T, Qu B, Wu X, Zhu X, Meng F, et al. Sorafenib induces apoptosis in HL60 cells by inhibiting Src kinase-mediated STAT3 phosphorylation. Anti-Cancer Drugs. 2011;22:79–88.PubMedCrossRef Zhao W, Zhang T, Qu B, Wu X, Zhu X, Meng F, et al. Sorafenib induces apoptosis in HL60 cells by inhibiting Src kinase-mediated STAT3 phosphorylation. Anti-Cancer Drugs. 2011;22:79–88.PubMedCrossRef
45.
Zurück zum Zitat Feldmann F, Schenk B, Martens S, Vandenabeele P, Fulda S. Sorafenib inhibits therapeutic induction of necroptosis in acute leukemia cells. Oncotarget. 2017;8:68208.PubMedPubMedCentralCrossRef Feldmann F, Schenk B, Martens S, Vandenabeele P, Fulda S. Sorafenib inhibits therapeutic induction of necroptosis in acute leukemia cells. Oncotarget. 2017;8:68208.PubMedPubMedCentralCrossRef
46.
Zurück zum Zitat Wander SA, Levis MJ, Fathi AT. The evolving role of FLT3 inhibitors in acute myeloid leukemia: quizartinib and beyond. Ther Adv Hematol. 2014;5:65–77.PubMedPubMedCentralCrossRef Wander SA, Levis MJ, Fathi AT. The evolving role of FLT3 inhibitors in acute myeloid leukemia: quizartinib and beyond. Ther Adv Hematol. 2014;5:65–77.PubMedPubMedCentralCrossRef
47.
Zurück zum Zitat DiNardo CD, Stone RM, Medeiros BC. Novel therapeutics in acute myeloid leukemia. Am Soc Clin Oncol Educ Book. 2017;37:495–503.PubMedCrossRef DiNardo CD, Stone RM, Medeiros BC. Novel therapeutics in acute myeloid leukemia. Am Soc Clin Oncol Educ Book. 2017;37:495–503.PubMedCrossRef
49.
Zurück zum Zitat Demaria M, O’Leary MN, Chang J, Shao L, Liu S, Alimirah F, et al. Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov. 2017;7:165–76.PubMedCrossRef Demaria M, O’Leary MN, Chang J, Shao L, Liu S, Alimirah F, et al. Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov. 2017;7:165–76.PubMedCrossRef
51.
Zurück zum Zitat Cucchi DG, Denys B, Kaspers GJ, Janssen JJ, Ossenkoppele GJ, de Haas V, et al. RNA-based FLT3-ITD allelic ratio is associated with outcome and ex vivo response to FLT3 inhibitors in pediatric AML. Blood. 2018;131:2485–9.PubMedCrossRef Cucchi DG, Denys B, Kaspers GJ, Janssen JJ, Ossenkoppele GJ, de Haas V, et al. RNA-based FLT3-ITD allelic ratio is associated with outcome and ex vivo response to FLT3 inhibitors in pediatric AML. Blood. 2018;131:2485–9.PubMedCrossRef
52.
Zurück zum Zitat Mori M, Kaneko N, Ueno Y, Yamada M, Tanaka R, Saito R, et al. Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia. Investig New Drugs. 2017;35:556–65.CrossRef Mori M, Kaneko N, Ueno Y, Yamada M, Tanaka R, Saito R, et al. Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia. Investig New Drugs. 2017;35:556–65.CrossRef
53.
Zurück zum Zitat Short NJ, Kantarjian H, Ravandi F, Daver N. Emerging treatment paradigms with FLT3 inhibitors in acute myeloid leukemia. Ther Adv Hematol. 2019;10:2040620719827310.PubMedPubMedCentralCrossRef Short NJ, Kantarjian H, Ravandi F, Daver N. Emerging treatment paradigms with FLT3 inhibitors in acute myeloid leukemia. Ther Adv Hematol. 2019;10:2040620719827310.PubMedPubMedCentralCrossRef
54.
Zurück zum Zitat Stone RM. Which new agents will be incorporated into frontline therapy in acute myeloid leukemia? Best Pract Res Clin Haematol. 2017;30:312–6.PubMedCrossRef Stone RM. Which new agents will be incorporated into frontline therapy in acute myeloid leukemia? Best Pract Res Clin Haematol. 2017;30:312–6.PubMedCrossRef
55.
Zurück zum Zitat Myers RA, Wirth S, Williams S, Kiel PJ. Enasidenib: An oral IDH2 inhibitor for the treatment of acute myeloid leukemia. J Adv Pract Oncol. 2018;9:435–40.PubMedPubMedCentral Myers RA, Wirth S, Williams S, Kiel PJ. Enasidenib: An oral IDH2 inhibitor for the treatment of acute myeloid leukemia. J Adv Pract Oncol. 2018;9:435–40.PubMedPubMedCentral
56.
58.
Zurück zum Zitat Willems E, Dedobbeleer M, Digregorio M, Lombard A, Lumapat PN, Rogister B. The functional diversity of Aurora kinases: a comprehensive review. Cell Div. 2018;13:7. Willems E, Dedobbeleer M, Digregorio M, Lombard A, Lumapat PN, Rogister B. The functional diversity of Aurora kinases: a comprehensive review. Cell Div. 2018;13:7.
59.
Zurück zum Zitat Kim S-J, Jang JE, Cheong J-W, Eom J-I, Jeung H-K, Kim Y, et al. Aurora A kinase expression is increased in leukemia stem cells, and a selective Aurora A kinase inhibitor enhances Ara-C-induced apoptosis in acute myeloid leukemia stem cells. Korean J Hematol. 2012;47:178–85.PubMedPubMedCentralCrossRef Kim S-J, Jang JE, Cheong J-W, Eom J-I, Jeung H-K, Kim Y, et al. Aurora A kinase expression is increased in leukemia stem cells, and a selective Aurora A kinase inhibitor enhances Ara-C-induced apoptosis in acute myeloid leukemia stem cells. Korean J Hematol. 2012;47:178–85.PubMedPubMedCentralCrossRef
60.
Zurück zum Zitat Yang Y, Shen Y, Li S, Jin N, Liu H, Yao X. Molecular dynamics and free energy studies on Aurora kinase A and its mutant bound with MLN8054: insight into molecular mechanism of subtype selectivity. Mol BioSyst. 2012;8:3049–60.PubMedCrossRef Yang Y, Shen Y, Li S, Jin N, Liu H, Yao X. Molecular dynamics and free energy studies on Aurora kinase A and its mutant bound with MLN8054: insight into molecular mechanism of subtype selectivity. Mol BioSyst. 2012;8:3049–60.PubMedCrossRef
61.
Zurück zum Zitat Wang X, Sinn AL, Pollok K, Sandusky G, Zhang S, Chen L, et al. Preclinical activity of a novel multiple tyrosine kinase and aurora kinase inhibitor, ENMD-2076, against multiple myeloma. Br J Haematol. 2010;150:313–25.PubMedCrossRef Wang X, Sinn AL, Pollok K, Sandusky G, Zhang S, Chen L, et al. Preclinical activity of a novel multiple tyrosine kinase and aurora kinase inhibitor, ENMD-2076, against multiple myeloma. Br J Haematol. 2010;150:313–25.PubMedCrossRef
62.
Zurück zum Zitat Melichar B, Adenis A, Lockhart AC, Bennouna J, Dees EC, Kayaleh O, et al. Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. Lancet Oncol. 2015;16:395–405.PubMedCrossRef Melichar B, Adenis A, Lockhart AC, Bennouna J, Dees EC, Kayaleh O, et al. Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. Lancet Oncol. 2015;16:395–405.PubMedCrossRef
63.
Zurück zum Zitat Barr PM, Li H, Spier C, Mahadevan D, LeBlanc M, Ul Haq M, et al. Phase II intergroup trial of alisertib in relapsed and refractory peripheral T cell lymphoma and transformed mycosis fungoides: SWOG 1108. J Clin Oncol. 2015;33:2399–404.PubMedPubMedCentralCrossRef Barr PM, Li H, Spier C, Mahadevan D, LeBlanc M, Ul Haq M, et al. Phase II intergroup trial of alisertib in relapsed and refractory peripheral T cell lymphoma and transformed mycosis fungoides: SWOG 1108. J Clin Oncol. 2015;33:2399–404.PubMedPubMedCentralCrossRef
64.
Zurück zum Zitat Lowenberg B, Muus P, Ossenkoppele G, Rousselot P, Cahn JY, Ifrah N, et al. Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia. Blood. 2011;118:6030–6.PubMedPubMedCentralCrossRef Lowenberg B, Muus P, Ossenkoppele G, Rousselot P, Cahn JY, Ifrah N, et al. Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia. Blood. 2011;118:6030–6.PubMedPubMedCentralCrossRef
65.
Zurück zum Zitat Kantarjian HM, Martinelli G, Jabbour EJ, Quintas-Cardama A, Ando K, Bay JO, et al. Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZD1152) versus low-dose cytosine arabinoside in elderly patients with acute myeloid leukemia. Cancer. 2013;119:2611–9.PubMedCrossRef Kantarjian HM, Martinelli G, Jabbour EJ, Quintas-Cardama A, Ando K, Bay JO, et al. Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZD1152) versus low-dose cytosine arabinoside in elderly patients with acute myeloid leukemia. Cancer. 2013;119:2611–9.PubMedCrossRef
66.
Zurück zum Zitat Soncini C, Carpinelli P, Gianellini L, Fancelli D, Vianello P, Rusconi L, et al. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006;12:4080–9.PubMedCrossRef Soncini C, Carpinelli P, Gianellini L, Fancelli D, Vianello P, Rusconi L, et al. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006;12:4080–9.PubMedCrossRef
70.
Zurück zum Zitat Park MH, Hong JT. Roles of NF-κB in cancer and inflammatory diseases and their therapeutic approaches. Cells. 2016;5:15.PubMedCentralCrossRef Park MH, Hong JT. Roles of NF-κB in cancer and inflammatory diseases and their therapeutic approaches. Cells. 2016;5:15.PubMedCentralCrossRef
71.
Zurück zum Zitat Annaloro C, Onida F, Saporiti G, Lambertenghi DG. Cancer stem cells in hematological disorders: current and possible new therapeutic approaches. Curr Pharm Biotechnol. 2011;12:217–25.PubMedCrossRef Annaloro C, Onida F, Saporiti G, Lambertenghi DG. Cancer stem cells in hematological disorders: current and possible new therapeutic approaches. Curr Pharm Biotechnol. 2011;12:217–25.PubMedCrossRef
72.
Zurück zum Zitat Shahshahan MA, Beckley MN, Jazirehi AR. Potential usage of proteasome inhibitor bortezomib (Velcade, PS-341) in the treatment of metastatic melanoma: basic and clinical aspects. Am J Cancer Res. 2011;1:913–24.PubMedPubMedCentral Shahshahan MA, Beckley MN, Jazirehi AR. Potential usage of proteasome inhibitor bortezomib (Velcade, PS-341) in the treatment of metastatic melanoma: basic and clinical aspects. Am J Cancer Res. 2011;1:913–24.PubMedPubMedCentral
73.
Zurück zum Zitat Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, et al. The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood. 2005;105:4163–9.PubMedPubMedCentralCrossRef Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, et al. The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood. 2005;105:4163–9.PubMedPubMedCentralCrossRef
74.
Zurück zum Zitat Ji Q, Ding Y-H, Sun Y, Zhang Y, Gao H-E, Song H-N, et al. Antineoplastic effects and mechanisms of micheliolide in acute myelogenous leukemia stem cells. Oncotarget. 2016;7:65012–23.PubMedPubMedCentralCrossRef Ji Q, Ding Y-H, Sun Y, Zhang Y, Gao H-E, Song H-N, et al. Antineoplastic effects and mechanisms of micheliolide in acute myelogenous leukemia stem cells. Oncotarget. 2016;7:65012–23.PubMedPubMedCentralCrossRef
75.
Zurück zum Zitat Darwish NH, Sudha T, Godugu K, Elbaz O, Abdelghaffar HA, Hassan EE, et al. Acute myeloid leukemia stem cell markers in prognosis and targeted therapy: potential impact of BMI-1, TIM-3 and CLL-1. Oncotarget. 2016;7:57811–20.PubMedPubMedCentralCrossRef Darwish NH, Sudha T, Godugu K, Elbaz O, Abdelghaffar HA, Hassan EE, et al. Acute myeloid leukemia stem cell markers in prognosis and targeted therapy: potential impact of BMI-1, TIM-3 and CLL-1. Oncotarget. 2016;7:57811–20.PubMedPubMedCentralCrossRef
76.
Zurück zum Zitat van Kemenade FJ, Raaphorst FM, Blokzijl T, Fieret E, Hamer KM, Satijn DP, et al. Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B cell non-Hodgkin lymphoma. Blood. 2001;97:3896–901.PubMedCrossRef van Kemenade FJ, Raaphorst FM, Blokzijl T, Fieret E, Hamer KM, Satijn DP, et al. Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B cell non-Hodgkin lymphoma. Blood. 2001;97:3896–901.PubMedCrossRef
77.
Zurück zum Zitat Mihara K, Chowdhury M, Nakaju N, Hidani S, Ihara A, Hyodo H, et al. Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and patient prognosis. Blood. 2006;107:305–8.PubMedCrossRef Mihara K, Chowdhury M, Nakaju N, Hidani S, Ihara A, Hyodo H, et al. Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and patient prognosis. Blood. 2006;107:305–8.PubMedCrossRef
78.
Zurück zum Zitat Iwama A, Oguro H, Negishi M, Kato Y, Morita Y, Tsukui H, et al. Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity. 2004;21:843–51.PubMedCrossRef Iwama A, Oguro H, Negishi M, Kato Y, Morita Y, Tsukui H, et al. Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity. 2004;21:843–51.PubMedCrossRef
79.
Zurück zum Zitat Kreso A, van Galen P, Pedley NM, Lima-Fernandes E, Frelin C, Davis T, et al. Self-renewal as a therapeutic target in human colorectal cancer. Nat Med. 2014;20:29–36.PubMedCrossRef Kreso A, van Galen P, Pedley NM, Lima-Fernandes E, Frelin C, Davis T, et al. Self-renewal as a therapeutic target in human colorectal cancer. Nat Med. 2014;20:29–36.PubMedCrossRef
80.
Zurück zum Zitat Srinivasan M, Bharali DJ, Sudha T, Khedr M, Guest I, Sell S, et al. Downregulation of Bmi1 in breast cancer stem cells suppresses tumor growth and proliferation. Oncotarget. 2017;8:38731–42.PubMedPubMedCentralCrossRef Srinivasan M, Bharali DJ, Sudha T, Khedr M, Guest I, Sell S, et al. Downregulation of Bmi1 in breast cancer stem cells suppresses tumor growth and proliferation. Oncotarget. 2017;8:38731–42.PubMedPubMedCentralCrossRef
82.
Zurück zum Zitat •• Chin YT, Wei PL, Ho Y, Nana AW, Changou CA, Chen YR, et al. Thyroxine inhibits resveratrol-caused apoptosis by PD-L1 in ovarian cancer cells. Endocr Relat Cancer. 2018;25:533–45 Authors demonstrated the potential impact of thyroid hormones on cancer apoptosis. T4 inhibited COX-2-dependent apoptosis in ovarian cancer cells by retaining inducible COX-2 with PD-L1 in the cytoplasm. These findings provide new insights into the effect of T4 antagonizing factors on cancer properties.PubMedCrossRef •• Chin YT, Wei PL, Ho Y, Nana AW, Changou CA, Chen YR, et al. Thyroxine inhibits resveratrol-caused apoptosis by PD-L1 in ovarian cancer cells. Endocr Relat Cancer. 2018;25:533–45 Authors demonstrated the potential impact of thyroid hormones on cancer apoptosis. T4 inhibited COX-2-dependent apoptosis in ovarian cancer cells by retaining inducible COX-2 with PD-L1 in the cytoplasm. These findings provide new insights into the effect of T4 antagonizing factors on cancer properties.PubMedCrossRef
83.
Zurück zum Zitat Cremaschi GA, Cayrol F, Sterle HA, Diaz Flaque MC, Barreiro Arcos ML. Thyroid hormones and their membrane receptors as therapeutic targets for T cell lymphomas. Pharmacol Res. 2016;109:55–63.PubMedCrossRef Cremaschi GA, Cayrol F, Sterle HA, Diaz Flaque MC, Barreiro Arcos ML. Thyroid hormones and their membrane receptors as therapeutic targets for T cell lymphomas. Pharmacol Res. 2016;109:55–63.PubMedCrossRef
84.
Zurück zum Zitat Davis PJ, Sudha T, Lin HY, Mousa SA. Thyroid hormone, hormone analogs, and angiogenesis. Compr Physiol. 2015;6:353–62.PubMedCrossRef Davis PJ, Sudha T, Lin HY, Mousa SA. Thyroid hormone, hormone analogs, and angiogenesis. Compr Physiol. 2015;6:353–62.PubMedCrossRef
85.
Zurück zum Zitat Lin HY, Chin YT, Yang YC, Lai HY, Wang-Peng J, Liu LF, et al. Thyroid hormone, cancer, and apoptosis. Compr Physiol. 2016;6:1221–37.PubMedCrossRef Lin HY, Chin YT, Yang YC, Lai HY, Wang-Peng J, Liu LF, et al. Thyroid hormone, cancer, and apoptosis. Compr Physiol. 2016;6:1221–37.PubMedCrossRef
86.
Zurück zum Zitat Pinto M, Soares P, Ribatti D. Thyroid hormone as a regulator of tumor induced angiogenesis. Cancer Lett. 2011;301:119–26.PubMedCrossRef Pinto M, Soares P, Ribatti D. Thyroid hormone as a regulator of tumor induced angiogenesis. Cancer Lett. 2011;301:119–26.PubMedCrossRef
87.
Zurück zum Zitat Shinderman-Maman E, Cohen K, Weingarten C, Nabriski D, Twito O, Baraf L, et al. The thyroid hormone-αvβ3 integrin axis in ovarian cancer: regulation of gene transcription and MAPK-dependent proliferation. Oncogene. 2016;35:1977–87.PubMedCrossRef Shinderman-Maman E, Cohen K, Weingarten C, Nabriski D, Twito O, Baraf L, et al. The thyroid hormone-αvβ3 integrin axis in ovarian cancer: regulation of gene transcription and MAPK-dependent proliferation. Oncogene. 2016;35:1977–87.PubMedCrossRef
88.
Zurück zum Zitat Bailey EB, Tantravahi SK, Poole A, Agarwal AM, Straubhar AM, Batten JA, et al. Correlation of degree of hypothyroidism with survival outcomes in patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors. Clin Genitourin Cancer. 2014;ed2015:e131–7. Bailey EB, Tantravahi SK, Poole A, Agarwal AM, Straubhar AM, Batten JA, et al. Correlation of degree of hypothyroidism with survival outcomes in patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors. Clin Genitourin Cancer. 2014;ed2015:e131–7.
89.
Zurück zum Zitat Cristofanilli M, Yamamura Y, Kau SW, Bevers T, Strom S, Patangan M, et al. Thyroid hormone and breast carcinoma. Primary hypothyroidism is associated with a reduced incidence of primary breast carcinoma. Cancer. 2005;103:1122–8.PubMedCrossRef Cristofanilli M, Yamamura Y, Kau SW, Bevers T, Strom S, Patangan M, et al. Thyroid hormone and breast carcinoma. Primary hypothyroidism is associated with a reduced incidence of primary breast carcinoma. Cancer. 2005;103:1122–8.PubMedCrossRef
90.
Zurück zum Zitat Nelson M, Hercbergs A, Rybicki L, Strome M. Association between development of hypothyroidism and improved survival in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 2006;132:1041–6.PubMedCrossRef Nelson M, Hercbergs A, Rybicki L, Strome M. Association between development of hypothyroidism and improved survival in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 2006;132:1041–6.PubMedCrossRef
91.
Zurück zum Zitat Schmidinger M, Vogl UM, Bojic M, Lamm W, Heinzl H, Haitel A, et al. Hypothyroidism in patients with renal cell carcinoma: blessing or curse? Cancer. 2011;117:534–44.PubMedCrossRef Schmidinger M, Vogl UM, Bojic M, Lamm W, Heinzl H, Haitel A, et al. Hypothyroidism in patients with renal cell carcinoma: blessing or curse? Cancer. 2011;117:534–44.PubMedCrossRef
92.
Zurück zum Zitat Davis PJ, Goglia F, Leonard JL. Nongenomic actions of thyroid hormone. Nat Rev Endocrinol. 2016;12:111–21.PubMedCrossRef Davis PJ, Goglia F, Leonard JL. Nongenomic actions of thyroid hormone. Nat Rev Endocrinol. 2016;12:111–21.PubMedCrossRef
94.
Zurück zum Zitat Davis PJ, Glinsky GV, Lin H-Y, Leith JT, Hercbergs A, Tang H-Y, et al. Cancer cell gene expression modulated from plasma membrane integrin αvβ3 by thyroid hormone and nanoparticulate tetrac. Front Endocrinol (Lausanne). 2015;5:240.CrossRef Davis PJ, Glinsky GV, Lin H-Y, Leith JT, Hercbergs A, Tang H-Y, et al. Cancer cell gene expression modulated from plasma membrane integrin αvβ3 by thyroid hormone and nanoparticulate tetrac. Front Endocrinol (Lausanne). 2015;5:240.CrossRef
95.
Zurück zum Zitat Yi H, Zeng D, Shen Z, Liao J, Wang X, Liu Y, et al. Integrin alphavbeta3 enhances β-catenin signaling in acute myeloid leukemia harboring Fms-like tyrosine kinase-3 internal tandem duplication mutations: implications for microenvironment influence on sorafenib sensitivity. Oncotarget. 2016;7:40387–97.PubMedPubMedCentralCrossRef Yi H, Zeng D, Shen Z, Liao J, Wang X, Liu Y, et al. Integrin alphavbeta3 enhances β-catenin signaling in acute myeloid leukemia harboring Fms-like tyrosine kinase-3 internal tandem duplication mutations: implications for microenvironment influence on sorafenib sensitivity. Oncotarget. 2016;7:40387–97.PubMedPubMedCentralCrossRef
96.
97.
Zurück zum Zitat Shi S, Zhou M, Li X, Hu M, Li C, Li M, et al. Synergistic active targeting of dually integrin alphavbeta3/CD44-targeted nanoparticles to B16F10 tumors located at different sites of mouse bodies. J Control Release. 2016;235:1–13.PubMedCrossRef Shi S, Zhou M, Li X, Hu M, Li C, Li M, et al. Synergistic active targeting of dually integrin alphavbeta3/CD44-targeted nanoparticles to B16F10 tumors located at different sites of mouse bodies. J Control Release. 2016;235:1–13.PubMedCrossRef
98.
Zurück zum Zitat Weingarten C, Jenudi Y, Tshuva RY, Moskovich D, Alfandari A, Hercbergs A, et al. The interplay between epithelial–mesenchymal transition (EMT) and the thyroid hormones–αvβ3 axis in ovarian cancer. Horm Cancer. 2018;9:22–32.PubMedCrossRef Weingarten C, Jenudi Y, Tshuva RY, Moskovich D, Alfandari A, Hercbergs A, et al. The interplay between epithelial–mesenchymal transition (EMT) and the thyroid hormones–αvβ3 axis in ovarian cancer. Horm Cancer. 2018;9:22–32.PubMedCrossRef
99.
Zurück zum Zitat Zhang P, Chen L, Song Y, Li X, Sun Y, Xiao Y, et al. Tetraiodothyroacetic acid and transthyretin silencing inhibit pro-metastatic effect of L-thyroxin in anoikis-resistant prostate cancer cells through regulation of MAPK/ERK pathway. Exp Cell Res. 2016;347:350–9.PubMedCrossRef Zhang P, Chen L, Song Y, Li X, Sun Y, Xiao Y, et al. Tetraiodothyroacetic acid and transthyretin silencing inhibit pro-metastatic effect of L-thyroxin in anoikis-resistant prostate cancer cells through regulation of MAPK/ERK pathway. Exp Cell Res. 2016;347:350–9.PubMedCrossRef
100.
Zurück zum Zitat Abou-El-Naga AM, Mutawa G, El-Sherbiny IM, Mousa SA. Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells. Int J Nanomedicine. 2018;13:8153–64.CrossRef Abou-El-Naga AM, Mutawa G, El-Sherbiny IM, Mousa SA. Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells. Int J Nanomedicine. 2018;13:8153–64.CrossRef
101.
Zurück zum Zitat •• Sudha T, Bharali DJ, Yalcin M, Darwish NH, Debreli Coskun M, Keating KA, et al. Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac. Int J Nanomedicine. 2017;12:1305–15 Authors discuss the potential impact of therapies that target integrin αvβ3. They demonstrated the feasibility of chemotherapy delivery using a nanoparticle system that achieved higher intratumoral concentrations and improved antitumor efficacy of chemotherapies than via the conventional administration route of these agents.PubMedCrossRef •• Sudha T, Bharali DJ, Yalcin M, Darwish NH, Debreli Coskun M, Keating KA, et al. Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac. Int J Nanomedicine. 2017;12:1305–15 Authors discuss the potential impact of therapies that target integrin αvβ3. They demonstrated the feasibility of chemotherapy delivery using a nanoparticle system that achieved higher intratumoral concentrations and improved antitumor efficacy of chemotherapies than via the conventional administration route of these agents.PubMedCrossRef
102.
Zurück zum Zitat Mousa SA, Glinsky GV, Lin HY, Ashur-Fabian O, Hercbergs A, Keating KA, et al. Contributions of thyroid hormone to cancer metastasis. Biomedicines. 2018;6:89.PubMedCentralCrossRef Mousa SA, Glinsky GV, Lin HY, Ashur-Fabian O, Hercbergs A, Keating KA, et al. Contributions of thyroid hormone to cancer metastasis. Biomedicines. 2018;6:89.PubMedCentralCrossRef
103.
Zurück zum Zitat Cai X, Zhu H, Li Y. Pkczeta, MMP2 and MMP9 expression in lung adenocarcinoma and association with a metastatic phenotype. Mol Med Rep. 2017;16:8301–6.PubMedCrossRef Cai X, Zhu H, Li Y. Pkczeta, MMP2 and MMP9 expression in lung adenocarcinoma and association with a metastatic phenotype. Mol Med Rep. 2017;16:8301–6.PubMedCrossRef
104.
Zurück zum Zitat Hong M, Cheng H, Song L, Wang W, Wang Q, Xu D, et al. Wogonin suppresses the activity of matrix metalloproteinase-9 and inhibits migration and invasion in human hepatocellular carcinoma. Molecules. 2018;23:384.PubMedCentralCrossRef Hong M, Cheng H, Song L, Wang W, Wang Q, Xu D, et al. Wogonin suppresses the activity of matrix metalloproteinase-9 and inhibits migration and invasion in human hepatocellular carcinoma. Molecules. 2018;23:384.PubMedCentralCrossRef
105.
Zurück zum Zitat Tauro M, Lynch CC. Cutting to the chase: how matrix metalloproteinase-2 activity controls breast-cancer-to-bone metastasis. Cancers (Basel). 2018;10:185.CrossRef Tauro M, Lynch CC. Cutting to the chase: how matrix metalloproteinase-2 activity controls breast-cancer-to-bone metastasis. Cancers (Basel). 2018;10:185.CrossRef
106.
Zurück zum Zitat Cohen K, Flint N, Shalev S, Erez D, Baharal T, Davis PJ, et al. Thyroid hormone regulates adhesion, migration and matrix metalloproteinase 9 activity via αvβ3 integrin in myeloma cells. Oncotarget. 2014;5:6312–22.PubMedPubMedCentralCrossRef Cohen K, Flint N, Shalev S, Erez D, Baharal T, Davis PJ, et al. Thyroid hormone regulates adhesion, migration and matrix metalloproteinase 9 activity via αvβ3 integrin in myeloma cells. Oncotarget. 2014;5:6312–22.PubMedPubMedCentralCrossRef
107.
Zurück zum Zitat Bridoux A, Khan RA, Chen C, Cheve G, Cui H, Dyskin E, et al. Design, synthesis, and biological evaluation of bifunctional thyrointegrin inhibitors: new anti-angiogenesis analogs. J Enzyme Inhib Med Chem. 2011;26:871–82.PubMedCrossRef Bridoux A, Khan RA, Chen C, Cheve G, Cui H, Dyskin E, et al. Design, synthesis, and biological evaluation of bifunctional thyrointegrin inhibitors: new anti-angiogenesis analogs. J Enzyme Inhib Med Chem. 2011;26:871–82.PubMedCrossRef
108.
Zurück zum Zitat Mousa SA, Mousa AS. Angiogenesis inhibitors: current & future directions. Curr Pharm Des. 2004;10:1–9.PubMedCrossRef Mousa SA, Mousa AS. Angiogenesis inhibitors: current & future directions. Curr Pharm Des. 2004;10:1–9.PubMedCrossRef
109.
Zurück zum Zitat Davis PJ, Mousa SA, Lin HY. Tetraiodothyroacetic acid (tetrac), integrin αvβ3 and disabling of immune checkpoint defense. Future Med Chem. 2018;10:1637–9.PubMedCrossRef Davis PJ, Mousa SA, Lin HY. Tetraiodothyroacetic acid (tetrac), integrin αvβ3 and disabling of immune checkpoint defense. Future Med Chem. 2018;10:1637–9.PubMedCrossRef
110.
Zurück zum Zitat Mousa SA, Rajabi M, inventors. Non-cleaveable polymer conjugated with αvβ3 integrin thyroid antagonists. USA patent 10, 201,616. 2019. Mousa SA, Rajabi M, inventors. Non-cleaveable polymer conjugated with αvβ3 integrin thyroid antagonists. USA patent 10, 201,616. 2019.
111.
Zurück zum Zitat Rajabi M, Godugu K, Sudha T, Bharali DJ, Mousa SA. Triazole modified tetraiodothyroacetic acid conjugated to polyethylene glycol: High affinity thyrointegrin αvβ3 antagonist with potent anticancer activities in glioblastoma multiforme. Bioconj Chem. 2019;30:3087-97. Rajabi M, Godugu K, Sudha T, Bharali DJ, Mousa SA. Triazole modified tetraiodothyroacetic acid conjugated to polyethylene glycol: High affinity thyrointegrin αvβ3 antagonist with potent anticancer activities in glioblastoma multiforme. Bioconj Chem. 2019;30:3087-97.
Metadaten
Titel
Current and Future Molecular Targets for Acute Myeloid Leukemia Therapy
verfasst von
Shaheedul A. Sami, PharmD
Noureldien H. E. Darwish, MD PhD
Amanda N. M. Barile, PharmD
Shaker A. Mousa, PhD
Publikationsdatum
01.01.2020
Verlag
Springer US
Erschienen in
Current Treatment Options in Oncology / Ausgabe 1/2020
Print ISSN: 1527-2729
Elektronische ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-019-0694-6

Weitere Artikel der Ausgabe 1/2020

Current Treatment Options in Oncology 1/2020 Zur Ausgabe

Leukemia (PH Wiernik, Section Editor)

The Microbiota in Hematologic Malignancies

Lower Gastrointestinal Cancers (AB Benson, Section Editor)

Locally Advanced Rectal Cancer: Treatment Approach in Elderly Patients

Palliative and Supportive Care (MP Davis, Section Editor)

Chemotherapy-Induced Sarcopenia

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.