Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Die Highlights vom Kongress des American College of Cardiology 2024

Im April diskutierten die Herz-Kreislauf-Spezialisten aus der ganzen Welt auf dem  Kongress des American College of Cardiology (ACC) u.a. neue Therapieansätze bei akutem Myokardinfarkt, koronarer Herzerkrankung, kardiogenem Schock oder Aortenklappenstenose. In unserem Kongress-Dossier haben wir für Sie Berichte über die „Late-Breaking Trials“ und andere wichtige Studien zusammengestellt. 
Erweiterte Suche
Anmelden
nach oben
Current Breast Cancer Reports
Erschienen in: Current Breast Cancer Reports 1/2011

01.03.2011

Insulin-Like Growth Factor Pathway–Targeted Therapy in Breast Cancer

verfasst von: Saad J. Sirop, Paul Haluska

Erschienen in: Current Breast Cancer Reports | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

The insulin-like growth factor (IGF) pathway plays an important role in cancer development, survival, metastasis, and resistance to antineoplastic therapies in various malignancies. Components of the IGF pathway are potential targets for novel anticancer therapy. In breast cancer, preclinical and clinical data suggest that IGF signaling is critical for tumor growth and resistance to therapy, leading to poor prognosis. There is also evidence of cross-talk between IGF, estrogen, erbB, and mTOR pathways; a potential mechanism of cancer resistance to hormonal or HER2-targeted therapy. This review discusses the rationale and strategies being evaluated in the clinical development of targeting the IGF pathway. It highlights the potential interactions between the IGF pathway and other therapies in breast cancer, and also focuses on the completed and ongoing clinical trials of different IGF pathway–targeted therapies in breast cancer.
Literatur
1.
Carboni JM, Lee AV, Hadsell DL, et al. Tumor development by transgenic expression of a constitutively active insulin-like growth factor I receptor. Cancer Res. 2005;65(9):3781–7.CrossRefPubMed
2.
Lopez T, Hanahan D. Elevated levels of IGF-1 receptor convey invasive and metastatic capability in a mouse model of pancreatic islet tumorigenesis. Cancer Cell. 2002;1(4):339–53.CrossRefPubMed
3.
Yuen JS, Macaulay VM. Targeting the type 1 insulin-like growth factor receptor as a treatment for cancer. Expert Opin Ther Targets. 2008 May;12(5):589–603.CrossRefPubMed
4.
Ryan PD, Goss PE. The emerging role of the insulin-like growth factor pathway as a therapeutic target in cancer. Oncologist 2008 Jan;13(1):16–24.CrossRefPubMed
5.
• Belfiore A, Frasca F, Pandini G, et al. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr Rev. 2009 Oct;30(6):586–623. This work describes the role of the insulin receptor in IGF signaling. It is an outstanding review that highlights the importance of IGF-1R/InsR hybrids and InsR isoforms, which has implications for targeting strategies.CrossRefPubMed
6.
Frasca F, Pandini G, Scalia P, et al. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells.. Mol Cell Biol 1999 May;19(5):3278–88.PubMed
7.
Pandini G, Frasca F, Mineo R, et al. Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem 2002 Oct 18;277(42):39684–95.CrossRefPubMed
8.
Renehan AG, Zwahlen M, Minder C, et al. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 2004 Apr 24;363(9418):1346–53CrossRefPubMed
9.
Chan JM, Stampfer MJ, Giovannucci E, et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 1998 Jan 23;279(5350):563–6.CrossRefPubMed
10.
Hankinson SE, Willett WC, Colditz GA, et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 1998 May 9;351(9113):1393–6.CrossRefPubMed
11.
Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010 Sep–Oct;60(5):277–300.CrossRefPubMed
12.
Hartog H, Wesseling J, Boezen HM, et al. The insulin-like growth factor 1 receptor in cancer: old focus, new future. Eur J Cancer. 2007 Sep;43(13):1895–904.CrossRefPubMed
13.
Sciacca L, Costantino A, Pandini G, et al. Insulin receptor activation by IGF-II in breast cancers: evidence for a new autocrine/paracrine mechanism. Oncogene 1999 Apr 15;18(15):2471–9.CrossRefPubMed
14.
Rinaldi S, Peeters PH, Berrino F, et al. IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer. 2006 Jun;13(2):593–605.CrossRefPubMed
15.
• Creighton CJ, Casa A, Lazard Z, et al. Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis. J Clin Oncol. 2008 Sep 1;26(25):4078–85. This work identified a DNA microarray signature that indicated active IGF signaling. The presence of the signature correlates with poor breast cancer outcomes, suggesting benefit from targeting IGF signaling.CrossRefPubMed
16.
Mathieu MC, Clark GM, Allred DC, et al. Insulin receptor expression and clinical outcome in node-negative breast cancer. Proc Assoc Am Physicians. 1997 Nov;109(6):565–71.PubMed
17.
Tan QW, Brito C, De León M, et al. Insulin-like growth factors I and II receptors in the breast cancer survival disparity among African-American women. Growth Horm IGF Res. 2010 Jun;20(3):245–54.CrossRefPubMed
18.
Litzenburger BC, Tsimelzon A, Hilsenbeck SG, et al. High IGF-IR Activity in Triple-Negative Breast Cancer Cell Lines Correlates with Sensitivity to IGF-IR Inhibitor BMS-754807 in This Subtype of Human Breast Cancer. San Antonio Breast Cancer Symposium Dec 9–13, 2009, San Antonio, Texas, abstract 1132.
19.
Chu KC, Anderson WF, Fritz A, et al. Frequency distributions of breast cancer characteristics classified by estrogen receptor and progesterone receptor status for eight racial/ethnic groups. Cancer. 2001;92(1):37–45.CrossRefPubMed
20.
Baum M, Budzar AU, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial. Lancet. 2002 Jun 22;359(9324):2131–9CrossRefPubMed
21.
MacGregor JI, Jordan VC. Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev. 1998;50(2):151–96.PubMed
22.
Clarke RB, Howell A, Anderson E. Type I insulin-like growth factor receptor gene expression in normal human breast tissue treated with oestrogen and progesterone. Br J Cancer. 1997;75(2):251–7.CrossRefPubMed
23.
Hamelers IH, van Schaik RF, van Teeffelen HA, et al. Synergistic proliferative action of insulin-like growth factor I and 17 beta-estradiol in MCF-7S breast tumor cells. Exp Cell Res. 2002 Feb 1;273(1):107–17.CrossRefPubMed
24.
Wiseman LR, Johnson MD, Wakeling AE, et al. Type I IGF receptor and acquired tamoxifen resistance in oestrogen-responsive human breast cancer cells. Eur J Cancer. 1993;29A(16):2256–64.CrossRefPubMed
25.
Parisot JP, Hu XF, DeLuise M, et al. Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line. Br J Cancer. 1999 Feb;79(5–6):693–700.CrossRefPubMed
26.
Cohen BD, Baker DA, Soderstrom C, et al. Combination therapy enhances the inhibition of tumor growth with the fully human anti-type 1 insulin-like growth factor receptor monoclonal antibody CP-751,871. Clin Cancer Res. 2005 Mar 1;11(5):2063–73.CrossRefPubMed
27.
Weroha SJ, Haluska P. IGF-1 receptor inhibitors in clinical trials—early lessons. J Mammary Gland Biol Neoplasia. 2008 Dec;13(4):471–83.CrossRefPubMed
28.
Haluska P, Hou X, Huang F, et al. Complete IGF Signaling Blockade by the Dual-Kinase Inhibitor, BMS-754807, Is Sufficient To Overcome Tamoxifen and Letrozole Resistance In Vitro and In Vivo. San Antonio Breast Cancer Symposium Dec 9–13, 2009, San Antonio, Texas, abstract 402.
29.
Massarweh S, Osborne CK, Creighton CJ, et al. Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function. Cancer Res. 2008 Feb 1;68(3):826–33.CrossRefPubMed
30.
Morgillo F, Kim WY, Kim ES, et al. Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib. Clin Cancer Res. 2007;13:2795–803.CrossRefPubMed
31.
Jones HE, Goddard L, Gee JM, et al. Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells. Endocr Relat Cancer 2004 Dec;11(4):793–814.CrossRefPubMed
32.
Haluska P, Carboni JM, TenEyck C, et al. HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924. Mol Cancer Ther. 2008;7(9):2589–98.CrossRefPubMed
33.
Huang X, Gao L, Wang S, et al. Heterotrimerization of the growth factor receptors erbB2, erbB3, and insulin-like growth factor-i receptor in breast cancer cells resistant to herceptin. Cancer Res. 2010 Feb 1;70(3):1204–14CrossRefPubMed
34.
Garcia JM, Silva J, Pena C et al. Promoter methylation of the PTEN gene is a common molecular change in breast cancer. Genes Chromosomes Cancer 2004; 41: 117–124.CrossRefPubMed
35.
Tsutsui S, Inoue H, Yasuda K et al. Reduced expression of PTEN protein and its prognostic implications in invasive ductal carcinoma of the breast. Oncology 2005; 68:398–404.CrossRefPubMed
36.
Chan S, Scheulen ME, Johnston S et al. Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol 2005; 23: 5314–5322.CrossRefPubMed
37.
O’Reilly KE, Rojo F, She Q-B et al. mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt. Cancer Res 2006; 66: 1500–1508.CrossRefPubMed
38.
Wan X, Harkavy B, Shen N et al. Rapamycin induces feedback activation of Akt signaling through an IGF-IR-dependent mechanism. Oncogene 2007; 26: 1932–1940.CrossRefPubMed
39.
• Haluska P, Shaw HM, Batzel GN, et al. Phase I dose escalation study of the anti insulin-like growth factor-I receptor monoclonal antibody CP-751,871 in patients with refractory solid tumors. Clin Cancer Res. 2007 Oct 1;13(19):5834–40. This is the first report of an IGF-1R–targeting agent in patients with cancer. It demonstrated the feasibility of administering an IGF-1R monoclonal antibody and the metabolic consequences.CrossRefPubMed
40.
Lacy MQ, Alsina M, Fonseca R, et al. Phase I, pharmacokinetic and pharmacodynamic study of the anti-insulinlike growth factor type 1 Receptor monoclonal antibody CP-751,871 in patients with multiple myeloma. J Clin Oncol. 2008 Jul 1;26(19):3196–203.CrossRefPubMed
41.
Karp DD, Paz-Ares LG, Novello S, et al. Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP-751,871 in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non-small-cell lung cancer. J Clin Oncol. 2009 May 20;27(15):2516–22.CrossRefPubMed
42.
Olmos D, Postel-Vinay S, Molife LR, et al. Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody Figitumumab (CP-751,871) in patients with sarcoma and Ewing’s sarcoma: a phase 1 expansion cohort study. Lancet Oncol. 2010 Feb; 11(2):129–35.CrossRefPubMed
43.
Molife LR, Fong PC, Paccagnella L, et al. The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study. Br J Cancer. 2010 Jul 27;103(3):332–9.CrossRefPubMed
44.
Quek RH., Morgan JA, Shapiro G, et al. Combination mTOR+IGF-IR inhibition: Phase I trial of everolimus and CP-751871 in patients (pts) with advanced sarcomas and other solid tumors. J Clin Oncol 28:15s, 2010 (suppl; abstr 10002).
45.
Ryan PD, Neven P, Dirix LY, et al. Safety of the anti-IGF-1R antibody CP-751,871 in combination with exemestane in patients with advanced breast cancer. San Antonio Breast Cancer Symposium, Dec 10–14, 2008, San Antonio, Texas, abstract 2136.
46.
Dallas NA, Xia L, Fan F, et al. Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res. 2009 Mar 1; 69(5):1951–7.CrossRefPubMed
47.
Zhang H, Sachdev D, Wang C, et al. Detection and downregulation of type I IGF receptor expression by antibody-conjugated quantum dots in breast cancer cells. Breast Cancer Res Treat. 2009 Mar; 114(2):277–85.CrossRefPubMed
48.
Kurzrock R, Patnaik A, Aisner J, et al. A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors. Clin Cancer Res. 2010 Apr 15;16(8):2458–65.CrossRefPubMed
49.
Higano CS, Yu EY, Whiting SH, et al. A phase I, first in man study of weekly IMC-A12, a fully human insulin like growth factor-I receptor IgG1 monoclonal antibody, in patients with advanced solid tumors. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 3505.
50.
Reidy DL, Vakiani E, Fakih MG, et al. Randomized, phase II study of the insulin-like growth factor-1 receptor inhibitor IMC-A12, with or without cetuximab, in patients with cetuximab- or panitumumab-refractory metastatic colorectal cancer. J Clin Oncol. 2010 Sep 20;28(27):4240–6.CrossRefPubMed
51.
Rajan A, Berman AW, Kelly RJ, et al. Phase II study of the insulin-like growth factor-1 receptor (IGF-1R) antibody cixutumumab (C) in patients (pts) with thymoma (T) and thymic carcinoma (TC). J Clin Oncol 28, 2010 (suppl; abstr e17525).
52.
Tolcher AW, Sarantopoulos J, Patnaik A, et al. Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1. J Clin Oncol. 2009 Dec 1;27(34):5800–7.CrossRefPubMed
53.
Sarantopoulos J, Mita AC, Mulay M, et al. A phase IB study of AMG 479, a type 1 insulin-like growth factor receptor (IGF1R) antibody, in combination with panitumumab (P) or gemcitabine (G). J Clin Oncol 26: 2008 (May 20 suppl; abstr 3583).
54.
Atzori F, Tabernero J, Cervantes A, et al. A phase I, pharmacokinetic (PK) and pharmacodynamic (PD) study of weekly (qW) MK-0646, an insulin-like growth factor-1 receptor (IGF1R) monoclonal antibody (MAb) in patients (pts) with advanced solid tumors. J Clin Oncol 26: 2008 (May 20 suppl; abstr 3519).
55.
Hidalgo M, Tirado Gomez M, Lewis N, et al. A phase I study of MK-0646, a humanized monoclonal antibody against the insulin-like growth factor receptor type 1 (IGF1R) in advanced solid tumor patients in a q2 wk schedule. J Clin Oncol 26: 2008 (May 20 suppl; abstr 3520).
56.
Javle MM, Varadhachary GR, Shroff RT, et al. Phase I/II study of MK-0646, the humanized monoclonal IGF-1R antibody in combination with gemcitabine or gemcitabine plus erlotinib (E) for advanced pancreatic cancer. J Clin Oncol 28:15s, 2010 (suppl; abstr 4039).
57.
Reidy L, Hollywood E, Segal M, et al. A phase II clinical trial of MK-0646, an insulin-like growth factor-1 receptor inhibitor (IGF-1R), in patients with metastatic well-differentiated neuroendocrine tumors (NETs). J Clin Oncol 28:15s, 2010 (suppl; abstr 4163).CrossRef
58.
Di Cosimo S, Bendell JC, Cervantes-Ruiperez A, et al. A phase I study of the oral mTOR inhibitor ridaforolimus (RIDA) in combination with the IGF-1R antibody dalotozumab (DALO) in patients (pts) with advanced solid tumors. J Clin Oncol 28:15s, 2010 (suppl; abstr 3008).
59.
Desai J, Solomon BJ, Davis ID, et al. Phase I dose-escalation study of daily BMS-754807, an oral, dual IGF-1R/insulin receptor (IR) inhibitor in subjects with solid tumors. J Clin Oncol 28:15s, 2010 (suppl; abstr 3104).
60.
Macaulay VM, Middleton MR, Eckhardt SG, et al. Phase I study of OSI-906, dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR) in combination with erlotinib (E) in patients with advanced solid tumors. J Clin Oncol 28:15s, 2010 (suppl; abstr 3016).
61.
Evans T, Lindsay CR, Chan E, et al. Phase I dose-escalation study of continuous oral dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR), in patients with advanced solid tumors. J Clin Oncol 28:15s, 2010 (suppl; abstr 2531).
62.
Von Mehren M, Britten C, Lear K, et al. Phase I, dose-escalation study of BIIB022 (anti-IGF-1R antibody) in advanced solid tumors. J Clin Oncol 28:15s, 2010 (suppl; abstr 2612).
63.
Carden CP, Kim ES, Jones RL, et al. Phase I study of intermittent dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR) in patients with advanced solid tumors. J Clin Oncol 28:15s, 2010 (suppl; abstr 2530).
64.
O’Donnell R, El-Khoueiry AB, Lenz H, et al. A phase I trial of escalating doses of the anti-IGF-1R monoclonal antibody (mAb) cixutumumab (IMC-A12) and sorafenib for treatment of advanced hepatocellular carcinoma (HCC). J Clin Oncol 28:15s, 2010 (suppl; abstr TPS212).
65.
Rathkopf DE, Danila DC, Chudow JJ, et al. Anti-insulin-like growth factor-1 receptor (IGF-IR) monoclonal antibody cixutumumab plus mammalian target of rapamycin (mTOR) inhibitor temsirolimus in metastatic castration-resistant prostate cancer (CRPC). J Clin Oncol 28:15s, 2010 (suppl; abstr TPS242).
66.
Busaidy N, Kurzrock R, LoRusso P, et al. Hyperglycemia, hypertriglyceridemia, and hypercholesterolemia in a phase I trial of the combination of an mTOR inhibitor and IGF-1 receptor inhibitor. J Clin Oncol 28:15s, 2010 (suppl; abstr 2597).
Metadaten
Titel
Insulin-Like Growth Factor Pathway–Targeted Therapy in Breast Cancer
verfasst von
Saad J. Sirop
Paul Haluska
Publikationsdatum
01.03.2011
Verlag
Current Science Inc.
Erschienen in
Current Breast Cancer Reports / Ausgabe 1/2011
Print ISSN: 1943-4588
Elektronische ISSN: 1943-4596
DOI
https://doi.org/10.1007/s12609-010-0030-4

Weitere Artikel der Ausgabe 1/2011

Current Breast Cancer Reports 1/2011 Zur Ausgabe

ReviewPaper

Epigenetic Therapy in Breast Cancer

ReviewPaper

Hedgehog Pathway Inhibitors: Potential Applications in Breast Cancer

ReviewPaper

Management of Aromatase Inhibitor-Resistant Disease with Estrogen, Selective Estrogen Receptor Down-Regulators, and Other Agents

ReviewPaper

PARP Inhibitors

ReviewPaper

Targeted Therapies for HER2 Breast Cancer: A View of the Landscape

Clinical Trial Report

Endocrine Therapy Plus Zoledronic Acid in Premenopausal Breast Cancer: Review of a Clinical Trial

Neu im Fachgebiet Onkologie

Mammakarzinom: Brustdichte beeinflusst rezidivfreies Überleben

26.05.2024 Mammakarzinom Nachrichten

Frauen, die zum Zeitpunkt der Brustkrebsdiagnose eine hohe mammografische Brustdichte aufweisen, haben ein erhöhtes Risiko für ein baldiges Rezidiv, legen neue Daten nahe.

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

Das sind die führenden Symptome junger Darmkrebspatienten

23.05.2024 Leitsymptome in der Hausarztpraxis Nachrichten

Darmkrebserkrankungen in jüngeren Jahren sind ein zunehmendes Problem, das häufig längere Zeit übersehen wird, gerade weil die Patienten noch nicht alt sind. Welche Anzeichen Ärzte stutzig machen sollten, hat eine Metaanalyse herausgearbeitet.

Update Onkologie

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

Newsletter bestellen
Bildnachweise