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
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
Erweiterte Suche
Anmelden
nach oben
Clinical and Translational Oncology
Erschienen in: Clinical and Translational Oncology 7/2016

11.12.2015 | Review Article

Targeting the microenvironment of pancreatic cancer: overcoming treatment barriers and improving local immune responses

verfasst von: J. Strauss, C. Alewine, W. D. Figg, A. Duffy

Erschienen in: Clinical and Translational Oncology | Ausgabe 7/2016

Einloggen, um Zugang zu erhalten

Abstract

Historically, patients diagnosed with metastatic pancreatic cancer have faced a grim prognosis. The survival benefit seen with systemic chemotherapies and even combinations thereof have been disappointing. However, growing data suggest that the microenvironment of pancreatic cancer may be contributing to this poor prognosis. This microenvironment has a dense fibrotic stroma, and is hypoxic and highly immunosuppressive, all of which pose barriers to treatment. Newer strategies looking to disrupt the fibrotic stroma, target hypoxic areas, and improve local immune responses in the tumor microenvironment are currently undergoing clinical evaluation and seem to offer great promise. In addition to these therapies, preclinical work evaluating novel cytotoxic agents including nanoparticles has also been encouraging. While much research still needs to be done, these strategies offer new hope for patients with pancreatic cancer.
Literatur
1.
2.
3.
Artinyan A, Soriano PA, Prendergast C, Low T, Ellenhorn JD, Jim J. The anatomic location of pancreatic cancer is a prognostic factor for survival. HPB (Oxford). 2008;10(5):371–6.CrossRefPubMedPubMedCentral
4.
Sinn M, Liersch T, Gellert K, Messmann H, Bechstein W, Walschmidt D, et al. CONKO-005: adjuvant therapy in R0 resected pancreatic cancer patients with gemcitabine plus Erlotinib vs. Gemcitabine for 24 weeks. ASCO 2015. J Clin Oncol 2015;33 (suppl; abstr 4007).
5.
Burris HA III, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.PubMed
6.
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(15):1960–6.
7.
8.
Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouran Y, et al. FOLFIRINOX vs. gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMed
9.
Von Hoff D, Ervin T, Arena F, Chiorean G, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.CrossRef
10.
Hagg J, Howells LM, Garcea G, Metcalfe MS, Steward WP, Dennison AR, et al. Pancreatic stellate cells and pancreas cancer: current perspectives and future strategies. Eur J Cancer. 2014;50(15):2570–82.
11.
Dangi-Garimella S, Krantz SB, Barron MR, Shields MA, Heiferman MJ, Grippo PJ, et al. Three-dimensional collagen I promotes gemcitabine resistance in pancreatic cancer through MT1-MMP-mediated expression of HMGA2. Cancer Res. 2011;71(3):1019–28.CrossRefPubMed
12.
Neesse A, Frese KK, Bapiro TE, Nakagawa T, Sternlicht M, Seeley T, et al. CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer. Proc Natl Acad Sci U S A. 2013;110:12325–30.CrossRefPubMedPubMedCentral
13.
Provenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD, Hingorani SR. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell. 2012;21:418–29.CrossRefPubMedPubMedCentral
14.
Hingorani SR, Harris WP, Hendifar AE, Bullock AJ, Wu XW, Huang Y, et al. High response rate and PFS with PEGPH20 added to nab-paclitaxel/gemcitabine in stage IV previously untreated pancreatic cancer patients with high-HA tumors: Interim results of a randomized phase II study. J Clin Oncol. 2015;33 (suppl; abstr 4006).
15.
Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). JCO. 2010;28(22):3617–22.CrossRef
16.
Van Cutsem E, Vervenne WL, Bennouna J, Humblet Y, Gill S, Van Laethem JL, et al. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. JCO. 2009;27(13):2231–7.CrossRef
17.
Borad M, Reddy SG, Bahary N, Uronis HE, Sigal D, Cohn AL, et al. Randomized Phase II trial of gemcitabine plus th-302 vs. gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2015;33(13):1475–81.
18.
Hiraoka N, Onozato K, Kosuge T, Hirohashi S. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res 2006;12(18):5423–34.
19.
Kurahara H, Shinchi H, Mataki Y, Maemura K, Noma H, Kubo F, et al. Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res. 2011;167(2):e211–9.
20.
Shibuya KC, Goel VK, Xiong W, Sham JG, Pollack SM, Leahy AM, et al. Pancreatic ductal adenocarcinoma contains an effector and regulatory immune cell infiltrate that is altered by multimodal neoadjuvant treatment. PLoS One 2014;9(5):e96565.
21.
Geng L, Huang D, Qian Y, Deng J, Li D, Zhang J, et al. B7-H1 up-regulated expression in human pancreatic carcinoma tissue associates with tumor progression. J Cancer Res Clin Oncol. 2008;134:1021–7.
22.
Truty MJ, Urrutia R. Basics of TGF-ß and Pancreatic Cancer. Pancreatology. 2007;7(5–6):423–35.
23.
Wrszesinski S, Wan YY, Flavell RA. Transforming growth factor-beta and the immune response: implications for anticancer therapy. Clin Cancer Res. 2007;13(18 Pt 1):5262–70.
24.
Oettle H, Seufferlein T, Luger T, Schmid RM, von Wichert G, Endlicher E, et al. Final results of a phase I/II study in patients with pancreatic cancer, malignant melanoma, and colorectal carcinoma with trabedersen. J Clin Oncol. 2012;30 (suppl; abstr 4034).
25.
Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011;331:1612–6.CrossRefPubMedPubMedCentral
26.
Brahmer JR, Scott TS, Chow LQM, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. NEJM. 2012;366(26):2455–65.CrossRefPubMedPubMedCentral
27.
Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, et al. Phase 2 trial of single agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010;33(8):828–33.CrossRefPubMed
28.
Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22.CrossRefPubMed
29.
Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, et al. OS analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28(7):1099–105.CrossRefPubMedPubMedCentral
30.
Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, et al. Ipilimumab vs. placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15(7):700–12.
31.
Hodi S, O’day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. NEJM. 2010;363(8):711–23.CrossRefPubMedPubMedCentral
32.
Rahma OE, Duffy A, Liewehr DJ, Steinberg SM, Greten TF. Second-line treatment in advanced pancreatic cancer: a comprehensive analysis of published clinical trials. Ann Oncol. 2013;24(8):1972–9.CrossRefPubMedPubMedCentral
33.
Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res. 2005;11:6713.CrossRefPubMed
34.
Le HK, Graham L, Cha E, Morales JK, Manjili MH, Bear HD. Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice. Int Immunopharmacol. 2009;9(7–8):900–9.CrossRefPubMed
35.
Garnett CT, Palena C, Chakraborty M, Tsang KY, Schlom J, Hodge JW. Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes. Cancer Res. 2004;64:7985–94.CrossRefPubMed
36.
Chakraborty M, Abrams SI, Coleman CN, Camphausen K, Schlom J, Hodge JW. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res. 2004;64:4328–37.CrossRefPubMed
37.
Chakraborty M, Abrams SI, Camphausen K, Liu K, Scott T, Coleman CN, et al. Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy. J Immunol. 2003;170:6338–47.CrossRefPubMed
38.
Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA. 2013;110:20212–7.CrossRefPubMedPubMedCentral
39.
40.
Lutz E, Yeo CJ, Lillemoe KD, Biedrzycki B, Kobrin B, Herman J, et al. A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma: a phase II trial of safety, efficacy, and immune activation. Ann Surg. 2011;253:328–35.CrossRefPubMedPubMedCentral
41.
Le DT, Brockstedt DG, Nir-Paz R, Hampl J, Mathur S, Nemunaitis J, et al. A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune induction. Clin Cancer Res. 2012;18:858–68.CrossRefPubMed
42.
Le D, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, et al. Safety and Survival With GVAX Pancreas Prime and Listeria Monocytogenes—expressing Mesothelin (CRS-207) Boost Vaccines for Metastatic Pancreatic Cancer. JCO 2015.
43.
Le D, Lutz E, Uram JN, Sugars EA, Onners B, Solt S, et al. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother. 2013;36:382–9.CrossRefPubMedPubMedCentral
44.
Kim SH, Castro F, Paterson Y, Gravekamp C. High efficacy of a Listeria-based vaccine against metastatic breast cancer reveals a dual mode of action. Cancer Res. 2009;69(14):5860–6.CrossRefPubMedPubMedCentral
45.
Quispe-Tintaya W, Chandra D, Jahangir A, Harris M, Casadevll A, Dadachoa E, et al. Nontoxic radioactive Listeria at is a highly effective therapy against metastatic pancreatic cancer. Proc Natl Acad Sci U S A. 2013;110 (21):8668–73
46.
47.
Cherukuri P, Curley SA. Use of nanoparticles for targeted, noninvasive thermal destruction of malignant cells. Methods Mol Biol. 2010;624:359–73.CrossRefPubMed
48.
Banobre-Lopez M, Teijeiro A, Rivas J. Magnetic nanoparticle-based hyperthermia for cancer treatment. Rep Pract Oncol Radiother. 2013;18(6):397–400.CrossRefPubMedPubMedCentral
49.
Basel MT, Balivada S, Wang H, Shrestha TB, Seo GM, Pyle M, et al. Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model. Int J Nanomedicine. 2012;7:297–306.CrossRefPubMedPubMedCentral
50.
Kossatz S, Ludwig R, Dahring H, Ettelt V, Rimkus G, Marciello M, et al. High therapeutic efficiency of magnetic hyperthermia in xenograft models achieved with moderate temperature dosages in the tumor area. Pharmaceutical Res. 2014;31(12):3274–88.CrossRef
51.
Wang L, Dong J, Ouyang W, Wang X, Tang J. Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles. Oncol Rep. 2012;27(3):719–26.PubMed
52.
Huang HS, Hainfeld JF. Intravenous magnetic nanoparticle cancer hyperthermia. Int J Nanomedicine. 2013;8:2521–32.PubMedPubMedCentral
Metadaten
Titel
Targeting the microenvironment of pancreatic cancer: overcoming treatment barriers and improving local immune responses
verfasst von
J. Strauss
C. Alewine
W. D. Figg
A. Duffy
Publikationsdatum
11.12.2015
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology / Ausgabe 7/2016
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-015-1459-8

Weitere Artikel der Ausgabe 7/2016

Clinical and Translational Oncology 7/2016 Zur Ausgabe

Research Article

Landscape of early clinical trials for childhood and adolescence cancer in Spain

Research Article

Clinical significance of ECT2 expression in tissue and serum of gastric cancer patients

Research Article

Can tumor regression grade influence survival outcome in ypT3 rectal cancer?

Research Article

Compliance to radiation therapy of head and neck cancer patients and impact on treatment outcome

Research Article

Clinical significance of TP53 (R72P) and MDM2 (T309G) polymorphisms in breast cancer patients

Research Article

Overexpression of Cathepsin L is associated with gefitinib resistance in non-small cell lung cancer

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 | NSCLC | Nachrichten

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

24.04.2024 | DGIM 2024 | Nachrichten

Bei Senioren mit Prostatakarzinom auf Anämie achten!

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

ICI-Therapie in der Schwangerschaft wird gut toleriert
weitere anzeigen

Update Onkologie

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

Newsletter bestellen