Priming tumor blood vessels and the microenvironment
short project description
The vasculature and stroma in tumors and metastases are highly heterogeneous, compromising efficient drug delivery. Priming tumor blood vessels and the microenvironment in tumors and metastases may help to improve drug delivery and therapeutic efficacy (1). We recently showed that treatment with the anti-anemia drug erythropoietin (EPO) induces vascular remodelling, enhances tumor perfusion, and improves the delivery and efficacy of carboplatin (2). In this context, we employed multiparametric imaging techniques to characterize the microenvironment in tumors and metastasis during drug treatment (3-5).
We hypothesize that vascular and microenvironmental priming increases DDS accumulation and efficacy. Specific aims are:
- to study how EPO and other clinically relevant vascular and stromal priming agents influence the tumor microenvironment and tumor heterogeneity in orthotopic metastasizing colon cancer models; and
- to investigate the effects of the priming agents on the accumulation and penetration of DDS in primary tumors and metastases, as well as on their therapeutic efficacy.
Ojha T, Pathaka V, Shi Y, Moonen C, Hennink W, Storm G, Kiessling F, Lammers T. Pharmacological and Physical Vessel Modulation Strategies to Improve EPR-mediated Drug Targeting to Tumors. Adv Drug Del Rev 2017, DOI: 10.1016/j.addr.2017.07.007
Doleschel D, Rix A, Arns S, Palmowski K, Gremse F, Merkle R, Salopiata F, Klingmuller U, Jarsch M, Kiessling F, Lederle W: Erythropoietin improves the accumulation and therapeutic effects of carboplatin by enhancing tumor vascularization and perfusion. Theranostics 2015, 5(8):905-918.
Al Rawashdeh W, Arns S, Gremse F, Ehling J, Knuchel-Clarke R, Kray S, Spoler F, Kiessling F, Lederle W: Optical tomography of MMP activity allows a sensitive noninvasive characterization of the invasiveness and angiogenesis of SCC xenografts. Neoplasia 2014, 16(3):235-246.
Baetke SC, Rix A, Tranquart F, Schneider R, Lammers T, Kiessling F, Lederle W: Squamous Cell Carcinoma Xenografts: Use of VEGFR2-targeted Microbubbles for Combined Functional and Molecular US to Monitor Antiangiogenic Therapy Effects. Radiology 2016, 278(2):430-440.
Abou-Elkacem L, Arns S, Brix G, Gremse F, Zopf D, Kiessling F, Lederle W: Regorafenib inhibits growth, angiogenesis and metastasis in a highly aggressive orthotopic colon cancer model. Mol Cancer Ther 2013, 12(7):1322-1331.