Influence of the vascular damaging agents DMXAA and ZD6126 on hypericin distribution and accumulation in RIF-1 tumors

Marysael, Thierry; Ni, Yicheng; Lerut, Evelyne; Witte, Peter de

doi:10.1007/s00432-011-1032-y

Cited by 13 publications

(11 citation statements)

References 27 publications

(34 reference statements)

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“…In support of our hypothesis, we observed increased drug delivery following pretreatment of tumors with VDA (2 hours prior to chemotherapy administration). In support of this approach, Marysael et al, have previously reported increased accumulation of the necrosis avid agent, Hypericin, when administered 24 hours after treatment with DMXAA (33). In our study, enhancement of therapeutic efficacy was dependent on the VDA dose employed.…”

Section: Discussionmentioning

confidence: 94%

Vascular priming enhances chemotherapeutic efficacy against head and neck cancer

et al. 2013

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Purpose The need to improve chemotherapeutic efficacy against head and neck squamous cell carcinomas (HNSCC) is well recognized. In this study, we investigated the potential of targeting the established tumor vasculature in combination with chemotherapy in head and neck cancer. Methods Experimental studies were carried out in multiple human HNSCC xenograft models to examine the activity of the vascular disrupting agent (VDA) 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in combination with chemotherapy. Multimodality imaging (magnetic resonance imaging, bioluminescence) in conjunction with drug delivery assessment (fluorescence microscopy), histopathology and microarray analysis was performed to characterize tumor response to therapy. Long-term treatment outcome was assessed using clinically-relevant end points of efficacy. Results Pretreatment of tumors with VDA prior to administration of chemotherapy increased intratumoral drug delivery and treatment efficacy. Enhancement of therapeutic efficacy was dependent on the dose and duration of VDA treatment but was independent of the chemotherapeutic agent evaluated. Combination treatment resulted in increased tumor cell kill and improvement in progression-free survival and overall survival in both ectopic and orthotopic HNSCC models. Conclusion Our results show that preconditioning of the tumor microenvironment with an antivascular agent primes the tumor vasculature and results in enhancement of chemotherapeutic delivery and efficacy in vivo. Further investigation into the activity of antivascular agents in combination with chemotherapy against HNSCC is warranted.

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Section: Discussionmentioning

confidence: 94%

Vascular priming enhances chemotherapeutic efficacy against head and neck cancer

et al. 2013

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“…However, preclinical studies suggest that following exposure to a VDA, only the center of the tumor becomes necrotic, with a viable rim remaining in the periphery. This rim of viable tumor cells is highly proliferative and has potential for tumor growth [20]. This phenomenon provides the rationale for developing combination therapy with VDAs and anti-angiogenesis or conventional cytotoxic drugs [21].…”

Section: Vascular Disrupting Agents (Vdas)mentioning

confidence: 99%

Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches

Choi

Armaiz-Pena

Pradeep

et al. 2014

Cancer Metastasis Rev

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Resistance to chemotherapy is among the most important issues in the management of ovarian cancer. Unlike cancer cells, which are heterogeneous as a result of remarkable genetic instability, stromal cells are considered relatively homogeneous. Thus, targeting the tumor microenvironment is an attractive approach for cancer therapy. Arguably, anti-vascular endothelial growth factor (anti-VEGF) therapies hold great promise, but their efficacy has been modest, likely owing to redundant and complementary angiogenic pathways. Components of platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and other pathways may compensate for VEGF blockade and allow angiogenesis to occur despite anti-VEGF treatment. In addition, hypoxia induced by antiangiogenesis therapy modifies signaling pathways in tumor and stromal cells, which induces resistance to therapy. Because of tumor cell heterogeneity and angiogenic pathway redundancy, combining cytotoxic and targeted therapies or combining therapies targeting different pathways can potentially overcome resistance. Although targeted therapy is showing promise, much more work is needed to maximize its impact, including the discovery of new targets and identification of individuals most likely to benefit from such therapies.

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“…1,3,4) 42,87,88. The engineered design for SMSDTTS that combines sequential intravenous injection of CA4P and 131 I-Hyp at a 24h interval is believed advantageous for the following considerations: a) being both naturally derived small molecules allowing systemic injections with much better accessibility to targeted tissues, CA4P and Hyp (in the form of its radiolabeled iodo-derivative) share a highly targeting capacity but diverse and complementary specificities; b) massive intra-tumoral necrosis induced by CA4P serves as a target or anchor for 131 I-Hyp; c) a 24h interval between CA4P and 131 I-Hyp allows the complete formation of necrosis, meanwhile optimal accessibility to the latter due to partial recovery of tumor vascularization 89; d) iodine-131 that emits tumoricidal beta particles and gamma rays useful for scintigraphy provides a theragnostic solution for malignancies; e) being spatially or geographically cooperational, CA4P kills tumor cells inside out, whereas 131 I-Hyp eradicates the remnant tumor cells on the periphery. Micro-geographically, 131 I-Hyp accumulates with high concentration into the necrotic tissue neighboring the viable cancer cells.…”

Section: Engineered Designs With Smsdttsmentioning

confidence: 99%

Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications

Li¹,

Oyen²,

Verbruggen³

et al. 2013

J. Cancer

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Hitting the evasive tumor cells proves challenging in targeted cancer therapies. A general and unconventional anticancer approach namely small molecule sequential dual-targeting theragnostic strategy (SMSDTTS) has recently been introduced with the aims to target and debulk the tumor mass, wipe out the residual tumor cells, and meanwhile enable cancer detectability. This dual targeting approach works in two steps for systemic delivery of two naturally derived drugs. First, an anti-tubulin vascular disrupting agent, e.g., combretastatin A4 phosphate (CA4P), is injected to selectively cut off tumor blood supply and to cause massive necrosis, which nevertheless always leaves peripheral tumor residues. Secondly, a necrosis-avid radiopharmaceutical, namely 131I-hypericin (131I-Hyp), is administered the next day, which accumulates in intratumoral necrosis and irradiates the residual cancer cells with beta particles. Theoretically, this complementary targeted approach may biologically and radioactively ablate solid tumors and reduce the risk of local recurrence, remote metastases, and thus cancer mortality. Meanwhile, the emitted gamma rays facilitate radio-scintigraphy to detect tumors and follow up the therapy, hence a simultaneous theragnostic approach. SMSDTTS has now shown promise from multicenter animal experiments and may demonstrate unique anticancer efficacy in upcoming preliminary clinical trials. In this short review article, information about the two involved agents, the rationale of SMSDTTS, its preclinical antitumor efficacy, multifocal targetability, simultaneous theragnostic property, and toxicities of the dose regimens are summarized. Meanwhile, possible drawbacks, practical challenges and future improvement with SMSDTTS are discussed, which hopefully may help to push forward this strategy from preclinical experiments towards possible clinical applications.

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Influence of the vascular damaging agents DMXAA and ZD6126 on hypericin distribution and accumulation in RIF-1 tumors

Cited by 13 publications

References 27 publications

Vascular priming enhances chemotherapeutic efficacy against head and neck cancer

Vascular priming enhances chemotherapeutic efficacy against head and neck cancer

Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches

Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications

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