Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma

Helfrich, Iris; Scheffrahn, Inka; Bartling, Sönke; Weis, Joachim; Felbert, Verena von; Middleton, Mark R.; Kato, Masahi; Ergün, Süleyman; Augustin, Hellmut G.; Schadendorf, Dirk

doi:10.1084/jem.20091846

Cited by 166 publications

(96 citation statements)

References 56 publications

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“…Surviving blood vessels of RIP-Tag-2 tumors treated with anti-VEGF agents have a reduced expression of VEGFR-2 and VEGFR-3 in addition to a more normal caliber [29]. More recently, Helfrich et al [33] demonstrated in spontaneoulsy developing melanomas of MT/ret transgenic mice after using anti-VEGF therapy and in human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment with bevacizumab, that tumor vessels which are resistant to anti-VEGF therapy are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes.…”

Section: Vascular Normalization Increases Pericyte Coveragementioning

confidence: 99%

Vascular normalization: a real benefit?

Ribatti

2011

Cancer Chemother Pharmacol

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Abstract. It is well established that antibodies to vascular endothelial growth factor (VEGF) in combination with chemotherapeutic agents produce synergistic cytotoxicity in a range of cancer. In this review article it has been analyzed if the so called "vascular normalization" of abnormal tumor blood vessels as an effect of VEGF inhibition in association with chemotherapeutic agents in the treatment of tumors, produces a real benefit. Literature data show that the process of normalization of the structure of tumor blood vessels is not always accompained with a real benefit. In fact as in the case of cerebral tumors, the process of normalization may induce a re-establishment of the low permeability characteristics of normal brain microvasculature, preventing the delivery of chemotherapeutics.

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Section: Vascular Normalization Increases Pericyte Coveragementioning

confidence: 99%

Vascular normalization: a real benefit?

Ribatti

2011

Cancer Chemother Pharmacol

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“…[42] This angiogenic switch of the tumor vasculature makes it more resistant to antiangiogenic agents or radiation therapy since the vessels become mature, rigid, and less vulnerable to VEGF inhibition. [43][44][45] Thus, optimal doses and schedule of these antiangiogenic drugs designed according to the angiogenic profile of tumors can normalize tumor vasculature and its microenvironment without causing harm to the normal tissues. Here, we have shown antiangiogenic therapy is an attractive option to overcome tumor hypoxia and radioresistance.…”

Section: Resultsmentioning

confidence: 99%

Vascular normalization window: A positive prognostic foresight for head and neck cancer

Asha¹,

Dua²,

Rajarathnam³

et al. 2015

JCRI

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Tumor angiogenesis is a hallmark of advanced cancers which is critical for the continued growth and progression of solid tumors owing to the metastatic spread of tumor cells. This knowledge has led to the concept of targeting the tumor vasculature as a therapeutic modality. Several retrospective studies support the positive prognosis for the implications of angiogenic markers for head and neck squamous cell carcinoma (HNSCC), currently making them an attractive target oriented treatment. Radiotherapy (RT) being the conventional treatment for HNSCC, makes it imperative in this present era to recognize the communication between antiangiogenic therapy and RT, thus developing a combination therapy to achieve progress in the outcome of clinical practice. The combination of antiangiogenic agents and ionizing radiation involve many interactions between the cells, the stroma of the tumor and tissue vasculature. Increased angiogenesis is responsible for the proliferation of tumor cells and its metastasis which ultimately leads to tumor hypoxia. Any agent targeting the tumor vasculature can modulate the tumor microenvironment thus normalizing it and enhancing the therapeutic response of hypoxic cells of head and neck cancers. This review provides insight into the mechanisms by which the antiangiogenic therapy combined with RT improves the tumor response to radiation, thereby suggesting a promising prognostic treatment modality of HNSCC in the time ahead.

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“…Thus, encouraging results have been obtained in selected advanced pNETs, however, in other cases, the responses were short in duration or the disease was clearly resistant. The explanation can be partially found in an important preclinical study; the VEGF-targeted molecules suppress the growth of new vessels, but the action against stable tumor vasculature was much less intense (34). Furthermore, in early phases of cancer progression, the tumor's new blood vessels are more dependent on the VEGF pathway, a dependency, however, that, in later phases, is reduced or completely lost, thus leaving space to other angiogenic drivers to gain the scene (35).…”

Section: Angiogenesis Inhibitors To Treat Pnetsmentioning

confidence: 99%

Antiangiogenic Therapy in Pancreatic Neuroendocrine Tumors

Capozzi

Arx

Divitiis

et al. 2016

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Abstract. In recent years, many progresses have been pursued in the management of advanced pancreatic neuroendocrine tumor (pNET); most of them were prompted by increasing knowledge of biology of these neoplasms, including the identification of promisingEpidemiological studies showed that pancreatic neuroendocrine tumors (pNETs) are rare cancers with an incidence of less than 1 per 100,000 persons per year, representing 1-2% of all pancreatic neoplasms in Europe (1). However, in recent years, an increase of pNETs' incidence has been registered probably because of a better identification of these tumors due to the improvement of pathologic and diagnostic techniques (2). It is fundamental, in order to indicate the most appropriate therapy, a clear identification of the pNETs' origin, grading, as well as presence and localization of metastases. To date, this is possible by acquiring data from laboratory tests, histology and radiologic imaging (3, 4). Biopsy of the tumor is the first fundamental step to achieve an appropriate diagnosis and classification of pNET, including immunocytochemical staining to determine eventual secretion of substances ("secreting" pNETs). Thus, the first important discrimination is between well-differentiated (low or intermediate grade) or poorly differentiated (high-grade) tumors (6).On a clinical point of view, some types of pNETs are asymptomatic and indolent and may grow at a very low rate for several years before displaying symptoms; other types can rapidly progress determining disability and worsening of quality of life (7).If the tumor is identified in early, localized stage, radical surgery is the gold standard treatment (8). Unfortunately, hepatic 5025 This article is freely accessible online.

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Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma

Cited by 166 publications

References 56 publications

Vascular normalization: a real benefit?

Vascular normalization: a real benefit?

Vascular normalization window: A positive prognostic foresight for head and neck cancer

Antiangiogenic Therapy in Pancreatic Neuroendocrine Tumors

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