Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity.

By G. Klement, P. Bőhlen, R. Kerbel. Journal of Clinical Investigation, 2000

753 citations recorded by the source corpus.

Subfields: Neurology, Pulmonary and Respiratory Medicine, Radiation

View Paper: https://www.semanticscholar.org/paper/f71a8431a4e20a2227fc213bcd7051f01a556707

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Neurology

1. N. Ferrara
2. D. Hanahan
3. J. Folkman
4. G. Bergers
5. B. Kamen
6. R. Kerbel
7. J. Joyce
8. M. Shibuya

In Pulmonary and Respiratory Medicine

1. N. Ferrara
2. H. Gerber
3. J. Folkman
4. B. Kamen
5. D. Hanahan
6. R. Kerbel
7. Y. Luqmani

In Radiation

1. J. Folkman
2. B. Kamen
3. N. Ferrara
4. R. Kerbel

Citations in the corpus

• Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor (2002, result): “This observation is consistent with the low-dose, delayed effects on tumors typically seen with other reported antiangiogenic treatment protocol”
• Ten years of anti-vascular endothelial growth factor therapy (2016, background): “…was to simultaneously target the endothelial cells and the tumour cells, and, indeed, preclinical studies confirmed a synergistic effect between bevacizumab and cytotoxic therapies, in part because VEGFA blockade seems to sensitize the endothelium to the effects of the cytotoxic agents 73–75 .”
• Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). (2008, background): “In preclinical experiments, sustained VEGF inhibition has been shown to achieve and maintain tumor regression.(6,7) However, the clinical benefit and risks associated with continued bevacizumab use after initial progressive disease are currently unknown.”
• Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. (2000, background): “(5) also explored the use of the mAb DC-101 (6), which disrupts the function of VEGF-R2/flk-1/KDR, one of two receptors for VEGF.”
• Vascular Endothelial Growth Factor and Angiogenesis (2004, background): “They concluded that the blockade of VEGF function may render surviving endothelial cells more vulnerable to chemotherapy, especially if given at low doses, by the possible down-regulation of multiple antiapoptotic proteins normally induced by VEGF (Klement et al., 2000).”
• The biology of VEGF and its receptors (2003, background): “Several studies have shown that combining anti-VEGF treatments with chemotherap”
• Mechanisms of Drug Resistance in Cancer Chemotherapy (2005, background): “Experiments in tumour-bearing mice have shown that administration of DC101, a blocker of vascular endothelial growth factor, and a submaximal tolerated dose of vinblastine induced effective tumour regression. Given individually, both agents were ineffective [”
• The anti-angiogenic basis of metronomic chemotherapy (2004, methodology): “The results of Browder et al. and Klement et al. have now been confirmed by many different groups using various empirical continuous or frequent low-dose chemotherapy regimens.”
• Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer (2004, background): “The carboxyl-terminal domain (111-165) of vascular endothelial growth factor is critical for its mitogenic potency.”
• Opinion: Angiogenesis: an organizing principle for drug discovery? (2007, result): “confirmed this approach with a different chemotherapeutic agen”