Abstract
Tyrosine kinase receptors and their ligands have become appealing candidates as molecular therapeutic agents for the treatment of cancer. Hepatocyte growth factor (HGF) and its receptor, mesenchymal-epithelial transition factor (c-Met), play a role in many human tumors, promoting cell proliferation and invasion, as well as resistance to apoptosis. Rilotumumab, being developed by Amgen Inc, is a humanized mAb directed against HGF, and is thus able to interfere with the interaction between HGF and c-Met to prevent c-Met activation. In preclinical studies, rilotumumab effectively blocked c-Met phosphorylation, inhibiting c-Met-activated downstream signaling pathways. In phase I clinical trials, rilotumumab was well tolerated at doses up to 20 mg/kg every 2 weeks. Data from preclinical studies and a phase Ib trial demonstrated that rilotumumab had an additive effect when combined with chemotherapeutic agents, leading to the initiation of several phase II trials that are enrolling patients with different tumor types to assess combinations of rilotumumab with chemotherapeutic regimens, as well as with other mAbs. Which tumor types might beneft most from treatment with rilotumumab remains to be determined, and the identifcation of candidate patients will be a critical issue for the further development of this drug.
| Original language | English |
|---|---|
| Pages (from-to) | 448-455 |
| Number of pages | 8 |
| Journal | Current Opinion in Molecular Therapeutics |
| Volume | 11 |
| Issue number | 4 |
| Publication status | Published - Aug 2009 |
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ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Molecular Medicine
- Genetics(clinical)
- Drug Discovery
- Pharmacology
Cite this
Rilotumumab, a mab against human Hepatocyte growth factor for the treatment of cancer. / Giordano, Silvia.
In: Current Opinion in Molecular Therapeutics, Vol. 11, No. 4, 08.2009, p. 448-455.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rilotumumab, a mab against human Hepatocyte growth factor for the treatment of cancer
AU - Giordano, Silvia
PY - 2009/8
Y1 - 2009/8
N2 - Tyrosine kinase receptors and their ligands have become appealing candidates as molecular therapeutic agents for the treatment of cancer. Hepatocyte growth factor (HGF) and its receptor, mesenchymal-epithelial transition factor (c-Met), play a role in many human tumors, promoting cell proliferation and invasion, as well as resistance to apoptosis. Rilotumumab, being developed by Amgen Inc, is a humanized mAb directed against HGF, and is thus able to interfere with the interaction between HGF and c-Met to prevent c-Met activation. In preclinical studies, rilotumumab effectively blocked c-Met phosphorylation, inhibiting c-Met-activated downstream signaling pathways. In phase I clinical trials, rilotumumab was well tolerated at doses up to 20 mg/kg every 2 weeks. Data from preclinical studies and a phase Ib trial demonstrated that rilotumumab had an additive effect when combined with chemotherapeutic agents, leading to the initiation of several phase II trials that are enrolling patients with different tumor types to assess combinations of rilotumumab with chemotherapeutic regimens, as well as with other mAbs. Which tumor types might beneft most from treatment with rilotumumab remains to be determined, and the identifcation of candidate patients will be a critical issue for the further development of this drug.
AB - Tyrosine kinase receptors and their ligands have become appealing candidates as molecular therapeutic agents for the treatment of cancer. Hepatocyte growth factor (HGF) and its receptor, mesenchymal-epithelial transition factor (c-Met), play a role in many human tumors, promoting cell proliferation and invasion, as well as resistance to apoptosis. Rilotumumab, being developed by Amgen Inc, is a humanized mAb directed against HGF, and is thus able to interfere with the interaction between HGF and c-Met to prevent c-Met activation. In preclinical studies, rilotumumab effectively blocked c-Met phosphorylation, inhibiting c-Met-activated downstream signaling pathways. In phase I clinical trials, rilotumumab was well tolerated at doses up to 20 mg/kg every 2 weeks. Data from preclinical studies and a phase Ib trial demonstrated that rilotumumab had an additive effect when combined with chemotherapeutic agents, leading to the initiation of several phase II trials that are enrolling patients with different tumor types to assess combinations of rilotumumab with chemotherapeutic regimens, as well as with other mAbs. Which tumor types might beneft most from treatment with rilotumumab remains to be determined, and the identifcation of candidate patients will be a critical issue for the further development of this drug.
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M3 - Article
C2 - 19649990
AN - SCOPUS:68649091709
VL - 11
SP - 448
EP - 455
JO - Current Opinion in Molecular Therapeutics
JF - Current Opinion in Molecular Therapeutics
SN - 1464-8431
IS - 4
ER -