Dalotuzumab, a recombinant humanized mAb targeted against IGFR1 for the treatment of cancer.
Dalotuzumab (MK-0646; h7C10), being developed by Merck & Co Inc under license from Pierre Fabre SA, is a recombinant humanized IgG1 mAb against the IGFR1 for the potential intravenous treatment of cancer. Preclinical studies have demonstrated that dalotuzumab acts by inhibiting IGF-1- and IGF-2-mediated tumor cell proliferation, IGFR1 autophosphorylation and Akt phosphorylation. In multiple cancer cell lines and in mouse xenograft models, dalotuzumab displayed significant antitumor activity, in particular against NSCLC and breast cancer. In addition, coadministration of dalotuzumab with other anticancer agents, such as taxanes, enhanced the in vitro and in vivo antitumor activity of dalotuzumab. Preliminary data from phase I clinical trials suggest that dalotuzumab is safe, well tolerated and significantly inhibits tumor proliferation. At the time of publication, several clinical trials evaluating dalotuzumab, alone and in combination with other anticancer agents, were ongoing in patients with various types of solid tumor and in patients with multiple myeloma. Although preliminary results appear promising, only future clinical and translational data will clarify the best clinical setting and treatment combinations for the optimal use of dalotuzumab in clinical practice.
AO Ospedali Riuniti-Università Politecnica delle Marche, Clinica di Oncologia Medica, Via conca, 60020, Ancona, Italy. marioscartozzi@gmail.com
Mario
M
Scartozzi
Maristella
M
Bianconi
Elena
E
Maccaroni
Riccardo
R
Giampieri
Rossana
R
Berardi
Stefano
S
Cascinu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D007335:Insulin-Like Growth Factor II / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D009423:Nervous System Neoplasms / Q000188:drug therapy
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C569480:dalotuzumab