User:Achavez0921/Dalotuzumab
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Dalotuzumab is an anti-IGF1 receptor (IGF1R) humanized monoclonal antibody designed for the potential treatment of various cancers.[1] Common adverse effects include hyperglycemia, nausea, vomiting, and fatigue.[2] Dalotuzumab was developed by Merck and Co., Inc.[3]
Indications[edit]
Dalotuzumab is indicated to treat breast cancer, colorectal cancer, multiple myeloma, neuroendocrine tumors, non-small cell lung cancer (NSCLC), pancreatic cancer, and solid tumors.[1]
Adverse Effects[edit]
Adverse effects of Dalotuzumab:[1][2][4]
- Infusion-related reaction
- Fever
- Chills
- Fatigue
- Weakness
- Weight loss
- Nausea
- Vomiting
- Rash
- Stomatitis
- Abdominal pain
- Intestinal bleeding
- Constipation
- Diarrhea
- Hyperglycemia
- Transaminitis
- Neutropenia
- Thrombocytopenia
- Pneumonitis
Mechanism of Action[edit]
Insulin-like growth factors (IGFs) are pivotal in cellular processes contributing to normal physiology as well as certain pathologies (e.g., cancer).[3] The IGF family of proteins, also known as the IGF axis, consists of three ligands (insulin, IGF1, IGF2), three cell surface receptors (insulin receptor [IR], IGF1 receptor [IGF1R], IGF2 receptor [IGF2R]), and seven IGF binding proteins (IGFBP1-7).[5] Notably, IGF1R serves as the primary receptor within the IGF axis.[5] The IGF1R is a receptor tyrosine kinase (RTK) with a heterotetrameric structure composed of two extracellular α subunits and two transmembrane β subunits.[3][5] Upon ligand-induced activation of this receptor, cytoplasmic adaptor proteins, Src-homology collagen (Shc) and insulin receptor substrate (IRS), are phosphorylated and, in turn, trigger the activation of the Ras/Raf/MEK/Erk and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways, respectively.[3] These signaling pathways are involved in the regulation of cell survival and cell cycle progression.[3]
Furthermore, IGF1R amplification and overexpression has been observed in the formation of tumors and metastasis of various human cancers.[5] These findings justified the development of anti-IGF1R therapies with the goal of inhibiting aberrant receptor activity and potentially yielding anticancer effects.[3] Among said therapies, Dalotuzumab, a humanized monoclonal antibody, was designed to target and bind the extracellular domains of IGF1R, effectively blocking ligand activation of the receptor and preventing downstream signaling.[3] Moreover, the binding of Dalotuzumab to IGF1R, as seen with other anti-IGF1R antibodies, downregulates the expression of the receptors by prompting the internalization and degradation of IGF1R.[3]
History[edit]
There are now more than 30 different anti-IGF1R candidate drugs involved in over 70 industry and academic-initiated clinical trials.[6]
Dalotuzumab (MK-0646) was developed by Merck and Co., Inc. under license from French pharmaceutical company, Pierre Fabre.[3] Dalotuzumab presently remains in clinical trials and has not been granted FDA approval.[7]
References[edit]
- ^ a b c Scartozzi, Mario; Bianconi, Maristella; Maccaroni, Elena; Giampieri, Riccardo; Berardi, Rossana; Cascinu, Stefano (2010-06). "Dalotuzumab, a recombinant humanized mAb targeted against IGFR1 for the treatment of cancer". Current Opinion in Molecular Therapeutics. 12 (3): 361–371. ISSN 2040-3445. PMID 20521225.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Ma, Honghai; Zhang, Tiehong; Shen, Hongchang; Cao, Hongxin; Du, Jiajun (2014-06). "The adverse events profile of anti-IGF-1R monoclonal antibodies in cancer therapy". British Journal of Clinical Pharmacology. 77 (6): 917–928. doi:10.1111/bcp.12228. ISSN 1365-2125. PMC 4093917. PMID 24033707.
{{cite journal}}: Check date values in:|date=(help) - ^ a b c d e f g h i "Dalotuzumab Overview - Creative Biolabs". www.creativebiolabs.net. Retrieved 2023-01-01.
- ^ Gupta, Sameer; Engstrom, Paul F.; Cohen, Steven J. (2011-12). "Emerging therapies for advanced gastroenteropancreatic neuroendocrine tumors". Clinical Colorectal Cancer. 10 (4): 298–309. doi:10.1016/j.clcc.2011.06.006. ISSN 1938-0674. PMID 21813338.
{{cite journal}}: Check date values in:|date=(help) - ^ a b c d Wang, Panpan; Mak, Victor CY.; Cheung, Lydia WT. (2022-03). "Drugging IGF-1R in cancer: New insights and emerging opportunities". Genes & Diseases. doi:10.1016/j.gendis.2022.03.002. ISSN 2352-3042.
{{cite journal}}: Check date values in:|date=(help) - ^ Gombos, Andrea; Metzger-Filho, Otto; Dal Lago, Lissandra; Awada-Hussein, Ahmad (2012-03-14). "Clinical development of insulin-like growth factor receptor—1 (IGF-1R) inhibitors: At the crossroad?". Investigational New Drugs. 30 (6): 2433–2442. doi:10.1007/s10637-012-9811-0. ISSN 0167-6997.
- ^ "SEER*Rx Interactive Antineoplastic Drugs Database". SEER. Retrieved 2023-01-01.