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DRUG CLASS:

IGF-1R-targeted antibody-drug conjugate

Related drugs:
1year
Simultaneous spatial evaluation of IDH1, EGFR, IGF1R and Ki67 biomarkers in glioblastoma (Neuroscience 2023)
We applied a spatial biology methodology for co-detection of multiple GBM biomarkers which allowed us to analyze their spatial distribution as well as the extent of colocalization at the single-cell level. Co-detection of multiple biomarkers has a strong diagnostic potential especially when analyzing limited small-size biopsies.
EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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EGFR positive
1year
Phase I trial of ganitumab plus dasatinib to cotarget the insulin-like growth factor 1 receptor and Src family kinase YES in rhabdomyosarcoma. (PubMed, Clin Cancer Res)
The combination of dasatinib 60 mg/m2/dose daily and ganitumab 18 mg/kg every two weeks was safe and tolerable. This combination had a disease control rate of 22% at five months.
P1 data • Journal
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dasatinib • ganitumab (AMG 479)
1year
Thyroid cancers exhibit oncogene-enhanced macropinocytosis that is restrained by IGF1R and promotes albumin-drug-conjugate response. (PubMed, Clin Cancer Res)
These findings identify regulated oncogene-driven macropinocytosis in thyroid cancers and demonstrate the potential of designing albumin-bound drugs to efficiently treat them.
Journal
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BRAF (B-raf proto-oncogene) • PTEN (Phosphatase and tensin homolog) • IGF1 (Insulin-like growth factor 1)
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BRAF V600E • BRAF V600 • RAS mutation
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metformin
over1year
Redundant Signaling as the Predominant mechanism for Resistance to Antibodies Targeting IGF-1R in Cells Derived from Childhood Sarcoma. (PubMed, Mol Cancer Ther)
The BRD4 inhibitor, JQ1, was evaluated as an agent to prevent acquired TZ-1 resistance in Rh41 cells...Acquired resistance in Rh41 cells, is associated with rapid induction of multiple RTKs indicating a dynamic response to IGF-1R blockade and rapid development of resistance. The TZ-1 antibody had greater antitumor activity against Rh41 xenografts compared to other IGF-1R-targeted antibodies tested against this model.
Journal
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BRD4 (Bromodomain Containing 4)
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JQ-1
over2years
Targeted siRNA nanocarrier: a platform technology for cancer treatment. (PubMed, Oncogene)
Using these nanoparticles, EWS/FLI1 knockdown blocked in vitro and in vivo growth of Ewing sarcoma cells. We conclude that these antibody-protamine-siRNA nanocarriers provide a novel platform technology to specifically target different cell types and yet undruggable targets in cancer therapy by RNAi.
Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • EWSR1 (EWS RNA Binding Protein 1) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)
over2years
Molecular Mechanisms, Biomarkers and Emerging Therapies for Chemotherapy Resistant TNBC. (PubMed, Int J Mol Sci)
Recently, based on specific biomarkers, some therapies were tailored to TNBC subsets and became available in clinical practice: olaparib and talazoparib for BRCA1/2 germline mutation carriers larotrectinib and entrectinib for neurotrophic tropomyosin receptor kinase (NTRK) gene fusion carriers, and anti-trophoblast cell surface antigen 2 (Trop2) antibody drug conjugate therapy for heavily pretreated metastatic TNBC (mTNBC). Among them, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and EGFR inhibitors as well as antiandrogens showed promising results and are under evaluation in Phase II/III clinical trials. Emerging therapies allow to select specific antiblastics that alone or by integrating the conventional therapeutic approach may overcome/hinder chemoresistance.
Review • Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • mTOR (Mechanistic target of rapamycin kinase) • IGF1 (Insulin-like growth factor 1) • NTRK (Neurotrophic receptor tyrosine kinase) • ADAM10 (ADAM Metallopeptidase Domain 10)
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Lynparza (olaparib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Talzenna (talazoparib)
almost3years
Immunotherapy and Radioimmunotherapy for Desmoplastic Small Round Cell Tumor. (PubMed, Front Oncol)
Successful treatment with immunotherapy or radioimmunotherapy following debulking surgery could eradiate these micrometasteses and prevent relapse. Although there has been limited success to date for immunotherapy in pediatric solid tumors, the significant improvements in survival seen in the treatment of other pediatric solid tumors, such as metastatic neuroblastoma and its CNS spread, suggest a potential of immunotherapy and specifically compartmental immunotherapy in DSRCT.
Review • Journal
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PDGFA (Platelet Derived Growth Factor Subunit A)
3years
Results of TRIO-14, a phase II, multicenter, randomized, placebo-controlled trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-ganitumab in newly diagnosed epithelial ovarian cancer. (PubMed, Gynecol Oncol)
Addition of ganitumab to CP chemotherapy in primary EOC did not improve PFS. Our results do not support further study of ganitumab in unselected EOC patients.
Clinical • P2 data • Journal
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IGFBP2 (Insulin-like growth factor binding protein 2)
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carboplatin • paclitaxel • ganitumab (AMG 479)
over4years
111In and 225Ac-labeled cixutumumab for imaging and alpha particle radiotherapy of IGF-1R positive triple negative breast cancer. (PubMed, Mol Pharm)
Additionally, low specific activity radioimmunoconjugate led to complete tumor remission in 2/6 mice. The data suggest that efficacy of cixutumumab can be enhanced by radiolabeling with 225Ac at a low specific activity.
Journal
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IGF1R (Insulin-like growth factor 1 receptor)
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IGF1R overexpression
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cixutumumab (IMC A12)
over4years
IGF-1R/mTOR Targeted Therapy for Ewing Sarcoma: A Meta-Analysis of Five IGF-1R-Related Trials Matched to Proteomic and Radiologic Predictive Biomarkers. (PubMed, Cancers (Basel))
Reduced total-lesion glycolysis more accurately predicted the IGF-1R response than other previously reported radiological biomarkers. Synergistic drug combinations, and newly identified proteomic or radiological biomarkers of IGF-1R response, may be incorporated into future IGF-1R-related trials to improve the response rate in ES patients.
Retrospective data • Journal
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IGF1R (Insulin-like growth factor 1 receptor) • IGF1 (Insulin-like growth factor 1)