Background
Renal cell carcinoma
Group of drug | Drugs | Ref. |
---|---|---|
cytokines | 1) Interleukin 2 - overall response rate - 15 %, complete response rate - 5 %, achieved by high dose. Problems with selection of patients who may benefit from treatment. 2) Interferon alfa - inferior to most new agents considering PFS (progression free survival), except in combination with bevacizumab. | |
VEGF-targeted drugs | 1) Sorafenib – second and subsequent lines of treatment. 2) Sunitinib – first line treatment for metastatic RCC. 3) Pazopanib – non-inferior to sunitinib 4) Axitinib – treatment refractory RCC. 5) Bevacizumab – used with interferon alfa. Superior PFS when compared with monotherapy of interferon alfa. | |
mTOR inhibitors | 1) Temsirolimus – for patient with poor risk as a first line druga
2) Everolimus – used as a second line or third line drug. |
General IGF-1 function
Circulation of IGF-1
IGF-1 receptor and insulin receptor homology
Molecular deregulation of IGF1R pathway and cancerogenesis
SNP/mutation | Nucleotide change | Type of cancer | Fuctional feature | Ref. |
---|---|---|---|---|
rs8038415 | TT | Breast cancer |
BRCA1 carriers with homozigosity TT at this SNP site experience a 40 % higher risk of breast cancer. | [103] |
rs2272037 | T > C | Colorectal cancer; Glioma | Significantly related with shorter OS in patients with metastatic colorectal cancer (mCRC). CT and TT associated with increased risk for glioma. | |
rs2016347 | G > T | Colorectal cancer, glioma | Related to reduced responsiveness to cetuximab treatment. Shorter OS in patients with mCRC. G allele associated with increased risk for Glioma (3’UTR in 3129 site) | |
rs8038415 | C/T | Non–small cell lung cancer (NSCLC) | Homozygous TT in this SNP had a significantly better OS compared with heterozygous individuals and a trend toward improved survival compared with patients that were homozygous for CC . | [106] |
CNV in IGF1R gene | Non–small-cell lung cancers (NSCLC) | High IGF1R gene copy number harbors positive prognostic value in NSCLC | [107] | |
Amplification in 15q26 | High grade glioma | Unkown | [108] | |
Amplification in 15q25-26 | Alveolar Rhabdomyosarcoma | Related with the rearrangement of PAX7 gene | [109] | |
A1374V | Lung squamous cell carcinoma | Unknown; mutation occur in the C-terminal lobe of the kinase catalytic domain | [110] | |
Deletion S1278 | Renal clear cell carcinoma | Unknown; deletion occur in the C-terminal tail region of the receptor | [110] | |
M1255I | Lung adenocarcinoma | Unknown; mutation occur in in the C-terminal lobe of the kinase catalytic domain | [110] | |
G596V | Thymic carcinoma | Exonic, Missense | [111] | |
rs61740868 | C/T | Unknown | Unfavorable substitution Arg1216Cys; showed an increase in energy (less favorable change) in comparison with the native structure. | [112] |
rs45437300 | A/T | Unknown | Nonsense mutation | [112] |
rs2229765 | A/G | Unknown | Affect splicing regulation; to be associated with higher plasma concentrations of circulating IGF1R | [112] |
rs55895813; rs36108138; rs45495500 | A/G; A/C; C/T | Unknown | Splicing site | [112] |