Bladder cancer diagnostics
Bladder cancer is the fourth most frequent bladder cancer in men and the ninth in women. Patients with superficial tumors (75%) display recurrence in 70% of cases over the years, but progression toward muscle invasion happens in 10-20% of cases. Bladder tumors that display muscle invasion at the time of diagnosis (20%) have a much less favourable prognosis and often progress rapidly.
Diagnosis and classification of a bladder tumor is crucial for the application of the most suitable treatment. In the case of invasive tumors, the bladder must be removed, with lymphadenectomy and bladder reconstruction, whereas superficial tumors can be removed by means of a transurethral excision, preserving the bladder, and treated by means of chemotherapy or intravesical immunotherapy. The final bladder cancer diagnosis is currently made by means of the analysis of bladder tissue extracted by cistoscopy. In this analysis, the tumor stage can also be determined in a non-specific manner, as so far there are no molecular markets to facilitate the classification.
FGFR3 is a receptor of fibroblast growth factors, which has a protein kinase intracellular domain, and is involved in the regulation of cell proliferation, differentiation, and apoptosis.
Several FGFR3 mutations have been described in melanoma, cervix cancer, and multiple myeloma. These mutations seem to activate the receptor, which leads to an oncogenic effect. Even though some receptor mutations have also been found in bladder tumors, the most common FGFR3 disorder in this pathology is overexpression of mutated and native protein.
FGFR3 overexpression in the bladder happens most frequently in superficial tumors, which have not invaded the lamina propria and can be easily excised. Thus, detection of FGFR3 in bladder carcinomas makes it possible to differentiate them from healthy tissue and determine the tumor stage, distinguishing between Ta and T1 tumors, which are non-invasive and easy to excise, from T2 tumors, which require a more aggressive treatment.
FGFR3 has also been described as a valid therapeutic target for the treatment of several types of tumors. There are several drugs under development that are based on the inhibition of this receptor to halt tumor development.
DMTX bladderScan is an immunohistochemistry assay, based on a monoclonal antibody that specifically detects FGFR3 in tissue biopsy samples from patients with superficial bladder carcinomas.
- DMTX bladderScan is based on an Oncomatryx proprietary monoclonal antibody that specifically detects the extracellular domain of FGFR3
- DMTX bladderScan antibody does not crossreact with other FGFRs, as it has been tested by immunocytochemistry on different cell lines
- DMTXbladderScan is more sensitive and more cuantitative than the most commonly used commercial antibody.
- DMTX bladderScan is suitable for the diagnosis of bladder cancer in tissues by means of IHC, as well as to determine tumor invasiveness, differentiating Ta and T1 stages from invasive T2.
- DMTX bladderScan is particularly sensitive in the detection of superficial bladder carcinomas, which are harder to diagnose using current techniques.
- Detection of FGFR3 in tissue by means of DMTX bladderScan is useful to select patients who can be treated using anti-tumor therapies targeting FGFR3.
Targeting the extracellular domain of fibroblast growth factor receptor 3 with human single-chain Fv antibodies inhibits bladder carcinoma cell line proliferation. Martínez-Torrecuadrada JM. et al. Clinical Cancer Research 2005; 11(17):6280-90
Fibroblast growth factor receptor 3 is overexpressed in urinary tract carcinomas and modulates the neoplastic cell growth. Gómez-Román J. et al. Clinical Cancer Research 2005; 11:459-465
Fibroblast growth factor receptor 3 is overexpressed in urinary tract carcinomas and modulates the neoplastic cell growth. Gomez-Roman, J, Clin Cancer Res 2005;11:459-465
Targeting the extracellular domain of fibroblast growth factor receptor 3 with human single-chain Fv antibodies inhibits bladder carcinoma cell line proliferation. Martínez-Torrecuadrada et. al, Clin Can Res 2005; 11:6280-6290
FGFR3-targeted mAb therapy for bladder cancer and multiple myeloma. Hadari et al, J Clin Invest 2005; 119(5):1077-9
Frequency of fibroblast growth factor receptor 3 mutations in sporadic tumours. Sibley et al, Oncogene 2001; 20(32):4416-8
The incidence of thanatophoric dysplasia mutations in FGFR3 gene is higher in low-grade or superficial bladder carcinomas. Kimura et al, Cancer 2001; 92(10): 2555-61
The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Van Rhijn et al, Cancer Res 2001; 61(4):1265-8
Ectopic expression of fibroblast growth factor receptor 3 promotes myeloma cell proliferation and prevents apoptosis. Plowright EE et al, Blood 2000;95(3):992-8
Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. Chen L. et al, J Clin Invest 1999;104(11):1517-25