Renal Pelvic Transitional Cell Carcinoma (TCC) is a type of urothelial carcinoma that has a high level of aggression and is quite rare. Protheragen is dedicated to advancing the field of renal pelvis TCC diagnostics and therapeutics. We offer a wide range of services, including advanced imaging, histopathological analysis, molecular diagnostics, and preclinical research.
Overview of Renal Pelvis Transitional Cell Carcinoma (TCC)
Renal Pelvis Transitional Cell Carcinoma (TCC) is an uncommon but highly aggressive cancer that forms from the region of the upper urinary tract known as the renal pelvis, which is lined by transitional epithelium. Often considered a variant of upper tract urothelial carcinoma (UTUC), its natural history is somewhat erratic, and it is highly metastatic and recurrent. Even though it is uncommon, Renal Pelvis TCC is encountered quite late in its course, which significantly diminishes the prognosis and therapeutic options, presenting a major clinical hurdle. In cancer therapeutic modalities, preclinical studies are of paramount importance as they help to identify and evaluate new methods that will alter the clinical course of the disease.
Fig.1 Nomograms for predicting the 3-, 4-, and 5-year overall survival of patients with renal pelvic transitional cell carcinoma. (Hu T.,
et al., 2022)
Pathogenesis of Renal Pelvis TCC
The cause of renal pelvis TCC cancer is not purely one thing, as it stems from both genetic factors as well as environment. Studies have shown that there are mutations in the genes TP53, FGFR3, and TERT, which are known to cause the disease or advance it. Factors such as smoking or the use of some particular chemicals are known to contribute to the risk of contracting TCC. Moreover, persistent inflammation coupled with some genetic syndromes such as Birt-Hogg-Dubé syndrome, which is caused by a mutation in the FLCN gene, or Lynch syndrome, which is caused by mutations in the mismatch repair genes, has also been known to contribute to renal pelvis TCC.
Diagnostics Development for Renal Pelvis TCC
Urinary Cytology
Urinary cytology effectively aids in diagnosing upper tract urothelial carcinomas, such as Renal Pelvis TCC. Neoplastic cells may be detected in urine samples, which can be voided or collected via catheter. However, this method's sensitivity is quite limited, especially in low-grade TCC cases where cytology may overlook atypical cells. The sensitivity in identifying high-grade tumors is greater; thus, urinary cytology is especially useful in monitoring high-risk patients.
Biomarker Development
With advancements in molecular diagnostics, there has been a push to identify reliable biomarkers for the early detection and prognosis of Renal Pelvis TCC. Emerging research focuses on urinary biomarkers such as urinary bladder cancer antigen (UBC) and the nuclear matrix protein 22 (NMP22), which may improve diagnostic accuracy. Additionally, serum biomarkers like GDF-15 and hepcidin have been proposed as prognostic indicators, showing correlation with survival and metastasis in patients with upper tract urothelial carcinoma.
Therapeutics Development for Renal Pelvis TCC
- Chemotherapy
Chemotherapy remains the standard approach for advanced Renal Pelvis TCC, especially in patients with high-grade tumors or those with metastatic disease. Platinum-based regimens, such as cisplatin combined with gemcitabine, are commonly employed. While these therapies can be effective in managing the disease, they are often associated with significant side effects, necessitating the development of alternative therapeutics.
- Immunotherapy
Immunotherapy has shown promise in the therapeutic of upper tract urothelial carcinomas, including Renal Pelvis TCC. Immune checkpoint inhibitors like pembrolizumab and atezolizumab, which target PD-1 and PD-L1, have been evaluated in clinical trials. These therapies work by enhancing the body's immune response against cancer cells, offering a new avenue of therapy for patients who are refractory to traditional chemotherapy.
- Targeted Therapy
Targeted therapies that aim at specific molecular pathways are being explored to treat Renal Pelvis TCC. For instance, inhibitors of the PI3K-Akt-mTOR pathway are being tested in preclinical studies. Other promising agents include those targeting FGFR3 mutations, which are implicated in the development of urothelial carcinoma. These therapies are designed to interfere with the molecular mechanisms driving tumor growth, offering a more personalized therapy approach.
Table 1. Therapeutics of Renal Pelvis Transitional Cell Carcinoma.
| Therapeutics |
Drug Name |
Mechanism |
Description |
Stage |
| Chemotherapy |
Cisplatin-based regimens |
Inhibits DNA synthesis and repair, leading to cell death |
Used as adjuvant therapy to delay tumor recurrence and prolong survival |
Approved |
| Chemotherapy |
Gemcitabine |
Inhibits DNA synthesis by targeting DNA polymerase |
Often combined with cisplatin for systemic chemotherapy |
Approved |
| Immune Checkpoint Inhibitors (e.g., PD-1/PD-L1 inhibitors) |
NA |
Enhances the immune system's ability to recognize and attack cancer cells |
Used in advanced or recurrent cases to improve survival outcomes |
Preclinical |
| FGFR Inhibitors |
NA |
Targets the fibroblast growth factor receptor pathway, which is often mutated in TCC |
Investigated for patients with specific genetic mutations |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen provides a holistic approach to tackling Renal Pelvis Transitional Cell Carcinoma (TCC), encompassing both diagnostics and therapeutics. We specialize in the development of cutting-edge diagnostic tools that offer high sensitivity and specificity for early detection and disease monitoring. In parallel, our therapeutics development services are focused on creating novel small-molecule drugs, antibody-drug conjugates (ADCs), and gene therapies that target specific molecular vulnerabilities of Renal Pelvis Transitional Cell Carcinoma (TCC).
Disease Models
- UM-UC-14 CDX Models
- Renal Cell Carcinoma Organoids
- Pten Gene Knockout Mouse Models
- Rhesus Macaque (Macaca mulatta) Models
Recognizing that each drug development project is unique, Protheragen offers highly customized services tailored to the specific needs of our partners. We collaborate closely with our clients to design and execute research programs that align with their project goals and timelines. If you are interested in our services, please feel free to contact us.
References
- Hu, Tingting, and Shengjie You. "Overall and cancer-specific survival in patients with renal pelvic transitional cell carcinoma: a population-based study." Frontiers in Medicine 8 (2022): 719800.
- Jabbour, Teddy, et al. "Ipsilateral synchronous renal cell carcinoma and transitional cell carcinoma of the pelvicalyceal system."
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
