Renal Cell Carcinoma PDX Models

XenTech has built up a new panel of renal patient-derived tumor xenograft (PDX) models for the evaluation of new therapies for renal cell carcinoma (RCC), the most common and lethal of all kidney cancers.

RCC, also called kidney cancer or renal adenocarcinoma originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that transport glomerular filtrate from the glomerulus to the descending limb of the nephron. RCC accounts for approximately three per cent of adult malignancies and 90-95 per cent of neoplasms arising from the kidney. RCCs are highly heterogeneous; clinically, morphologically and cytogenetically.

Xentech’s laboratory RCC Xenografts are established by obtaining primary renal tumors and RCC metastases from surgical resection patients and subcutaneously engrafting them into immune deficient mice.

XenTech has thus built up an RCC PDX panel comprising primary tumors and metastases, and two major subtypes of RCC:

Clear cell and/or granular RCC: This form is the most common histologic variant accounting for 70% of all RCCs. Microscopically, clear cell RCCs are composed of cells with abundant clear cytoplasm surrounded by a distinct cell membrane. The alveolar architecture is created by thin-walled vascular septa in which acinar or papillary areas may be observed.

Papillary RCC: The papillary subtype of RCC represents 10% of all adult kidney tumors. Histologically, it is composed of 80% or more of papillary or tubulopapillary structures characterized by a single layer of small cuboidal cells with basophilic cytoplasm.

Applications
A panel of RCC PDXs, including the major subtypes of RCC represents an opportunity for drug developers to validate the anti-cancer efficacy of their drug candidates in translational and highly relevant pre-clinical models.

Despite recent advances in the treatment of RCC, unmet needs persist that are potentially addressed by Xentech PDX models.

These include:
Clear cell RCC: Although targeted therapies are currently approved for use in clear cell RCC (CCRCC) and have shown improvements in overall survival and progression-free survival, the prognosis of advanced CCRCC remains poor and life expectancy for those patients is low. One of the biggest limits to these approved therapies is drug resistance. RCC PDXs offer enhanced possibilities of:

• Studying such resistance and strategies to circumvent it
• Evaluating any synergistic effect of combination therapies
• Identifying new targets

Papillary RCC: The unmet medical needs are even more pressing, regarding papillary RCC (PRCC). The few existing data using VEGFR inhibitors in PRCC have been disappointing and underscore the need to develop more effective therapies.

For more information on Renal Cell Carcinoma PDX Models, please contact Xentech directly.