Potential therapeutic targets in renal cell carcinoma PDF Print E-mail

Drug Testing Approaches

Introduction

Protein-kinases are attractive targets for anti-neoplastic therapy in a wide spectrum of tumors. The research team is specialized in study of renal cell carcinoma (RCC) which accounts for 2-3% of all malignant diseases in adults in Europe.

A major challenge in designing new kinase inhibitors is to determine which kinases to inhibit to maximize efficacy and therapeutic index.


Thus, defining the essential «kinome» in individual cancers represents a new approach to identify new clinical biomarkers and to design efficacious multitargeted kinase inhibitors. In this context, characterization of the kinome events unique to CRC could be of critical significance for future innovative therapies.
Based on Grenoble team know-how in the protein kinase field together with a facilitated access to functional genomic and chemogenomic platforms, researchers should provide you with new avenues to uncover novel therapeutic targets, thus accelerating oncology drug development.

1) Characterization of your new drug with a complete approach

  • We propose you to evaluate your drug activity and/or toxicity on various cancer cell lines and to analyze their cellular effects on cell cultures or cocultures.
  • In follow-up studies/ from these results, kinases perturbed by these drugs could be studied.
2) Kinase loss-of-function RNAi screen
  • We propose you to identify kinase requirements for renal carcinoma cells grown on cell lines using a commercial panel of RNAi directed to all human kinases or lentivirus transduction method

Key Benefits
The possibility of finding specific kinase signatures in a rapid and reliable manner is a powerful approach.
Proof of concept will be to look whether the effects of the RNAi observed in vitro would translate in vivo into altered
tumour development.
This approach will help to distinguish those kinases that are the drivers of tumor progression from those that are
passengers in the process.

3) Defining of the identified hits as potential clinical biomarkers and/or new drug targets

3.1 Clinical biomarkers
To categorize renal tumours at diagnosis into distinct molecular subtypes, we will determine whether the identified survival kinases could represent pathwayspecific biomarkers clinically usefull in the diagnostic and the prognostic of this disease.

Key benefits
The challenge is that discovery of a biomarker and clinical testing of a drug active on it, are often interdependent
and should ideally move forward in parallel.

3.2 Drug targets
We will determine whether the targets identified in the RNAi screens may represent bona-fide cancer targets in themselves and will focus on the identification of small molecule inhibitors of kinases characterized as essential for renal cancer cell survival.

Key features
Expertise of the researcher's team in the development of new CK2 inhibitors and in the use of multidisciplinary tools

> Fields of application
> Drug discovery
> Drug development
> Oncology
> Diagnosis

Commercial Opportunities
We are currently searching for industrial partners interested in licensing or co-developement

Contact
Nicole Giraud
+33 (0)4 76 00 78 42
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