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Novel Biomarker Proteins for CLL and Lung Cancer: Impact on Diagnosis, Prognosis, and Treatment

Introduction

 

The ability to accurately predict tumor behavior and thus patient survival represents a major clinical challenge for the effective management of cancer. Human tumors are riddled with genomic mutation that disrupt a wide spectrum of genes, but also affect protein expression levels. These alterations can be identified at the mRNA level, but most significantly at the protein expression level. A key challenge is identifying these alterations in differential protein expression as biomarkers enabling early diagnosis as well as to forecast cancer development, treatment efficacy and potentially giddiness of personal medicine.

 

The Technology

 

Using patient-derived samples, several dozens of proteins with 2-1000-fold change in their cancer vs. normal expression were identified in chronic lymphocytic leukemia (CLL) blood samples, adenocarcinoma (AC) lung cancer and squamous cell carcinoma (SCC). Some of these differentially displayed proteins enabled us to distinguish between patients in a stable disease state and those who would later be transferred to anti-cancer treatments or died of cancer (2-3 years before the physician decision). Down-regulation of expression of two of these proteins resulted in cell growth inhibition and can serve as new targets. In lung cancer, several novel biomarkers that enabled us to distinguish between AC and SCC have been identified, allowing for precise diagnosis, essential for selecting the appropriate treatment and thus increasing a patient’s life expectancy. These protein expression profiles can serve for diagnosing cancer, predicting cancer development and selecting and monitoring response to treatment.

 

Potential Applications

 

The newly identified biomarkers can be used to develop an antibodies-based commercial “kit” composed of a panel of these proteins for the following uses:

  • Blood tests for early diagnosis, selection and monitoring of treatment in CLL patients. In particular, predicting the disease progression 2-3 years in advance and thus enabling selecting patients that should start treatment
  • A panel of biomarkers to distinguish between AC or SCC lung cancer subtypes, allowing for more precise diagnosis of AC and SCC
  • Solid tumor biopsy profiling for diagnosis and for selecting and monitoring treatment in various cancers, including lung, ovary, prostate, glioblastoma and cervix cancer and melanomas

 

Patent Status

 

PCT patent application No. PCT/IL2016/051354 filed December 19, 2016
National Phase entry in: Israel, Europe and USA
PCT patent application No. PCT/IL2018/050554 filed on May 22, 2018
National Phase entry in: Israel, China, Europe and USA

 

Principal Investigator

 

Prof. Varda Shoshan-Barmatz, NIBN and the Department of Life Sciences, Ben-Gurion University of the Negev, Israel