Laboratory results with the NPRL2 tumor suppressor gene demonstrated that infusions of NPRL2 nanoparticles in combination with cisplatin resulted in a 90 percent inhibition of tumor growth in human lung cancer cells compared to control treatments, reported Introgen Therapeutics, Inc. (Nasdaq: INGN – News).
A nanoparticle is human-made particle whose size is measured in microns or one-billionth of a meter. The NPRL2 gene is believed to be important in the development of multiple types of cancer, including lung cancer and renal cell cancer. It is licensed to Introgen by the University of Texas M. D. Anderson Cancer Center.
This study was performed in the laboratory of Dr. Lin Ji, associate professor in the Department of Thoracic and Cardiovascular Surgery at M. D. Anderson and collaborators in the Department of Imaging Physics at M. D. Anderson and The University of Texas Southwestern Medical Center.
Preclinical studies evaluated the NPRL2 gene which demonstrated its ability to exhibit tumor suppressor activity against human lung cancer. A study published in a recent issue of the biomedical journal Cancer Research indicated that low expression of the NPRL2 gene may predict resistance to response to cisplatin chemotherapy in patients with lung cancer.
The NPRL2 protein was analyzed in 40 lung cancers and low expression of NPRL2 was correlated with resistance to cisplatin, one of the mainstays of chemotherapy for lung cancer. In lung cancers that were resistant to cisplatin, re- introduction of the normal NPRL2 gene resulted in dramatic re-sensitization to cisplatin.
This effect was confirmed in animal studies using human cisplatin- resistant lung tumors. A 90 percent inhibition of tumor growth was observed with systemic treatment using NPRL2 nanoparticles in combination with cisplatin, compared to control treatments. Thus, NPRL2 may serve as an important biomarker to identify and treat patients with tumors resistant to cisplatin chemotherapy.
These studies were further highlighted by The University of Texas M. D. Anderson Cancer Center in the November issue of their electronic publication Cancer Wise which may be accessed at http://www.cancerwise.org .
Dr. Sunil Chada, Introgen associate vice president for Clinical Research and Development stated, “The ability to use a simple biomarker assay for NPRL2 to identify patients who would not derive benefit from cisplatin represents an important advance and underscores the significance of NPRL2 in lung cancer. Development of NPRL2 gene drugs using systemic nanoparticle delivery may help patients whose tumors are resistant to cisplatin by re-sensitizing tumors to this commonly used therapy.”
NPRL2 has been identified by the International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium, including researchers from M. D. Anderson Cancer Center, The University of Texas Southwestern Medical Center, and the National Cancer Institute. The NPRL2 gene was identified within a “genomic hotspot” of cancer causing mutations at the region of the third human chromosome termed 3p21. This region is frequently deleted or mutated in early stage lung cancer.
Introgen previously announced that it acquired the exclusive worldwide license for a family of at least 10 anti-cancer genes identified by the consortium including NRPL2 and FUS1. Introgen is developing INGN 401 which utilizes the FUS-1 tumor suppressor gene in a nanoparticle formulation and is now in clinical testing for the systemic treatment of metastatic non-small cell lung cancer. Additional genes within this genomic hotspot also appear to be important in control of cancer progression and may function as therapeutic genes as well as prognostic biomarkers.
Mutations in the 3p21 region of chromosome 3 are found in approximately 90 percent of small-lung cancer, more than 50 percent of non-small-lung cancer, as well as in renal, breast, pancreatic, oral and uterine cancers. Mutations in the 3p21 region of the genome are the earliest genetic abnormality currently detected in lung cancer, suggesting that one or more of these genes could act as “gatekeeper,” preventing cells from becoming cancerous.