| CCIA scientists find a breakthrough for lung cancer treatment.
In a study published in the prominent international journal, Cancer Research, scientists have found that targeting a protein known for maintaining the structural integrity of cells, could be key to increasing drug sensitivity in one of the most lethal types of cancers, non-small cell lung cancer.
The Pharmacoproteomics Program at Children’s Cancer Institute Australia for Medical Research (CCIA) and the University of News South Wales found that in clinically relevant models of lung cancer, suppressing ?III-tubulin, part of the cytoskeleton of the cell, increased the sensitivity of the cancer to standard chemotherapy drugs.
Associate Professor Maria Kavallaris, Head of the research program at the Lowy Cancer Research Centre, said these findings could advance new ways of approaching treatment of non-small cell lung cancer, which accounts for 80% of all lung cancers.
“Traditionally, non-small cell lung cancer is often treated with drugs that target tubulin, important proteins involved in cell division, along with drugs that damage the cellular DNA and destroy tumour cells,” A/Prof Kavallaris said.
“The prognosis for patients with advanced non-small cell lung cancer continues to be dismal as the tumours frequently become resistant to this drug therapy.
“By understanding more about what ?III-tubulin does and the role it plays in countering drug resistance we can improve the efficacy of these drugs,” A/Prof Kavallaris said.
“Of particular significance, we also found that suppressing ?III-tubulin decreased the incidence and progression of lung cancer independently of chemotherapy drugs.
“This is an important piece in the puzzle and has direct clinical relevance for the more than 9000 Australians diagnosed with non-small cell lung cancer every year.
The Australian biotechnology company, Benitec, has recognised the potential of this research and has entered into a research partnership with A/Prof Kavallaris and NewSouth Innovations Pty Ltd (NSi)* to develop therapeutics focused on specifically blocking ?III-tubulin activity using its proprietary RNA interference technology, to improve patient outcomes for this particularly aggressive cancer.
*NSi , Commercialisation arm of the University of New South Wales
Published Paper Abstract: Advanced non–small cell lung cancer (NSCLC) cell has a dismal prognosis. ?III-Tubulin, a protein highly expressed in neuronal cells, is strongly associated with drug-refractory and aggressive NSCLC. To date, the role of this protein in in vivo drug resistance and tumorigenesis has not been determined. NSCLC cells stably expressing ?III-tubulin short hairpin RNA displayed reduced growth and increased chemotherapy sensitivity when compared with control clones. In concordance with these results, stable suppression of ?III-tubulin reduced the incidence and significantly delayed the growth of tumors in mice relative to controls. Our findings indicate that ?III-tubulin mediates not only drug sensitivity but also the incidence and progression of lung cancer. ?III-Tubulin is a cellular survival factor that, when suppressed, sensitizes cells to chemotherapy via enhanced apoptosis induction and decreased tumorigenesis. Findings establish that upregulation of a neuronal tubulin isotype is a key contributor to tumor progression and drug sensitivity in lung adenocarcinoma. Cancer Res; 70(12); OF1–9. ©2010 AACR.
Full text here - http://cancerres.aacrjournals.org/cgi/reprint/70/12/4995
Technology: Benitec, an Australian ASX listed biotechnology company, owns the worldwide rights for the technology used in this study of DNA-directed RNA interference directed to ?III-tubulin in non-small cell lung cancer.
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