The USA's Cyclacel Pharmaceuticals has reported data from a study showing synergistic activity between its investigational therapy seliciclib and multiple epidermal growth factor receptor inhibitors, including Roche's Tarceva (erlotinib) in models of non-small cell lung cancer, and the HER2-targeting agent Herceptin (trastuzumab) in models of breast cancer.
These preclinical results were published in the July issue of the journal, Clinical Cancer Research. Cyclacel's orally-available cyclin-dependent kinase inhibitor, is currently being tested as a single agent in the Phase IIb APPRAISE trial in patients with non-small cell lung cancer and in a Phase II study in nasopharyngeal cancer.
In the published study, in vitro combination of seliciclib and Herceptin resulted in greater loss of cyclin D1 and increased down-regulation of HER2 than either compound produced independently. Similarly, the combination of seliciclib and EGFR inhibitors resulted in an increased down-regulation of EGFR and greater reduction in cyclin D1 than either compound produced alone. In both studies, the effects on ErbB receptors and cyclin D1 production were expressed as a synergistic inhibition of tumor cell growth, producing significantly greater inhibition than either drug when given alone, the firm noted.
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