The new study was published in the current edition of Clinical Cancer Research, a journal of the American Association for cancer research. Seliciclib is currently in Phase 2 clinical trials for non-small cell lung cancer and nasopharyngeal cancer.
Approximately 3 out of 4 women suffering from breast cancer after menopause have cancers that express the hormonal receptors for estrogen and progesterone and are offered treatment with aromatase inhibitor drugs including letrozole. Letrozole is believed to interact with a natural CDK inhibitor p27 which in turns regulates the activity of the CDK2/cyclin E complex. Over time, breast cancer cells develop resistance to letrozole and the therapy becomes ineffective.
Researchers from The University of Texas MD Anderson Cancer Center led by Khandan Keyomarsi, professor in the Department of Experimental Radiation Oncology, found that a key cause of resistance to letrozole is overexpression of the low molecular weight form of cyclin E, which also predicted for lower overall survival and higher chance of cancer recurrence after aromatase inhibitor treatment.
However, after they treated letrozole-resistant breast cancer cells with seliciclib, a CDK2/cyclin E inhibitor, the resistant cancer cells were killed. The researchers concluded that their data support clinical investigation of CDK inhibitors such as seliciclib as targeted therapy in a specific patient population of postmenopausal women with hormone receptor positive, low molecular weight cyclin E expressing breast cancer.
David Glover, chief scientist of Cyclacel, said: “Resistance to aromatase inhibitors, such as letrozole, is a major challenge for the long-term management of hormone receptor positive breast cancer. The data published in Clinical Cancer Research are encouraging as they show that seliciclib can kill resistant breast cancer cells by targeting a form of cyclin E that is a major cause of the resistance. This is further evidence that seliciclib’s unique mechanism of action can be effective against certain cancer cells, such as breast and lung cancer, that fail to respond to standard cancer treatments.”