Melbourne researchers have discovered that some of the most aggressive forms of cancers can be more effectively treated if chemotherapy is combined with a new class of anti-cancer drugs.
The researchers at Melbourne's Walter and Eliza Hall Institute, led by Professors Geoff Lindeman and Jane Visvader along with colleagues Dr Samantha Oakes and Dr François Vaillant, have found that by combining a conventional chemotherapy with another anti-cancer drug, a BH3 mimetic, brings improved results.
According to lead researcher Professor Geoff Lindeman while cancer cells are damaged by chemotherapy, BCL-2 proteins have been found to protect them and thereby preventing them from being completely destroyed. The team combined chemotherapy with ABT-737 drugs and found it to be more effective among mice that had Basal-like breast cancer.
Professor Lindeman wrote in his report that has been published in the Proceedings of the National Academy of Sciences, “In a couple of the models we looked at, chemotherapy alone was not effective in treating these tumors in mice but when combined with the new anti-BCL-2 treatment a durable response was seen in the mice with shrinkage in the tumors.”
Basal-like breast cancer is a more aggressive subtype of breast cancer and accounts for 20 per cent of all cases of breast cancer. He said, “Once the tumor is removed ... followed often by some local radiotherapy ... there are very few treatment options apart from chemotherapy because these sorts of tumors don't respond to hormone therapies or anti-HER2 therapies. In cancer it seems that the BCL-2 proteins can actually protect cells that have been damaged by chemotherapy so that it actually helps prevent the cancer cells from dying from the cancer therapy.”
Professor Lindeman says he thinks the research will provide a strong base for future clinical trials. “This is of course quite different to simply treating patients, so we're a way off knowing what the efficacy would be in humans….But it's certainly enough pre-clinical evidence, I think, to make a strong case for this to be tested over the next few years in clinical trials,” he said. Professor Lindeman says there is also the possibility the procedure will be able to treat other forms of breast cancer. “The tumors that we studied were the Basel-like breast cancers, but really the key target here is BCL-2, and we know that some 70 per cent of breast cancers express BCL-2 or have high levels of this BCL-2 pro-survival protein….So, therefore, it's quite possible that other types of breast cancer could also be amenable to this kind of therapy in combination with chemotherapy,” he said.
Visvader said combined treatment with ABT-737 and docetaxel, a commonly used chemotherapy drug for treating breast cancer, in mice transplanted with human breast cancer cells improved tumour response and survival rates, when compared to docetaxel as a single agent. “The research suggests that these agents make the cancer cells more vulnerable to chemotherapy,” Visvader said. “We are particularly excited that the research shows a good response in Bcl-2-expressing breast cancer, including basal-like breast cancer, which is often the most aggressive and hardest to treat.”
ABT-737 and navitoclax, another Bcl-2 mimetic, are not yet available for patient treatment, but navitoclax is currently in phase II clinical trials to establish its efficacy in treating some types of leukaemia and lymphoma. Navitoclax is being jointly developed by Abbott and Genentech.
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