But a recent discovery by a team of Montreal researchers about the genetic mechanisms that play a role in an aggressive form of the disease known as triple-negative breast cancer raises new hopes for some of those affected by it. Dr. Jean-Jacques Lebrun and his team at the McGill University Center for Health Research Institute not only identified which group of genes play a role in tumor progression, but also revealed what could be a promising treatment. Lebrun, who has been researching cancer since he was appointed to McGill about 25 years ago, said the team focused on triple-negative breast cancer, or “TNBC,” to address what he described as a medical vacuum. “There are some breast cancers that can be treated with medication or surgery, but with triple-negative breast cancer, there are no effective, targeted treatments,” he said. “The only solution we usually have is chemotherapy and radiotherapy.” The story goes on under the ad
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Existing drugs and therapies target specific proteins, such as estrogen receptors, progesterone receptors, or human epidermal growth factor (HER2) receptors, which are normally found in breast cancer cells. For example, those with HER2-positive breast cancer will be tested positive for the HER-2 protein. Lebrun said a drug called Herceptin could be used to treat these conditions. “It’s an antibody that targets this receptor,” he explained, while tamoxifen – an anti-estrogen therapy – works well for women with hormone-receptor-positive breast cancer. TNBC does not express any of these three proteins, which means that the cells are negative in all three tests, hence the “triple negative” in the name. And while TNBC is less common – it accounts for only 15 to 20 percent of all breast cancers – Lebrun says it is by far the deadliest, accounting for half of all deaths. “Mortality rates are very high and overall survival rates are very low. “So people with this disease usually have months of life, not years,” he said. The change in these results is what prompted Lebrun’s team to face TNBC.
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The story goes on under the ad Instead of using a hypothesis-based approach, which would mean choosing a protein and trying to target it, Lebrun said they chose a systemic approach. But that meant controlling the entire human genome, or about 20,000 genes. “We want to know which of these are really important in the tumor formation process in these TNBCs,” he said. To do this, the scientists used a gene processing technology known as CRISPR to cut each of the 20,000 genes one at a time in a process known as “silencing” or “removal.” And while it was not like looking for a needle in a haystack, Lebrun said it was a laborious process. “When we started about five years ago, technology was there, but it was just born,” he told CRISPR. “So what sounds a lot easier today was a lot harder at the time, because we had to develop and optimize a lot of the tools ourselves.” Trending Stories
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After the analysis, Lebrun said they were able to limit their search to about 350 genes, eventually identifying two important signaling pathways or gene networks. The story goes on under the ad “One of them was an oncogenic road. “These are genes that normally promote cell proliferation in tumors and this has been overactive in these breast cancer patients,” Lebrun said. The second group of genes, which normally function as tumor suppressors by inhibiting cell proliferation, have been found to be inactive or dormant. This combination, Lebrun believes, could explain why TNBC tumors are so “aggressive and metastatic.” 4: 45Health Matters: New Post Raises Concerns About Breast Cancer Screening Guidelines Health Matters: New Post Raises Concerns About Breast Cancer Screening Guidelines – Nov 25 Understanding the genetic mechanisms involved allowed the team to uncover existing drugs that targeted these networks. One of the drugs they tried, Verteporfin, paradoxically had nothing to do with cancer. “It’s actually a drug used to treat retinal degeneration. “It’s an eye disease,” Lebrun said. The story goes on under the ad “When we saw that this drug was able to target the genes we were interested in, we said, ‘Let’s try it for the other network.’ In total, the team evaluated about 10 different drugs, with Verteporfin being one of the two that stand out. “When we tried each drug separately, they both worked,” Lebrun said. “So we were very happy because it somehow validated our whole strategy, which was to identify the gene, find the corresponding drugs and prove that both drugs work.” However, Lebrun’s team was pleasantly surprised to find that when combined, the drugs had a much greater effect than expected. Individually, each drug had about a 20 percent reduction in tumor growth, so in combination, Lebrun said they expected an inhibition of about 40 percent. “But we have just over 80 percent,” he said. “This is what we call a synergistic effect.” Lebrun and the award-winning RI-MUHC team. Courtesy of Jean-Jacques Lebrun The story goes on under the ad The work of the team did not go unnoticed. He was recently awarded the prestigious 2021 Discovery of the Year Prize by Québec Sciences. “It means a lot.… I’m very happy for the team,” Lebrun said. And while Lebrun is happy with the distinctions, he is not one to rest on his laurels. “I think it is a significant step forward in the field,” he said. “But you know, when I see it reflected in a clinical trial, then I’m happier.” Efforts have been made since the summer to begin Phase 1 clinical trials, but Lebrun says there are many obstacles that need to be overcome. The first is that trials take time to organize. Lebrun said there is a lot of administrative work and you also need ethical approval to move forward. Then there is the cost of the test itself. “It’s complicated because you need sponsors,” Lebrun said. “Even the Phase 1 clinical trial – you need millions of dollars to get started.” The story goes on under the ad And that does not include the cost of the drugs themselves, some of which, like Verteporfin, can be extremely expensive to produce, according to Lebrun. “When you are going to do this to people, you need huge amounts of these drugs and that is something we sometimes do not think about,” he said, reiterating the need for collaboration. And while discussions are under way, Lebrun said he could not give a timeline for when the trial would begin and when patients could start enrolling. “But this is our next step.” © 2022 Global News, part of Corus Entertainment Inc.
