Breast cancer studies pinpoint potential new drug targets to fight resistance

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Now, two research groups from Italy and the University of California, San Francisco (UCSF) have identified different mechanisms in breast cancer that they say could inspire the development of new drugs to improve response to existing treatments. The Italian team, led by Francesco Nicassio from the Center for Genomic Science at the Italian Institute of Technology in Milan, focused on cancer stem cells, which can self-renew and give rise to new cancer cells. These stem cells are considered an attractive target in cancer research, not just because they promote tumor formation and progression, but also because they’re often resistant to traditional radiation therapy and chemotherapy. Nicassio and colleagues hypothesized that short non-coding RNA molecules called microRNAs might assist cancer stem cells by regulating mRNA to control the types and amounts of proteins the cells make. “We wanted to identify microRNAs required for the maintenance of normal mammary stem cells that are inherited by cancer stem cells and could represent potential therapeutic targets in breast cancer,” Nicassio explained in a statement. The team pinpointed two related microRNAs, miR-146a and miR-146b, that are present in both breast cancer stem cells and normal adult stem cells. The two microRNAs were found to be elevated in aggressive breast cancers bearing a high number of cancer stem cells. According to the study, published in the Journal of Cell Biology, the researchers showed that the two molecules are essential for maintaining cancer cell populations. Patient-derived cancer cells without these two miroRNAs showed a reduced ability to form new tumors when transplanted into mice. Removing miR-146a/b made breast cancer stem cells over 20 times more sensitive to methotrexate, a chemotherapy that works by inhibiting cancer cells from replicating its DNA. The researchers suggested that mir-146a/b regulates processes that are key for cell metabolism and DNA replication.“While the molecular details remain to be determined, our results clearly show that reducing miR-146a/b levels represents an attractive approach to overcome some forms of drug resistance in the clinical setting, unmasking a 'hidden vulnerability' exploitable for the development of anti-cancer stem cell therapies,” Nicassio said.

European Journal of Clinical Oncology Cancer poses a major challenge to development; it undermines socio-economic advances throughout the world. It is estimated that the number of patients with cancer would increase from 12.7 million in the year 2008 to 22.2 million by 2030. It is universally agreed that the condition is reaching epidemic proportions. At this time, the European Journal of Clinical Oncology is conveniently placed in the scholarly communication milieu to help counter the menace of cancer by aiding the development of novel treatment strategies, by providing novel insights into the mechanisms underlying this complex disease.

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John Robert

Managing Editor
European Journal of Clinical Oncology
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