Nat commun: researchers have found a clue to the drug resistance of medulloblastoma

February 15, 2020 / bioun / -- Timothy Gershon, associate professor of Neurology at the University of North Carolina's Chapel Hill School of Medicine (UNC), and Kirk Wilhelmsen, Professor of Neurology and genetics They have identified specific cell subtypes that lead to the failure of targeted treatment of a subtype of neuroblastoma, reports communications They found that although most cells responded to the treatment, different cell groups in the tumor continued to grow and developed resistance to the treatment "Based on our findings, we conclude that the diversity of tumor cells enables them to rapidly develop resistance to precise targeted therapies," Gershon said Our data show that because of the diversity of tumor cells, molecular targeted therapy should be combined to be effective "Image source: nature communications Gershon and colleagues focus on a tumor subtype that accounts for a third of medulloblastoma cases This subtype is characterized by activation of the signal from the hedgehog cell, which helps trigger other signals in developing brain cells, leading to over growth of neurons in the cerebellum This area of the brain controls balance, language, and other activities They want to know about the drug resistance of vismodegib, which has shown potential in early clinical trials to treat neurotubuloma with active signal of hedgehog factor However, the researchers said the study found that many patients developed drug resistance "Although patients initially respond, the frequency of drug resistance during treatment is very high," Gershon said "Resistance to treatment of medulloblastoma subtypes in laboratory studies of mice with this neuroblastoma subtype, the researchers analyzed the response of tumor cells to vismodegib treatment They found that although the drug initially controlled tumor growth, different cell groups reacted differently to the drug, allowing the tumor to regenerate rapidly Most cells respond to drugs and mature like normal brain cells, but some cells are still undifferentiated and continue to divide These cells also have active gene signals of sonic hedgehog factor - indicating that the drug does not effectively shut down the signaling pathway it targets They found some markers of resistant cells The most common group of resistant cells expressed MyoD1 gene These cells existed even before vismodegib treatment "Anti drug cells are present at the beginning of the treatment," Gershon said "After three days, these cells are enough to replace the inhibited cells "They also found a group of stem cells expressing Sox2 gene, which are resistant This population was previously thought to be resistant, but researchers now know that it is not the only culprit Gershon said the findings suggest that further research should evaluate targeted treatment combinations for this type of medulloblastoma in order to effectively inhibit the growth of cancer cells, as there are multiple cells in the tumor from the beginning "The only effective way to target therapy is to combine therapies with overlapping targets," he said "New findings in cancer cell biology researchers also report a finding that they say is important to understand how cancer cells develop They found that cancer-related mutations can return cells to an earlier, undifferentiated state, becoming more like stem cells Some researchers assume that cancer develops from stem cells, but Gershon said their findings show that the process from stem cells to mature cells is two-way, and cancer cells can mature or return to their pre mature state Gershon said: "genetic changes within a tumor can cause the tumor to move in a stem cell like direction This discovery is of great significance for us to understand the development of cancer It shows that the maturation of cancer cells is bidirectional, and cells can move forward or backward "Reference: Jennifer ocasio et al Scrna SEQ in dulloblastoma shows cellular genetics and lineage expansion support resistance to Shh inhibitor therapy, nature communications (2019) Doi: 10.1038/s41467-019-13657-6