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An international team of scientists discovered that the addition of a component already clinically approved of medicinal cannabis to standard chemotherapy can triple the survival time in mice with pancreatic cancer . They suggest that if the results can be replicated in human trials, dual therapy could quickly become adopted for routine use, and ultimately prolong patients' lives. At Queen Mary University in London, led by Marco Falasca, Ph.D., the research team treated mice with pancreatic tumors using a combination of standard gemcitabine (GEM) chemotherapy and the cannabidiol (CBD), a non-psychoactive cannabinoid that inhibits the G protein-coupled receptor, GPR55. They found that, compared with untreated animals, or those treated only with gemcitabine, the combination of cannabidiol and chemotherapy led to a "remarkable increase in survival."
"Cannabidiol is already approved for use in clinics, which means we can quickly "If we could reproduce these effects in humans, cannabidiol could be used almost immediately in cancer clinics, compared to the expectation of approval." a new medicine by the authorities. "
reporting their findings in Oncogene researchers at Queen Mary College, working with colleagues at Curtin's Health Innovation Research Institute at Curtin University in Australia and with scientists in Italy and the Kingdom One, claim that their results represent "a huge step forward in identifying a new treatment regimen that could greatly benefit PDAC patients." Their published article is titled, "GPR55 signaling promotes proliferation of pancreatic cancer cells and tumor growth in mice, and its inhibition increases the effects of gemcitabine."
Pancreatic ductal adenocarcinoma remains the only way to treat pancreatic cancer. one of the most aggressive forms of cancer and the life expectancy of patients has improved little in 40 years, write the authors. The one-year survival rate is only 19% and the five-year survival remains at about 5%, and the need for new therapeutic strategies is "urgent". Until recently, GEM was the only treatment approved by the FDA, but in most cases, chemotherapy only prolongs the survival of a few weeks. According to the researchers, newer treatments may increase survival, but only 2 to 4 months compared to treatment with gemcitabine.
More and more evidence suggests that GPR55 plays a key role in many types of cancer. targeting the receptor could improve cancer survival, and whether the strategy could represent a feasible therapeutic approach. "Indeed, no study has so far investigated whether the inhibition of GPR55 could enhance the survival of transgenic models that closely mirror human disease," the authors added.
To investigate this potential more closely, they used genetic and pharmacological approaches to block GPR55 in the PDAC KPC mouse model. Initial studies have shown that GPR55 gene suppression inhibits cancer proliferation and significantly improves survival, confirming that "GPR55 is crucial for PDAC development and / or in vivo progression," noted the team. noting that its first results
from other studies in PDAC cell lines have shown that GPR55 downregulation reduces cell proliferation and growth by interrupting the cell cycle, while additional experiments in genetically modified mice have indicated that the expression of pancreatic cancer proliferation. GPR55 protein is naturally downregulated by the TP53 tumor suppressor protein, which modulates microRNA (miRNA) miR34b-3p levels.
The authors suggest that these results suggested a mechanism by which mutations in TP53 could promote cell growth. regulating the levels of miR34b-3p ", which in turn results in increased GPR55 ion and increased proliferative signals." As miR34b-3p itself has previously been reported to be downregulated in PDAC and D & # 39; having a key role in PDAC progression, our data identify a new p53 / miR34b-3p / GPR55 axis in this process. "
The researchers then tested the inhibition of GPR55 protein both in vitro and in the PDAC model of the mouse.The initial tests in PDAC cell lines showed that the cannabinoid inhibitor GPR55 CBD blocked PDAC cell and cell cycle progression They then tested the effects of therapy using either the CBD alone, CBD plus gemcitabine, in the PDAC mouse model, showed that although the mice survived for similar times when they received either CBD or gemcitabine alone, on the other hand, and in a "striking" way, they wrote "a remarkable and statistically significant increase in val. was observed when the CBD was used in combination with GEM, with a survival almost three times that of the mice … "
When the researchers badyzed tumor samples in the mice, they discovered that the combination of drugs inhibited the proliferation of cancer cells. much more than CBD or gemcitabine alone. Detailed immunohistochemical badyzes suggested that CBD had an impact on the pathways involved in acquired resistance to gemcitabine. This finding is particularly important because the development of drug resistance is "one of the main reasons for such an" abysmal prognosis, "notes the team." Our demonstration that a combination of CBD and GEM can oppose the mechanisms badociated with drug resistance and increase the survival of KPC mice is very important considering that both drugs are already approved for medical use and therefore this combination can be quickly tested in the clinical tests. "
They point out that the study also provides the first validation of GPR55 as a potential target for cancer treatment that could have an impact on the prognosis and survival of the disease." To the best of our knowledge, our Study is the first demonstration that the inhibition of GPR55 not only reduces cancer progression in a well-established transgenic model, but it also represents a therapeutically valid strategy. "
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