A new study has identified micro RNA (miRNA) MIR1249 as a key player in genetically altering cancer cells to become resistant to chemotherapy. This discovery opens new possibilities in the field of drug research and development, in that this miRNA could be a more favorable biomarker to target than more conventional treatments that block proteins.
Unlike other forms of RNA, miRNA does not help translate the DNA code into proteins. Instead, it seems to be crucial for controlling the signaling networks within cells. Scientists at The Institute of Cancer Research in London have found that MIR1249 plays a key role in allowing bile duct cancers to resist chemotherapy by allowing them to change their protein expression as needed.
The results from this study, published in the journal Hepatology, show that MIR1249 is capable of hijacking the WNT signaling network, an important signal in normal cells that can be co-opted by cancer cells. The WNT network is involved in the upkeep of stem cells, allowing them to morph into their intended cell type, but under cancerous conditions WNT seems to give cancer cells the features of stem cells, allowing them to become more resistant to treatment and able to survive the onslaught of chemotherapy.
The researchers hope that by discovering the role MIR1249 plays, it can become a potential target for new drugs in bile duct cancer and allow current chemotherapy drugs to become much more effective with co-treatment. Bile cancer is a particularly difficult type of cancer to treat with conventional methods, but researchers also believe that the mechanism driving resistance may be shared with other cancer types – raising the possibility of a common treatment pathway in the field of cancer research.
Study leader Dr Chiara Braconi, who carried out the research, said: “Our study shows the crucial role played by a piece of micro RNA in rewiring the network of signals within cancer cells and helping them to resist the effects of chemotherapy.”
She continued, “It identifies MIR1249 as a potential drug target in bile duct cancers and possibly other tumor types, and opens up what could be an exciting new avenue of treatment. It’s remarkable how such a tiny piece of RNA can play such a significant role in rewiring cancer cells so that they can resist chemotherapy. There is growing interest in the idea of developing drugs against RNA rather than against proteins, as studies like ours show the important role of micro RNA in cell signaling.”
In the study, which involved mice and human tissue samples, data revealed that by blocking MIR1249 activity, cancer cells became more sensitive to chemotherapy and thus responded better to treatment.
The researchers also found that 41% of bile duct cancers had increased levels of MIR1249, suggesting it could be playing an important role within these tumors. In support of this theory, MIR1249 was also statistically associated with poorer survival outcome, suggesting the more MIR1249 that is present, the harder it is to kill the cancer with chemotherapy.
Study co-author Professor Paul Workman, added: “Bile duct cancer is becoming increasingly common around the world and survival rates are very poor, so there is an urgent need to develop better therapies for people with advanced disease whose treatment stops working. This new study shows the potential of targeting molecules called micro RNAs as a new form of treatment for drug-resistant cancers.
“At the IRC, we believe overcoming cancer evolution and drug resistance is the biggest challenge we face today in the field of cancer research. Through our new Centre for Cancer Drug Discovery, we are aiming to find new ‘anti-evolution’ treatments that can offer long-term control or cure even for advanced cancers.”
News of this development has reached patients as well as scientists, and patients are elated at a new prospect for future drugs and treatment options. Currently, a diagnosis of bile cancer has bleak implications.
Sal Cheema, 42, from Uxbridge, UK is a patient who was diagnosed with stage 4 bile duct cancer in 2018. She stated: “I had chemotherapy for eight months which kept my cancer at bay. But within six weeks, I was devastated to learn that the cancer had spread to my lymph nodes.
“Bile duct cancer is rare, yet the incidence is increasing and it’s not known why. This cancer is also affecting younger people more and more, so it’s imperative that this specific research continues – not only for bile duct but other cancers too.
She continued, “There are very few treatment options for bile duct cancer patients, so I’m elated to hear of this research and discovery as it could open up a whole new way of targeting the cancer. More targeted treatments with fewer side effects are vital – these findings are very promising for people like me.”