Researchers Say Single Molecule May Lower Mesothelin Levels

A group of cancer researchers have discovered that the single microRNA molecule, MiR-21-5p, lowers levels of mesothelin (MSLN). To understand what this discovery means, it is important to understand the role of mesothelin and microRNAs. Mesothelin is a protein found on the surface of certain types of normal cells and cancer cells. Mesothelin may help these cells stick together and send signals. A higher-than-normal amount of mesothelin is found on some cancer cells, including mesothelioma, ovarian cancer, and pancreatic cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate messenger RNA (mRNA) expression mainly by silencing target transcripts via binding to miRNA recognition elements (MREs) in the 3’untranslated region (3’UTR). RNA (ribonucleic acid) is a nucleic acid present in all living cells.

During the study titled “Identification of MiR-21-5p as a Functional Regulator of Mesothelin Expression Using MicroRNA Capture Affinity Coupled with Next Generation Sequencing,” the team of eight researchers conducted in vitro experiments that showed treatment with microRNA molecule miR-21-5p mimic reduced production of malignant pleural mesothelioma (MPM) cell lines. The researchers concluded that, “MiR-21-5p is suggested as novel regulator of MSLN with a possible functional role in cellular growth.”

The hope is that, with further study and development, MiR-21-5p could potentially be used in combination with other MPM treatment protocols to lower levels of MSLN, thus slowing the progression of the disease.

Current Malignant Pleural Mesothelioma Treatment Protocols

Current standard treatment protocols for malignant pleural mesothelioma include surgical intervention, chemotherapy, radiation therapy, and trimodality therapy. Trimodality therapy is a triple combination of chemotherapy, radiation therapy, and surgery. The following is a breakdown of when each therapy may be used and in what, if any, combination.

Stage I Resectable:

Patients with operable disease may receive extrapleural pneumonectomy (EPP); positive margins, add radiation therapy.

Extrapleural Pneumonectomy involves dissection of the parietal pleura and division of the pulmonary vessels, as well as en bloc resection of the lung, pleura, pericardium, and diaphragm, followed by reconstruction. –MedScape

Radiation Therapy uses beams of intense energy to kill cancer cells. Radiation therapy most often gets its power from X-rays, but the power can also come from protons or other types of energy. –Mayo Clinic

Stage I Unresectable:

• Observation for disease progression or
• Chemotherapy
• Radiation for positive margins

Chemotherapy works by stopping the growth of cancer cells, which divide quickly. It is used to cure cancer, lessen the chance it will return, or stop or slow its growth. Chemotherapy is also used to shrink tumors that are causing pain and other problems. –National Cancer Institute (NCI)

Chemotherapy can be administered orally in pill form, intravenously (into a vein), or injected into a muscle (intramuscular), a body cavity, or into the spinal fluid (intrathecal). Common chemotherapy drugs for the treatment of MPM include Pemetrexed (Alimta), Cisplatin (Platinol and Platinol-AQ), and Gemcitabine (Gemzar).

Stages II-III Resectable:

• Induction chemotherapy (Cisplatin and Pemetrexed) or
• Surgery (pleurectomy/decortication or extrapleural pneumonectomy)
• Radiation

Pleurectomy/Decortication is a more limited procedure than extrapleural pneumonectomy, and requires less cardiorespiratory reserve. It involves dissection of the parietal pleura, incision of the parietal pleura, and decortication of the visceral pleura, followed by reconstruction. This procedure has a morbidity of 25% and a mortality of 2%. –MedScape

Stages II-III Unresectable:

• Chemotherapy is recommended
• Radiation for palliation and positive margins

Stage IV:

• Chemotherapy
• Radiation post chemotherapy for palliation
• Surgery is not recommended for patients with stage IV disease

Doctors look to common cancer treatments such as these as a first line of defense against mesothelioma. However, hundreds of drugs, therapies, and treatments are currently being studied for the treatment of mesothelioma. Some have been successful in these studies, while others show promise.

Studies are actively recruiting participants to receive groundbreaking treatments that could be effective in helping treat specific types of mesothelioma.

 

Sources

"Chemotherapy for Malignant Mesothelioma." American Cancer Society. American Cancer Society, Inc., 2017. Web. 27 Mar. 2017.

"Chemotherapy." National Cancer Institute (NCI). U.S. Department of Health and Human Services, National Institutes of Health (NIH), 29 Apr. 2015. Web. 27 Mar. 2017.

"How Is Chemotherapy Delivered?" UNM Comprehensive Cancer Center. University of New Mexico (UNM) Health Sciences Center, 2016. Web. 27 Mar. 2017.

"NCI Dictionary of Cancer Terms." National Cancer Institute (NCI). U.S. Department of Health and Human Services, National Institutes of Health (NIH), n.d. Web. 27 Mar. 2017.

Mayo Clinic Staff. "Tests and Procedures: Radiation Therapy." Mayo Clinic. Mayo Foundation for Medical Education and Research (MFMER), 1998-2017. Web. 27 Mar. 2017.

Santi, Chiara De, Sebastian Vencken, Jonathon Blake, Bettina Haase, Vladimir Benes, Landi Stefano, and Catherine Greene. "Identification of MiR-21 as a Regulator of Mesothelin Expression Using MicroRNA Capture Affinity Coupled with next Generation Sequencing." European Respiratory Journal 48.Suppl 60 (2016): n. pag. Web.

Tan, Winston W., Jasmeet Anand, Christopher D. Braden, and Jules E. Harris. "Malignant Pleural Mesothelioma Treatment Protocols." MedScape. WebMD, LLC, 28 Oct. 2016. Web. 27 Mar. 2017.

The Editors of Encyclopædia Britannica. "Messenger RNA (mRNA)." Encyclopædia Britannica. Encyclopædia Britannica, Inc., 01 Apr. 2016. Web. 27 Mar. 2017.