Category: Featured News
Chemicals Identified As Potential Targets for Lung Cancer May One Day Be Focus for Personalized Mesothelioma Treatments
After five years spent testing and retesting over 200,000 different compounds as candidates to be used in the treatment of lung cancer, researchers narrowed the list down to 170 chemicals. Now, the team plans to delve deeper into the mechanisms of the compounds and to assess the effectiveness against other types of cancers. Potentially, mesothelioma and other aggressive cancer patients will benefit from the new discovery.
The team of researchers from University of Texas Southwestern Medical Center, using the Center’s “unique lung cancer cell library,” set out to identify therapeutic triads, according to an April 19 press release. The search required testing against a trifecta of criteria including finding chemicals that kill cancer cells, biomarkers that predict who would respond, and the therapeutic targets on which those active chemicals work.
The 170 chemicals were tested against 100 lung cancer lines to confirm they all met the three sets of criteria. The resulting chemicals are called the Precision Oncology Probe Set, or POPS. This testing approach is considered unusual for cancer research with the team looking at drugs first, then cancers.
“Almost all cancer research is gene-first, or target-first. We began with the potential drugs,” said Dr. Michael Roth, Professor of Biochemistry and a member of the Simmons Cancer Center.
The researchers report that these findings are “a significant step forward toward personalizing cancer care.” They report that for most of the compounds they identified a biomarker that can lead to the development of precision medicine. This means patients with those biomarkers can receive individualized care.
Personalized care targeted to the unique characteristics, such as the biomarkers, of a mesothelioma patient increases the chance of success, and can extend their survival and improve their quality of life. For most mesothelioma patients, life expectancy is less than a year after diagnosis and they often struggle with daily living tasks. There is no cure, and there are limited treatments for the asbestos-caused cancer.
UT Southwestern researchers are known for their innovative approach to cancer research with their findings bringing hope to the mesothelioma community. MesotheliomaHelp has reported on UT’s research into chili peppers in combating cancer and into a new target in fighting the KRAS gene in cancer. They have also conducted mesothelioma clinical trials.
UT Southwestern Medical Center is one of the few institutions in the country with a treatment and research program dedicated to mesothelioma, according to its website. To find out more about UT Southwestern’s research and treatment for mesothelioma, visit the Mesothelioma program’s website.
Read the full study in the March 28 issue of the journal Cell.
https://www.cell.com/cell/fulltext/S0092-8674(18)30308-8
Sources
- University of Texas Southwestern Medical Center
http://www.utsouthwestern.edu/newsroom/articles/year-2018/170-lung-cancer-drugs.html - Mesothelioma program’s website
https://utswmed.org/conditions-treatments/mesothelioma/ - UT Southwestern Medical Center
https://utswmed.org/conditions-treatments/mesothelioma/
Drug Targeting Specific Protein Could Lead to Personalized Mesothelioma Treatment
Anti-cancer drugs known as kinase inhibitors have often been used in the treatment of pleural mesothelioma and many other cancers. The drugs attack the protein kinases in an effort to prevent cell division and to kill the cancerous cells. Now, researchers report they have found that an investigative drug can effectively shrink tumors in patients with lung cancer and other difficult to treat cancers with a specific kinase. Pleural mesothelioma patients could benefit as well.
According to researchers from The University of Texas MD Anderson Cancer Center, in the first-in-human study of the investigational, oral drug BLU-667, “the drug appears to be promising” in cancers caused by an alteration in the receptor tyrosine kinase known as RET, or rearranged during transfection. The drug is “a highly potent and selective RET inhibitor” shown to have limited toxicity in the patients.
“Tumor reductions and durable responses were observed in most patients, especially those patients whose cancer progressed with chemotherapy and multi-kinase inhibitors,” said Vivek Subbiah, M.D., Assistant professor of Investigational Cancer Therapeutics at MD Anderson Cancer Center, in an April 15 press release.
In the study of 43 patients with advanced tumors not eligible for surgery, 26 patients with thyroid cancer, 15 with non-small cell lung cancer, and two with other RET-driven cancers, the overall response rate was 37 percent for RET-driven cancers, with responses of 45 percent for non-small cell lung cancer and 32 percent for thyroid.
“Overall, the data show the precision targeted therapy with next-generation kinase inhibitors can have a powerful impact for patients with RET-driven cancers,” said Dr. Subbiah.
Kinases function as drivers for numerous types of cancer, including mesothelioma. Kinases are involved in the gradual transformation of normal tissue in the lining of the lung into malignant pleural mesothelioma after exposure to asbestos. Various kinase inhibitors have been used to treat mesothelioma and other cancers, but according to Dr. Subbiah, these “earlier generations of multiple kinase inhibitors” have limited success and come with significant side effects.”
Although researchers have made progress in recent years, identifying an effective treatment modality for the fatal mesothelioma remains elusive. Taking a personalized approach to the treatment of mesothelioma by targeting a patient’s unique genetic characteristics, such as the RET biomarker, offers the most effective treatment options.
“By offering a highly selective medicine tailored for this oncogenic driver, we hope this new therapy will enable patients to benefit from the recent advances in genomic profiling that have revolutionized treatment options for patients with kinase-driven diseases.”
Find the results of the study in the April 15 issue of Cancer Discovery.
Mesothelioma Community Ponders Significance of Newly Discovered Organ
For years, researchers have struggled to find the reason mesothelioma and other cancers aggressively grow and spread throughout the body. Primarily, the focus has been on the spread of cancer cells through the bloodstream. Now, researchers report they have discovered a new organ that could be responsible for unbridled cancer growth.
In a recent discovery, researchers from New York University’s School of Medicine report they found a new organ that sits one layer below the skin. The mesh-like interstitium, as it has been named, is a layer of interstitial tissue filled with and surrounded by interstitial fluid. Although they have known about the tissue and fluid, the way the tissue had been examined in the past, with the fluid removed, it was seen as just another piece of tissue.
According to a March 27 article in the CNN, when the researchers kept the tissue alive and examined it more closely, they found that it has a unitary structure with compartments filled with fluids. The researchers surmised some of the fluid is lymph fluid, of the lymphatic system that supports immunity, and flows through the body through these interconnected compartments. The flow of fluids can also spread diseases, including cancer.
Because the interstitium has a single structure and a single function, Neil Theise, a professor at NYU’s School of Medicine and author on the paper, says it meets the criterium to be considered an organ. The interstitium is throughout the body, like the skin, but he says, it is even larger than the skin.
Thiese believes the interstitium could change the way doctors think about cancer and other diseases. “It’s been known that when cancer invades this layer, either in the skin or in the viscera, that’s when it first becomes able to spread outside the organ of where it arose,” said Theise.
“This discovery will open up new research pathways for inflammation and cancer progression,” added Dr. Petros Constantinos Benias, co-lead author of the study, a member of the Feinstein Institute and an assistant professor at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health.
Mesothelioma is the signature cancer of asbestos caused by inflammation from inhaling the microscopic fibers. The cancer can spread rapidly, and treatments are focused on trying to halt metastasis. This new understanding of how the cancer may travel through the interstitium could lead to a new approach for halting cancer growth.
Much more research still needs to be conducted, but the team suggests that whereas currently blood and tissue samples are used as a diagnostic tool, interstitial fluids may be effective.
“We are optimistic that with what we learned, we’ll soon be able to study and target the interstitial space for diagnosis of disease and perhaps for novel personalized treatments,” said Dr. Benias.
Find the study in the March 27 issue of Scientific Reports.
World Cancer Day Is A Reminder to Support the Mesothelioma Community
February 4 was World Cancer Day, a day to come together to pray for those afflicted with this disease, the families impacted, the warriors still fighting, and a cure. This is time for the entire cancer community to be recognized and bring light to the fact that there is much work to be done to find a cure for all cancers, in order to bring these horrific nightmares to a conclusion.
Clinical trials, experimental treatments, and therapies are all in the news. The awareness this creates is paramount; it could help save someone’s life that hears about them, as well as change millions of lives by their successes.
I am honored to be an active advocate in this community, more specifically the mesothelioma community. I am an unhappy member, but a proud one, working to raise funds and to help others in memory of my Dad. Let’s face it, this is a club that no one wants to be in. There’s no secret handshake, no membership fee, and no perks. This club is full of heartbroken associates; comrades who have endured highs and lows, suffering and joy, throughout their cancer story. The survivors are beautiful examples, the warriors valiant knights, and the lost mourned kinsmen.
No matter what your role is in this narrative, whether you are a patient or a loved one, a medical professional or an acquaintance, we all have a part to play. We need the support of everyone during their battle with cancer in order to end this era in our history, and I believe that it can happen. Advocacy is key, informing the general public about what is going on in the cancer field. Funds are necessary to perform research and help those who cannot afford treatment on their own. Prayers are essential. Time is of the essence. Faith is what will get us through.
So take a little time to think about where you fit. The story can be changed for the better by your support, your willingness to give, and your capacity to love. Let’s work together, and change the way we look at cancer… let’s see it in the rear-view mirror.
Using Epigenetics To Understand Metastasis May Lead to Novel Mesothelioma Treatment
Researchers know that the best way to increase survival in cancer patients is to keep the disease from spreading to other areas. For aggressive cancers like pleural mesothelioma, cancer cells can outfox even the strongest treatments and metastasize, leaving patients with poor survival. Now, researchers report that through epigenetics they discovered a novel way to inhibit the spread of cancer that could lead to a new treatment that ends cancer growth.
In a break from traditional research looking into gene mutations, a team of researchers from Case Western Reserve University School of Medicine of Cleveland, Ohio, used epigenetics, the study of how genes are turned on and off, as a way to distinguish the differences in primary tumors and metastatic tumors. The team knew that “enhancer activity,” or the genes’ ability to turn switches on or off, “lend cells their unique characteristics” and contribute to normal development.
However, faulty activity within the cells can lead to tumor development and the spread of cancer. Upon further inspection of the metastasized tumors, the researchers discovered the on-off switches were “in different positions than in the cells of the source tumor.”
“Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumors to form in the first place,” said the study’s lead author, James J. Morrow, PhD, a medical student in the Medical Scientist Training Program at Case Western Reserve University School of Medicine. “So based on the knowledge that enhancers drive both normal cell development and tumor-formation, we hypothesized that they may play a similar role in the transition of cancer cells from one developmentally distinct tissue to another during metastatic progression.”
Metastasis, according to researchers, is the cause of nearly 90 percent of cancer deaths. Researchers agree that understanding how to stop metastasis is critical for increasing survival in mesothelioma, an asbestos-caused cancer, and other cancers.
Using mouse models of bone cancer (osteosarcoma) cells, the team wanted to find a way to halt the spread of the cancer to the lungs. Through epigenomic profiling, the team found “bunched clusters of enhancers,” metastatic variant enhancer loci (Met-VELs), near the cancer cells that had metastasized to the lungs. Turning to BET inhibitors, a promising class of anti-cancer drugs now in clinical trials, to interrupt the Met-VELs, the researchers were able to inhibit the cancer growth in the lungs.
Based on the success, the researchesr concluded Met-VELs “may be suitable targets” for treatments targeting metastasis.
Using epigenetics as a new approach for finding an effective treatment could bring the breakthrough needed for halting cancer growth and for increasing survival in the nearly 3,000 Americans diagnosed with mesothelioma each year.
The study was published Jan. 15 online in Nature Medicine.
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