Category: Featured News
Mesothelioma Community Excited About First-Ever Gene Therapy Approval From FDA
In July, MesotheliomaHelp reported on the pending approval of two different types of gene therapy for treating cancer and inherited diseases. Last week, the U.S. Food and Drug Administration announced approval of one of the therapies in a landmark approval of the first-ever gene therapy for a type of leukemia. The mesothelioma community is hopeful that this approval will lead to a new treatment for the incurable cancer.
In an August 30 press release, the FDA announced its “historic action” with the approval of Kymriah (tisagenlecleucel), from Novartis Pharmaceuticals Corp., for the treatment of a form of acute lymphoblastic leukemia (ALL). The press release conveyed an air of excitement in announcing that the first gene therapy approval in the United States is “ushering in a new approach to the treatment of cancer and other serious and life-threatening diseases.”
“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” said FDA Commissioner Scott Gottlieb, M.D. “New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses.”
The FDA explains how the new therapy will work:
“Each dose of Kymriah is a customized treatment created using an individual patient’s own T-cells, a type of white blood cell known as a lymphocyte. The patient’s T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein (a chimeric antigen receptor or CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells.”
Known as CAR-T, the new therapy is a process that genetically alters a patient’s own cells to fight cancer. Mesothelioma medical professionals hold out hope that ultimately this gene therapy could ultimately bring an effective treatment to mesothelioma patients.
Expert Insight
Francis S. Collins, M.D., Ph.D., Dir. NIH
“I’m eager to see where our immunotherapy researchers take us next!”
In a 2013 article for MesotheliomaHelp, Ricki Lewis, a science writer with a PhD in genetics, wrote about CAR-T treatment saying, “An ingenious technique that has vanquished leukemia in a handful of patients is also being applied to mesothelioma.” She was referring to a mesothelioma clinical trial from the University of Pennsylvania that uses the “doctored T cells,” known as chimeric immune receptor (CIR) instead of CAR, against mesothelin, a protein that is found to be in excess in mesothelioma and other cancers. The idea is that T cells led to the mesothelioma cells will attract an immune response, said Lewis.
Find out more about the mesothelioma clinical trial from University of Pennsylvania here.
Although the Director of the National Institutes of Health, Francis S. Collins, M.D., Ph.D., heralds immunotherapy as “one of the most exciting areas of progress” in cancer treatment, he notes caution should be taken in the widespread use of the drug, according to an Aug. 30 NIH Director’s Blog entry.
“Many questions must be addressed before we can herald immunotherapeutic approaches to cancer an unqualified success,” said Collins. “There are still too many severe reactions, too many non-responses or relapses, and, potentially, a very high price tag for their widespread use, which will be truly challenging to scale up. But we’re off to a promising start.”
Mesothelioma is a cancer caused by past exposure to asbestos. Nearly 3,000 Americans are diagnosed with the terminal cancer each year.
Sources:
- August 30 press release
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm - NIH Director’s Blog
https://directorsblog.nih.gov/2017/08/30/fda-approves-first-car-t-cell-therapy-for-pediatric-acute-lymphoblastic-leukemia - mesothelioma clinical trial
https://clinicaltrials.gov/ct2/show/NCT01590472
Older Mesothelioma Patients “Less Likely” to Receive Treatment
Last week, MesotheliomaHelp reported on the benefits of mesothelioma patients receiving trimodal therapy. Now, in another study aimed at better understanding the patterns of mesothelioma care and the associated survival, researchers found a startling number of untreated mesothelioma patients in the U.S.
Researchers from the National Cancer Institute reviewed the data of mesothelioma patients, identified as such from the Surveillance, Epidemiology, and End Results (SEER) Program of the NCI. SEER provides information on cancer statistics in an effort to reduce the cancer burden among the U.S. population. The data backed findings that mutli-modal therapy is best, however, the researchers discovered that nearly one-third of U.S. mesothelioma patients do not receive cancer therapy.
The study reviewed records of 389 pleural mesothelioma patients and 53 non-pleural mesothelioma patients, all of who were diagnosed in 2011. The researchers highlight the following key points of the study:
- 29.3% of the pleural mesothelioma patients and 21.5% of the non-pleural patients do not receive cancer therapy.
- Older pleural patients [older than 70-years] were less likely to receive therapy.
- Median survival was 8 months among pleural mesothelioma patients and 18 months among non-pleural mesothelioma patients.
- Among pleural mesothelioma patients receipt of surgery and systemic therapy was associated with the best survival.
Further information showed that, not surprisingly, younger pleural mesothelioma patients had better survival. In addition, 60 percent of the patients received some form of systemic treatment, which includes chemotherapy and immunotherapy, although the older population was “less likely” to undergo the treatments.
Patients may refuse treatment for a variety of reasons, and understanding and respecting the wishes of a patient is important. Read how one nurse explains a “Mesothelioma Patients’ Treatment Plans Can Match Their Wants.”
Of concern to the team is the fact that with all the mesothelioma research being done to find an effective treatment, and potentially a cure for the now incurable cancer, nearly one-third of the patient population could be missing out on extended survival.
Expert Insight
Lindsey Enewold, PhD, MPH, NCI
“Our findings indicate that only a subset of mesothelioma patients realize the benefit of established treatment options.”
The researchers point out that clinical trials “offer the best hope of finding more effective treatments for mesothelioma,” yet still, less than 5% of pleural mesothelioma patients and less than 2% of the non-pleural mesothelioma patients actually participated in a trial.
“Expanding our understanding of the particular challenges to participation in clinical trials in mesothelioma is essential to making an impact on this disease,” reported the researchers.
“These findings indicate the need for efforts to ensure equitable application of currently available therapies to all patients,” concluded the authors.
According to the NCI, the major cause of malignant mesothelioma is exposure to asbestos, including people who were exposed to asbestos in the workplace and their family members. Development of mesothelioma from asbestos exposure via a loved one is called second hand exposure. Exposure to asbestos can lead to mesothelioma decades later. Nearly 3,000 Americans are diagnosed with mesothelioma each year.
Read the full study, “Patterns of care and survival among patients with malignant mesothelioma in the United States,” in the August 10 journal Lung Cancer.
http://www.lungcancerjournal.info/article/S0169-5002%2815%2900157-9/abstract
New Mesothelioma Treatment May Result From Study Focusing on The Deadliest Subtype of Lung Cancer
In February, MesotheliomaHelp reported on research from the Mayo Clinic that pointed to the Ect2 gene as a target to slow tumor growth in KRAS-positive lung cancer and mesothelioma patients. Now, in another study, researchers believe they have found one more way to fight this deadly sub-type of lung cancer.
Researchers from Norton Thoracic Institute, headquartered at Dignity Health St. Joseph’s Hospital and Medical Center in downtown Phoenix, focused their research on lung cancers expressing the KRAS and/or the LKB1 gene noting that these “mutations are associated with aggressive disease progression and poor patient prognosis, and have been historically difficult to treat.”
The team looked at the use of a WEE1 kinase inhibitor, AZD1775, an experimental drug from AstraZeneca available to researchers only, as an effective treatment in the KRAS or LKB1 expressed lung cancer population. The drug could lead to apoptosis, or cell death, upon treatment with chemotherapeutic agents such as gemcitabine, cisplatin, carboplatin, according to AstraZeneca.
The team found that in a mouse model with the KRAS/LKB1 NSCLC cell lines, the combination of AZD1775 and cisplatin extended overall survival compared with cisplatin alone. In mesothelioma and lung cancer patients, cisplatin is one of the most common chemotherapy treatments used. It is often used in combination with other chemotherapeutic agents.
“In this study, we highlight a therapeutic strategy that may be effective in a group of lung cancer patients without rational therapeutic options,” said Timothy Whitsett, PhD, assistant professor at Norton Thoracic Institute.
According to some reports, mutations of the KRAS gene (Kirsten rat sarcoma viral oncogene homolog) are found in 20 to 25 percent of lung cancers. These cancers do not respond well to standard treatments and are extremely challenging to treat. In a 2014 study conducted by Salk Institute researchers, the team found that lung cancer patients who have an alteration in the LKB1 gene had a “much greater rate” of metastasis.
Kinases function as drivers of a variety of forms of cancer, including mesothelioma. Many researchers have found that kinases are involved in the gradual transformation of normal tissue in the lining of the lung into malignant pleural mesothelioma after exposure to asbestos. Thus, the use of kinase inhibitors, such as AZD1775, should slow cancer growth.
Landon Inge, PhD, co-author and assistant professor, said, “We hope these findings spur new explorations for targeting this molecular subgroup, leading to better clinical trial design in the near future.”
The researchers plan to continue this research to identify patients “who will most likely benefit from the use of this type of therapy, and to inform future clinical trial design by selecting lung cancer patients with difficult to treat molecular alterations.”
Care for mesothelioma, a rare form of cancer caused by exposure to asbestos fiber, often follows the same protocol as lung cancer. Positive results in this study can mean positive results for mesothelioma patients. Approximately 3,000 Americans are diagnosed with mesothelioma each year. Currently, there is no known cure for the cancer.
Read the results of the study in the August 15 issue of Cancer Research.
Sources
- Cancer Research
http://cancerres.aacrjournals.org/content/early/2012/04/25/0008-5472.CAN-11-3481.abstract?sid=c98a9479-15e8-43da-8088-356c133a2536 - Mayo Clinic
http://newsnetwork.mayoclinic.org/discussion/mayo-researchers-identify-mechanism-of-oncogene-action-in-lung-cancer - Norton Thoracic Institute
https://www.dignityhealth.org/arizona/locations/stjosephs/about-us/press-center/press-releases/2017-08-18-researchers-discover-a-novel-therapeutic-strategy
Study Shows Pleural Mesothelioma Patients Live Longer With Trimodal Therapy
One of the biggest challenges in pleural mesothelioma care is determining which treatments to use on patients.
Oncologists are faced with deciding if a patient will benefit from surgery, chemotherapy or radiation, or a combination of the three.
Although each case is different, when mesothelioma patients are candidates for all of the options, which approach is the best?
Researchers report the results of a recent in-depth review of thousands of mesothelioma patient records points to the best survival when all three therapies are used.
A team of researchers from The University of Texas MD Anderson Cancer Center selected 20,561 malignant pleural mesothelioma (MPM) patient records, from the National Cancer Database for the years from 2004 to 2014, to evaluate patient survival. Noting that MPM is an “aggressive and rapidly fatal disease,” the team set out to determine the key predictors of mesothelioma patient survival.
Specifically, the team wanted to assess the difference in patients who first had mesothelioma surgery, then went on to have chemotherapy and/or radiation versus patients who did not have surgery.
The team narrowed the number of patients evaluated down to 6,645 from the initial selection and compared the results of patients with the following breakdown of treatment approaches:
- 2,166 underwent no therapy
- 2,015 underwent chemotherapy alone
- 850 underwent cancer-directed surgery alone
- 988 underwent surgery with chemotherapy
- 274 underwent trimodality therapy
The remaining 352 patients underwent another combination of surgery, radiation, or chemotherapy.
Although the researchers found that while any of the treatments alone were associated with improved survival, when chemotherapy and radiation followed cancer-directed surgery the” largest estimated effect was realized.”
Most importantly, patients diagnosed with epithelioid mesothelioma, the most common and treatable histological subtype of mesothelioma diagnosed in more than half of all mesothelioma cases, who received trimodal care had a median survival of 23.4 months vs. 14.5 months.
The team concluded that for mesothelioma patients, “Surgery-based multimodality therapy was associated with improved survival and may offer therapeutic benefit among carefully selected patients.”
MD Anderson’s Mesothelioma Program is comprised of a team of more than 30 experts representing medical oncologists, surgeons, radiation oncologists, pulmonologists and pathologists who work closely together to customize the best treatment for each patient.
Everyone on the team is considered an expert in their field and in mesothelioma. The Center cares for more patients with mesothelioma than almost any other center in the U.S., according to its website.
Read the full study in the Aug. 17 issue of Journal Of Clinical Oncology.
Could Locking Out a Protein Halt Development of Mesothelioma?
Given the staggering number of Americans who die each year from lung cancer, researchers from the University of Kentucky College of Pharmacy, Memorial Sloan Kettering Cancer Center, and St. Jude Children’s Research Hospital joined forces to find a way to turn those statistics around. The team may have done just that by discovering a way to block a protein that “leads directly to cancer formation.”
After more than 10 years of research, the team found that high levels of the DCN1 protein led to an increase in lung cancer cases, and in lung cancer patients the protein directly correlated to a shorter life span. They were determined to find a way to block that protein and stop it from leading to early death, according to a June 26 press release from the University of Kentucky.
The researchers realized they needed to get to DCN1’s partner protein, UBE2M, and intercept it before it underwent a small modification known as N-terminal acetylation, after which it would bind to DCN1 and control the formation of cancer. Previous studies have shown that DCN1 promotes some squamous cell head, neck and lung cancers.
They were able to develop a compound that kept the DCN1 protein isolated and safe from the modified UBE2M. Likening the result to a lock and key system, if UBE2M was the key, and DCN1 was the lock, the compound, in effect, jammed the lock and stopped the key from entry. Further testing found the compound “effectively blocked DCN1 from binding to UBE2M.”
“To have spent decades on this research and have such promising results is truly exhilarating,” said Dr. Bhuvanesh Singh, a physician-scientist at Memorial Sloan Kettering Cancer Center, who laid the groundwork for the research.
Expert Insight
Dr. Bhuvanesh Singh
“This work represents a very important step towards developing a new approach to treat the most difficult of cancers and hopefully increase cure rates.”
When teams from some of the greatest cancer research centers in the U.S. get together, there are bound to be groundbreaking results. The collaboration between these three labs, according to the press release, “could mean relief to many of those suffering from a variety of diseases.”
As with all breakthrough research for lung cancer, the mesothelioma community takes notice. Pleural mesothelioma is an asbestos-caused cancer of the lining of the lungs that is very aggressive, much like lung cancer, and fights off some of the strongest cancer-fighting agents. Prognosis is often less than one year for patients. However, finding a way to attack cancer growth agents, such as with this research, could mean increased survival for mesothelioma patients.
Lung cancer is the leading cause of cancer death in men and women with an estimated 222,500 new diagnoses and 155,870 deaths in 2017, according to the National Cancer Institute. According to the UK researchers, Kentucky leads the nation in incidence and death rates from lung cancer. Kentucky ranks 30th in number of deaths from mesothelioma. Nearly 3,000 Americans are diagnosed with mesothelioma each year.
“We are excited about the implications of this research, which offer us a meaningful solution for addressing diseases like cancer, neurodegenerative disorders, and infection,” said Brenda Schulman, PhD, Joseph Simone Chair in Basic Research, St Jude Children’s Research Hospital HHMI, Investigator.
See the full study in the June 5 issue of the journal Nature Chemical Biology.
http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.2231.html
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