Category: Mesothelioma
Protein Identified As Target to Halt Spread of Mesothelioma and Other Cancers
Time and again mesothelioma patients discover that while their cancer treatment initially appeared effective, cancer cells slipped away and spread to other areas of their body. It is this metastasis that eludes scientists. Now, researchers report they have identified a protein they can target that will prevent the spread of cancer cells.
The LTBP3 protein, known to fuel blood vessel growth, in effect, spurs cancer cells to spread beyond the initial tumor site by traveling in these new “highways” through the body, according to a Feb. 16 press release from the Scripps Research Institute. Patients who had lower levels of this protein had a better prognosis, leading the researchers to focus on finding a way to target LTBP3.
The research team looked more closely at LTBP3 and TGFβ, a molecule that has been linked to both growth and suppression of cancer. They knew the two “partner” to regulate TGFβ, but they wanted to find if the two worked in concert to spread cancer. However, because TGFβ is both good and bad, they had to find a way to suppress the molecule’s harmful effects, without interfering with the benefits for slowing cancer growth.
Using chick embryo and mouse models, they suppressed LTBP3 and discovered that without it, primary tumor cells could not metastasize efficiently. This indicated that LTBP3 is involved very early in the metastasis process. The team concluded “LTBP3 levels can indicate better overall survival” in some cancer patients.
The team reports that LTBP3 is a good “upstream” drug target for early stage tumors without affecting the role of TGFβ. Their next step is to determine how LTBP3 and TGFβ partner in the induction of new blood vessels deep within a tumor.
Finding a way to halt the spread of deadly cancer cells is critical for improving survival in mesothelioma patients. In fact, according to the American Cancer Society, “With upwards of 90% of all cancer suffering and death associated with metastasis, it is the single most significant challenge to management of the disease.”
Nearly 3,000 Americans are diagnosed with mesothelioma each year. Finding an effective way to stop the cancer from spreading, as opposed to treating the cancer after it has spread, brings hope to the mesothelioma community.
Find out more about the Scripps study in the January 19 issue of Oncogene.
Sources:
- January 19 issue of Oncogene
https://www.nature.com/articles/s41388-017-0075-1
- Scripps Research Institute
https://www.scripps.edu/newsandviews/e_20180216/deryugina.html
Mesothelioma Patients Eye Combination Therapy Given FDA Priority Review for Bringing “Significant Survival Benefit” To Lung Cancer Patients
In October 2016, MesotheliomaHelp reported the U.S. Food and Drug Administration approved the immunotherapy drug atezolizumab (TECENTRIQ, Genentech Oncology) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose disease progressed after platinum-based chemotherapy. Now, Genentech reports the FDA has granted priority review for Tecentriq when used in combination with bevacizumab (Avastin), paclitaxel and carboplatin (chemotherapy), for lung cancer patients.
The status was given based on results from the Phase III IMpower150 study, according to the May 6 press release from Genentech announcing the approval. The trial was established to evaluate the safety and efficacy of Tecentriq with the triple drug combination compared with patients receiving the triplet without Tecentriq. Tecentriq is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells and to enable the activation of T cells, according to the company.
“Our Phase III results showed TECENTRIQ in combination with Avastin, paclitaxel and carboplatin has the potential to provide a significant survival benefit in the initial treatment of metastatic non-squamous non-small cell lung cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are working closely with the FDA to bring this treatment regimen to people with this type of lung cancer as soon as possible.”
Lung cancer is by far the leading cause of cancer death among both men and women in the U.S., according to the American Cancer Society. The ACS estimates about 234,030 new cases of lung cancer will be diagnosed in 2018, with approximately 154,050 Americans dying from the cancer. Nearly 3,000 Americans are diagnosed with mesothelioma, with close to the same number losing their lives to it each year.
Pleural mesothelioma is an asbestos-caused cancer affecting the lining of the lungs. Although there are clinical differences between lung cancer and mesothelioma, the treatment protocol for the two cancers are similar. Mesothelioma is a terminal cancer with limited treatment options. Any new breakthrough or approval in the treatment of NSCLC is considered a win for mesothelioma patients as well.
A Priority Review designation will direct overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications, according to the FDA.
https://www.fda.gov/ForPatients/Approvals/Fast/ucm405405.htm
A Priority Review designation means FDA’s goal is to take action on an application within 6 months. Genentech reports the FDA is expected to make a decision on approval by September 5, 2018.
Find out more about the IMpower150 clinical trial at ClinicalTrials.gov.
https://clinicaltrials.gov/ct2/show/NCT02366143
Sources :
- Genentech
https://www.gene.com/media/press-releases/14715/2018-05-06/fda-grants-priority-review-to-genentechs - American Cancer Society
https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html
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/
ASCO Offers Malignant Pleural Mesothelioma Treatment Guidelines
The American Society of Clinical Oncology (ASCO) is the world’s leading professional organization for medical professionals caring for cancer patients. The Society has a goal to improve the quality of care in the field of oncology. Now, to assist medical professionals managing patients with malignant pleural mesothelioma, the organization has just released new evidence-based recommendations.
In their newly released clinical practice guidelines, ASCO offers guidelines for diagnosis, staging, chemotherapy, surgical cytoreduction, radiation therapy, and multimodality therapy in malignant pleural mesothelioma (MPM) patients. According to the panel of experts, including Hedy L. Kindler, MD, of the University of Chicago, and Mary Hesdorffer, formerly the Executive Director of the Mesothelioma Applied Research Foundation, the recommendation addresses five “overarching clinical questions.”
- What is the optimal approach to obtain an accurate diagnosis of mesothelioma?
- What initial assessment is recommended before initiating any therapy for mesothelioma?
- What is the appropriate first- and second-line systemic treatment of patients with mesothelioma?
- What is the appropriate role of surgical cytoreduction in the management of mesothelioma?
- When should radiation be recommended for mesothelioma?
Pleural mesothelioma is a rare, painful cancer caused by exposure to airborne asbestos fibers. Treatments manage the symptoms to hold the cancer at bay, but there is no known cure for this deadly disease. Patients have a poor prognosis, and the median overall survival of patients with advanced surgically unresectable disease is about 12 months, according to ASCO. About 3,000 new cases are diagnosed each year in the U.S.
The ASCO team noted that “Given the rarity of this malignancy, there have been few large randomized trials, especially for surgical management of this disease.” Seeing a critical need to find and compile this information, ASCO convened a panel of experts, including thoracic, oncology and advocacy experts, to review medical literature published from 1990 through 2017 that included references to pertinent trials and studies.
Through the search of the literature, the team identified 222 relevant studies. After assessing the key areas of interest, including survival and quality of life, using evidence and informal consensus the team developed the evidence-based guideline recommendations.
The guidelines, published in the Journal of Clinical Oncology, include offering chemotherapy as a means for improving survival and quality of life for mesothelioma patients. The recommended first-line chemotherapy is pemetrexed plus platinum. However, the team recommends offering patients the option of enrolling in a clinical trial. Other chemotherapy recommendations include the addition of bevacizumab to pemetrexed-based chemotherapy for select patients, as well as pointing out risks for the use in some patients.
The panel “strongly recommends” a maximal surgical cytoreduction surgery for certain patients with early-stage disease. The recommendations note, however, that surgery is just one modality and chemotherapy and/or radiation should also be administered.
See the Journal of Clinical Oncology for all of the mesothelioma recommendations.
ASCO states that “clinical practice guidelines are intended to improve the quality of cancer care by helping oncologists make choices about treatment, prevention, supportive care, or follow-up in line with the best available evidence from oncology research.” ASCO notes that the guidelines are voluntary and do not account for variation among patients or the most recent evidence.
Sources:
- ASCO
https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/thoracic-cancer#/29376 - Journal of Clinical Oncology
http://jco.ascopubs.org/content/early/2012/12/13/JCO.2012.44.6443.abstract
Breakthrough Blood Test May Extend Mesothelioma Survival
Just last week, MesotheliomaHelp reported on a corporate partnership for blood test tools that will bring improved results in the detection of key lung cancer mutations. Blood biopsies are shown to be fast and accurate, as well as less stressful on the patients. Now, in another breakthrough using liquid biopsies, researchers report success in the early detection of mesothelioma and screening for multiple cancers using one tool.
Researchers from Johns Hopkins University have developed the CancerSeek blood test that is able to screen for eight different types of cancers and can help pinpoint the location of the tumor. In a recent study of 1,005 cancer patients, the results had a “greater than 99 percent specificity for cancer,” according to a Jan. 19 press release from Johns Hopkins University.
[expert_info author=”Bert Vogelstein, Johns Hopkins University”]”This test represents the next step in changing the focus of cancer research from late-stage disease to early disease, which I believe will be critical to reducing cancer deaths in the long term.”[/expert_info]Although there are screening options for some cancers, such as breast and prostate, mesothelioma, and many other cancers, are diagnosed after the patient goes to a doctor exhibiting some of the signature symptoms of cancer: unexplained weight loss, extreme fatigue and a persistent cough. CancerSeek results had a sensitivity ranging from 69 percent to 98 percent in five cancers that do not currently have any screening test availables, including ovarian, pancreatic, and esophageal cancers.
The test, according to the researchers, looks at eight common cancer proteins and the presence of cancer gene mutations from DNA circulating in the blood. The team developed a “small yet robust panel” that could detect at least one mutation and not lead to false-positives. The test is used for cancer detection only, and does not detect specific biomarkers to drive treatment.
“The use of a combination of selected biomarkers for early detection has the potential to change the way we screen for cancer…,” says Nickolas Papadopoulos, senior author and professor of oncology and pathology at Johns Hopkins.
Pleural mesothelioma, a deadly cancer of the lungs caused by past exposure to asbestos, has a long incubation period where patients may not exhibit symptoms for decades after exposure. By then the disease is already at an advanced, incurable stage.
Early detection of cancer through screening reduces mortality from many cancers, including lung and colon, according to the National Cancer Society. When treating mesothelioma patients, the best outcome is achieved with early detection of the disease by increasing treatment options and improving the patients’ quality of life while battling the cancer.
The tests are still in the early stages of research and are not yet available; however, they may be helpful in diagnosing mesothelioma in the future. In fact, the team anticipates a relatively inexpensive test that may be conducted by a primary care provider.
Read the results of the study in the Jan. 18 issue of the journal Science.
http://science.sciencemag.org/content/357/6349/378
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