Category: Pleural Mesothelioma
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.
- University of Texas Southwestern Medical Center
- Mesothelioma program’s website
- UT Southwestern Medical Center
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.
- Journal of Clinical Oncology
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.
Combination of Liquid Biopsy Tools Improves Results in Detecting Biomarkers, May Lead to Better Selection of Targeted Mesothelioma Treatments
Researchers continue to look for an effective tool that can be used for the early detection of cancer and to track the effectiveness of treatment. Now, one company reports that by pairing its liquid biopsy analyzer tool with another company’s genetic data analysis tool, the resulting tests proved to be nearly 100% accurate. This is another step in using blood tests to help guide personalized medicine for lung cancer and pleural mesothelioma patients.
In a press release prior to the Fifth AACR-IASLC International Joint Conference held earlier this month in San Diego, Biocept, Inc, reports when it paired the Target Selector ctDNA lung cancer assays with the Thermo Fisher QuantStudio5 (QS5) real-time PCR instrument results of the detection of key lung cancer mutations resulted in “more than 99% sensitivity and more than 99% specificity.”
“The ability to rapidly and accurately assess the molecular status of a patient’s tumor using a simple blood draw can be a critical factor in the selection of individualized targeted therapy,” said Biocept’s Senior Vice President and Senior Medical Director Veena Singh, MD. “Our tests can further provide for the monitoring of response to therapy over time without invasive tissue biopsies that can be difficult to perform in patients diagnosed with cancer.”
The tests targeted EGFR, KRAS and BRAF mutations that have been shown to be present in lung cancer and in some pleural mesothelioma tumors as well. 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. The EGFR gene is overexpressed in more than 50% of pleural mesothelioma patients, and in approximately 15% of lung cancer patients, and is one of the primary targets for bringing personalized care to cancer patients.
With the advent of personalized therapies that target specific biomarkers, ensuring that effective tools are available to quickly and easily identify treatable mesothelioma markers is critical. Personalized cancer treatment optimizes the potential for success.
Often, lung cancer and mesothelioma patients must undergo invasive and painful biopsies to extract diseased tissue for diagnosis. Tissue biopsy tests can take up to 10 days to get a result leaving patients worried and missing out on treatment. However, with just a blood sample, this partnership could bring effective treatments to cancer patients in a shorter time.
Pleural mesothelioma, caused by exposure to airborne asbestos fibers, is an incurable cancer involving the lining of the lung. Nearly 3,000 Americans are diagnosed with mesothelioma each year. There is no cure for the cancer.
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.
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