Mesothelioma Treatment from Aggressive Lung Cancer

Mesothelioma Treatment May Come From Discovery of Treatment for “Undruggable” Form Of Aggressive Lung Cancer

MesotheliomaHelp has reported many times on the challenges in treating KRAS-positive lung cancer, one of the most aggressive subtypes of lung cancer. Now, in a new study, researchers report they may have found a way to tackle lung cancer when the KRAS gene is present. This finding could also prove encouraging in the future for mesothelioma treatment.

According to an Oct. 2 press release in MIT News, a team of MIT researchers took a closer look at the Kirsten rat sarcoma virus (KRAS) and homed in on the KEAP1 mutation of KRAS, which, according to the researchers, is the third most frequently mutated gene in lung cancer. They found that in cancer where the KEAP1 gene is “nonfunctioning” cancer cells hunger for glutamine. They determined that if they could cut off the supply of glutamine to the tumors, they could treat both KRAS and KEAP1 mutations.

KRAS-mutated cancers are referred to as “undruggable” due to the inability to successfully target the protein with medicine. However, the MIT researchers began to experiment with suppressing KEAP1 which resulted in over-expression of yet another protein, NRF2, becoming hyperactive. This led them to then assess NRF2, and they determined that patients with “‘up-regulated’ NRF2 tumors had significantly worse survival rates” than other lung cancer patients.

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Tyler Jacks, MIT

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The team then turned back to KEAP1 and focused on its need for glutamine, finding that in lung cancer cells with loss-of function mutations for both KRAS and KEAP1 the cells were more dependent than others on increased amounts of glutamine. Using inhibitors of glutaminase, an enzyme crucial to glutamine metabolism, in these cells slowed cancer cell growth and shrunk lung cancer tumors.

The KRAS/KEAP1 mutations can occur in 17 percent of lung cancer patients, according to the researchers. Various studies have found KEAP1 mutations in malignant mesothelioma cells, with one study finding it active in seven percent of the pleural mesothelioma tissue samples.

“The genetic tools that we have assembled allow us to create models of many individual subtypes of the disease [cancer] and in this way begin to define the exploitable vulnerabilities of each,” said Tyler Jacks, director of MIT’s Koch Institute for Integrative Cancer Research and co-senior author of the study. “The observed sensitivity of KEAP1 mutant tumors to glutaminase inhibitors is an important example of this approach. There will be more.”

The KRAS gene is also found in some pleural mesothelioma patients. Mesothelioma, a rare form of cancer caused by exposure to airborne asbestos fibers, is highly aggressive and is resistant to many current treatments. Care often follows the same protocol as lung cancer. As a result, mesothelioma patients struggling to find effective treatments for the incurable cancer stand to benefit greatly from this research.

The good news in this research is that one of the inhibitors used, CB-839, is already in phase I clinical trials for both KEAP1-mutant and KRAS-mutant lung cancer patients. This study might help identify appropriate patients for these trials.

The American Cancer Society estimates about 222,500 new cases of lung cancer and nearly 155,870 deaths from lung cancer in the U.S. in 2017. Close to 3,000 Americans will be diagnosed with mesothelioma this year with nearly the same number dying from the terminal cancer.

Molecule Determines Lung Cancer Cells - Mesothelioma Cells

Molecule That Determines Fate of Lung Cancer Cells May Do the Same For Mesothelioma Cells

microRNAs are critical to cancer researchers, specifically in leading them to a breakthrough in the diagnosis or treatment of cancer. Research has shown that miRNAs, single stranded molecules that regulate gene expression, can be a key driver in the development of cancer. Now, researchers believe they can also be the key to killing off cancer cells.

In an important new study published this month in Science Signaling, researchers from the Boston University School of Medicine (BUSM) looked at KRAS mutant non–small cell lung cancer (NSCLC) based on its two subtypes, epithelial and mesenchymal. They found that while mesenchymal NSCLCs are less responsive than epithelial NSCLCs to inhibition of the RAS pathway, mesenchymal tumor cells are especially sensitive to miR-124.

When there was a loss of miR-124 in the mesenchymal tumor cells there was an increase in cell survival. On the other hand, when there was an overexpression of miR-124, apoptosis, or cell death, was triggered. This finding led the researchers to conclude that miR-124 can be an alternative molecular target for treating the mesenchymal subtype of NSCLC.

“Understanding the mechanisms that are associated with phenotypic heterogeneity in lung cancer cells–specifically differences between epithelial and mesenchymal-like cells–allows these differences to be exploited to develop more selective therapeutic agents,” said corresponding author Anurag Singh, PhD, assistant professor of pharmacology and medicine at BUSM, in a press release announcing the findings.

Mesothelioma is a cancer associated with asbestos exposure that affects the lining of the lungs or abdomen. It is an aggressive cancer that is often resistant to chemotherapy and radiation treatments. However, mesothelioma patients and lung cancer patients often undergo the same treatments making this finding important to mesothelioma care. In the United States, nearly 3,000 new cases of mesothelioma are diagnosed each year.

The researchers used what they call mesenchymal-like cells that had undergone a switch known as epithelial to mesenchymal transformation. Other studies have shown the epithelial to mesenchymal transition in mesothelioma cells, suggesting the potential for using microRNAs in innovative treatment therapies to suppress tumor growth in lung cancer and malignant mesothelioma patients.

The mesenchymal-like cells are resilient and fight off chemotherapy agents that should lead to their death. However, when the researchers looked more closely at the role miR-124 had on the cancerous cells, it was an indicator of whether the cancer cells would respond to chemotherapy, according to Medical News Today.

Targeted therapy for mesothelioma and lung cancer patients optimizes the potential for success of the treatment and offers treatment options that may not otherwise have been considered. Every new breakthrough in cancer research brings hope to mesothelioma patients. Although the rare cancer is terminal, each significant finding brings a cure one step closer.

The BUSM researchers hope their discovery leads to clinical trials for NSCLC patients, however, they point out that “additional work must be done to explore this possible therapeutic target.”

Read the full study in the September issue of Science Signaling.

Sources:

Science Signaling
http://stke.sciencemag.org/content/9/450/rs12
(University School of Medicine) BUSM
https://www.bumc.bu.edu/busm/2017/09/12/researchers-identify-possible-new-target-in-fight-against-lung-cancer/
Medical News Today
http://www.medicalnewstoday.com/releases/313580.php

Unexpected Results in Experiment Could Lead To Mesothelioma Killer

Craig Meyers didn’t set out to find a cancer killer, but as experiments go, you don’t always get what you expect. In this case, in 2008 he and his assistant were conducting an experiment using a little known virus to fight HPV, when unexpectedly, all of the HPV cells died. Now, he is hoping to continue his research that has shown promise in killing other types of cancer – including mesothelioma – to find a new anti-cancer treatment.

After discovering that the adeno-associated virus type 2 virus (AAV2), known to infect humans but not known to cause sickness, actually led HPV (human papillomavirus) cancer cells to kill themselves, Craig Meyers, Penn State Distinguished Professor of Microbiology and Immunology and BYU alumnus, immediately began using AAV2 against multiple other cancer lines, including mesothelioma cells, according to the Summer 2017 issue of BYU Magazine. Meyers was once again shocked when he found that all these cancer cells also died.

“We . . . collected different cancer cell lines—breast cancer, prostate cancer, squamous cell carcinoma, melanoma, and mesothelioma cells,” he says. “We tested them all, and [AAV2] worked in them all,” said Meyers.

Myers has spent his time since 2008 trying to better understand why AAV2 kills cancer cells, although he says, “That’s the million-dollar question,” and upgrading his tests from petri dishes to mouse models. The next step is human testing.

The fact that Myers had success against mesothelioma lines brings hope that an effective treatment could be available to mesothelioma patients in the future. The asbestos-caused cancer, that strikes close to 3,000 Americans each year, is incurable and leaves many patients with a poor quality of life.

Myers has spent his career trying to find a successful treatment for HPV, a sexually transmitted disease, that can lead to cervical cancer. When his “accidental” discovery led him to realize that AAV2 led the HPV cancer cells to apoptosis, he began his work to bring this breakthrough to helping all cancer patients.

“Until I can get to this last set of trials, I have to caution people . . . that we don’t have a cure yet and at any step this could just stop working. That’s always the nightmare.”

Investigational Drug Effective in Treatment of Pleural Mesothelioma

In January, MesotheliomaHelp reported that the U.S. Food and Drug Administration granted orphan drug designation to Boehringer Ingelheim’s investigational drug nintedanib for the treatment of mesothelioma. Now, in the announcement of clinical trial results at the International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology, the company reports the drug has been found to be “safe and effective” treatment for patients with pleural mesothelioma.

The phase II/III trial, known as the LUME-Meso trial, is designed to evaluate nintedanib (BIBF 1120) when combined with the chemotherapy duo pemetrexed / cisplatin for the treatment of patients with unresectable malignant pleural mesothelioma. The results of 87 patients in the trial, showed that the 44 treated with nintedanib demonstrated improved progression free survival (PFS) and a trend for prolonged overall survival (OS). In addition, patients with epithelioid malignant pleural mesothelioma, the most common and most treatable subtype, experienced the “greatest benefit from nintedanib treatment” with a PFS of 9.7 months vs. 5.7 months, and OS of 20.6 months vs. 15.2 months.

Currently, the standard of care for pleural mesothelioma is the combination chemotherapy of pemetrexed and cisplatin.

“Nintedanib strongly inhibits malignant pleural mesothelioma tumor growth in human xenograft models and reduces the colony-forming capacity and migratory activity of malignant pleural mesothelioma cell lines,” said José Barrueco, executive director of global clinical development of oncology at Boehringer Ingelheim, as reported in HemOnc Today. https://www.healio.com/hematology-oncology/lung-cancer/news/online/%7Bfef3c4aa-ac73-4940-b8ef-2834a95e0427%7D/nintedanib-shows-promise-for-malignant-pleural-mesothelioma?page=2

According to Boehringer Ingelheim, the maker of nintedanib, the drug is an oral triple angiokinase inhibitor which simultaneously inhibits vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR) and fibroblast growth factor receptors (FGFR 1-3) signaling pathways.

“The safety profile was manageable and consistent with previous nintedanib studies, and it did not compromise delivery of the backbone chemotherapy,” Barrueco said.

Talk to your oncologist to find out if you are a candidate for the trial. Mesothelioma patients are currently being recruited worldwide, including in the U.S., Australia and Canada, for the trial. To find out more, see ClinicalTrials.gov. https://clinicaltrials.gov/ct2/results?term=%22malignant+mesothelioma%22&recr=Open&pg=1

September 26 Is National Mesothelioma Awareness Day

Each year, the mesothelioma community across the nation comes together for Mesothelioma Awareness Day, a time devoted to raising public awareness about the life-threatening cancer and its cause ─ exposure to asbestos.

Patients, family members, friends, advocates and health care professionals are encouraged to share their personal stories, struggles and inspiration in order to bring attention to the disease and further the search for a cure.

When Is Mesothelioma Awareness Day?

Mesothelioma Awareness Day is held on Sept. 26. In 2018, September 26 falls on a Wednesday.

In an effort to expand the impact of Mesothelioma Awareness Day, advocates have encouraged patients, caregivers, family and friends to participate in Mesothelioma Awareness Week surrounding Sept. 26, as well as Mesothelioma Awareness Month throughout September.

Mesothelioma Awareness Day History

In 2004, the Mesothelioma Applied Research Foundation organized the original Mesothelioma Awareness Day. Since then, the national nonprofit organization has continued to build momentum by promoting the day as a time for all those touched by the cancer to talk about its impact.

In 2010, Congress joined the effort by establishing Mesothelioma Awareness Day as a time for the nation to recognize that thousands of Americans are diagnosed with the preventable cancer each year. In fact, despite its designation as a known carcinogen, asbestos is still not banned in the United States, and Americans are still at risk of exposure.

The Importance of Awareness Day

The National Mesothelioma Awareness Day resolution asks that the President of the United States issue a proclamation calling for all Americans, federal agencies and departments, state governments, local municipalities, organizations, and news media to properly observe the day.

The Congressional Declaration outlines these key facts about malignant mesothelioma as reasons for promoting awareness of the deadly asbestos cancer:

Although workers who were exposed to asbestos on a daily basis over a long period of time are most at risk of developing mesothelioma, even short-term exposures can cause the disease. In fact, exposure to asbestos for as little as one month can result in mesothelioma 20 to 50 years later.
Asbestos materials were used in the construction of virtually all office buildings, public schools, and homes built before 1975. Still today, asbestos is used in more than 3,000 products being sold in the United States.
The National Institutes of Health reported to Congress in 2006 that mesothelioma is a difficult disease to detect, diagnose and treat.
For decades, the need to develop treatments for mesothelioma was overlooked. Still today, even the best mesothelioma treatments usually have a very limited effect, with the expected survival time of 8 to 14 months.
It is believed that many of the firefighters, rescue workers and police officers from Ground Zero on September 11, 2001, may be at increased risk of developing mesothelioma in the future due to asbestos exposure at the site.

Every year, about 3,000 people in the United States are diagnosed with mesothelioma. Around the world, an estimated 38,400 people die each year from the devastating asbestos illness.

Unfortunately, those numbers are not dwindling. Mesothelioma statistics indicate an increase in deaths in recent years, with an 8 percent increase in fatalities in the United States for the 10-year period that ended in 2015.

These facts point to the importance of Mesothelioma Awareness Day in educating people about the dangers of asbestos and promoting the need for continued research into more effective treatments.

Paint the World in Mesothelioma Awareness

Just as breast cancer is associated with the color pink, support for mesothelioma awareness is often represented by a colored ribbon. The mesothelioma awareness color is blue or pearl.

Friends and family members of patients typically don pearl or blue ribbons in a show of solidarity with their loved ones who are fighting the life-threatening disease.

The Mesothelioma Applied Research Foundation also encourages people to participate in its “Paint the World in Mesothelioma Blue” campaign to raise awareness by wearing blue and sharing photos of themselves on social media.

How You Can Show Support on Mesothelioma Awareness Day

Since its founding, the nonprofit Mesothelioma Applied Research Foundation has advocated for patients and families while coordinating fundraising events to support research efforts related to the disease. This national organization is committed to finding a cure for mesothelioma and ending the suffering it causes.

One way to show your support on Mesothelioma Awareness Day is to make a donation to the Meso Foundation. Your contribution will help fund the organization’s efforts to support mesothelioma patients and the ongoing search for a cure.

You may also choose to show your support by wearing (and asking others to wear):

Mesothelioma awareness ribbons
Mesothelioma awareness pins
Mesothelioma awareness bracelets
Mesothelioma awareness wristbands
Mesothelioma awareness shirts

At Mesothelioma Help Cancer Organization, we aim to raise awareness year-round, in particular through our Mesothelioma Awareness Scholarship Contest. As part of this contest, students submit essays sharing their own experiences with mesothelioma as well as their efforts for raising awareness of the dangers of asbestos. We encourage the students to share their essays on social media to help spread the word.

Quick Facts to Share on Mesothelioma Awareness Day

Asbestos is the only known cause of mesothelioma. It has also been shown to cause lung cancer.
Asbestos was commonly used on Navy ships and in shipyards. Veterans account for approximately one-third of mesothelioma diagnoses.
Industrial workers and construction workers are at an increased risk of developing mesothelioma and other asbestos diseases.
Family members of those who worked with asbestos may have faced secondhand exposure through fibers brought home on clothing or skin.
Although the U.S. government has safety regulations in place, it has not banned the use of asbestos.
There is no safe level of asbestos exposure.
Renovation projects on older homes and demolition of older buildings can put people at risk of asbestos exposure.
Never try to remove asbestos materials on your own. Contact an asbestos abatement professional.
Companies that made asbestos products understood the health risks but failed to warn the public.
Mesothelioma patients and families may be entitled to compensation for damages due to asbestos exposure.
Even if an asbestos company has gone out of business, funds may be available in a bankruptcy trust for mesothelioma victims.