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Month: June 2017

Mesothelioma Growth Linked to Density of Cancer Cells

Mesothelioma Growth Could be Linked to Density of Cancer Cells

As MesotheliomaHelp has reported time and again, the spread of cancer cells, or metastasis, is the biggest challenge for researchers when searching for effective treatments. It is this migration of the cancer cells, according to the National Cancer Society, that is the cause of 90 percent of all cancer deaths. Stopping this spread is critical for improving survival in mesothelioma patients. Now, researchers report they have found the reason cancer cells split off from the primary site, and more importantly, they may also know how to stop the process.

In a May 26 press release from Johns Hopkins, lead researcher Hasini Jayatilaka, a postdoctoral fellow at Johns Hopkins’ Physical Sciences-Oncology Center, found that it is not the overall size of a tumor that leads to metastasis, rather “how tightly those cells are jammed together” that has them break away. Jayatilaka likened the process to waiting for a table in an overcrowded restaurant but then deciding to go elsewhere or moving to the suburbs from the crowded city.

Cancer cells metastasize because they can reproduce quickly and they can get into the bloodstream where they then spread to other organs. When looking deeper into those processes, the team found that when the tumors became “more crowded” the cells secreted proteins that “encouraged migration.” The proteins, Interleukin 6 (IL-6) and Interleukin 8 (IL-8), sent signals basically telling the cancer cells to leave the primary tumor site.

“We found that it was not the overall size of a primary tumor that caused cancer cells to spread, but how tightly those cells are jammed together when they break away from the tumor,” said Jayatilaka. “At a fundamental level, we found that cell density is very important in triggering metastasis.”

When the researchers used two existing drugs at the tumor site, one approved for treating arthritis and the other being tested for breast cancer treatment, the receptors were blocked from receiving those signals, effectively halting the metastasis. Although the growth at the primary tumor site did not stop, the spread of the cancer cells was limited. This helped confirm that by blocking the signaling pathway, they could slow metastasis.

Expert Insight

Dr. Denis Wirtz, Johns Hopkins

“This treatment has the potential to inhibit metastasis and thus improve cancer patient outcomes.”

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“In our eight-week experiment, when we used these two drugs together, the growth of the primary tumor itself was not stopped, but the spread of the cancer cells was significantly decreased,” Jayatilaka said. “We discovered a new signaling pathway that, when blocked, could potentially curb cancer’s ability to metastasize.”

Once mesothelioma cells spread to distant regions of the body, the cancer, caused by past asbestos exposure, becomes virtually impossible to eradicate. Getting a handle on the spread of cancer is critical for increasing survival.

“The pharmaceutical companies view metastasis as a by-product of tumor growth,” said Denis Wirtz, Johns Hopkins University’s vice provost for research and director of its Physical Sciences-Oncology Center, and one of the study’s senior authors. “Our study looked more closely at the steps that actually initiate metastasis. By doing this, we were able to develop a unique therapeutic that directly targets metastasis, not the growth of the primary tumor.”

This drug cocktail was tested on mice in the lab, but has not yet been tested on humans. Wirtz said the feedback they have gotten from other researchers has been positive and others see “real potential for this approach.”

Mesothelioma, an asbestos-caused cancer is diagnosed in close to 3,000 Americans each year. There is no cure for the asbestos-caused cancer.

See the full study in the May 26 online issue of Nature Communications.

 

Sources:

  • Nature Communications
    http://www.nature.com/ncomms/2016/160524/ncomms11734/full/ncomms11734.html
  • Johns Hopkins
    http://releases.jhu.edu/2017/05/26/new-cellular-target-may-put-the-brakes-on-cancers-ability-to-spread/
Companies Join Together for Mesothelioma Cause

Companies Join Forces to Combat Mesothelioma

In November, MesotheliomaHelp reported on the encouraging results with the experimental cancer drug known as CRS-207 in its ongoing Phase 1b trial. Now Aduro Biotech, the maker of CRS-207, is joining forces with Merck, the pharmaceutical company that markets the immunotherapy drug Keytruda (pembrolizumab), to determine whether the combination of the two medications is effective in the treatment of malignant pleural mesothelioma.

Pleural mesothelioma is the signature cancer of asbestos that attacks the linings of the lungs. Although recent breakthroughs in treatment have improved the life expectancy for some patients, the prognosis for patients is poor with survival often less than 18 months. New, effective treatments are critical to bring hope to the mesothelioma community.

According to a May 17 press release from Aduro Biotech announcing the collaboration, based on the results of the company’s Phase 1 mesothelioma trial, and those of other studies that have shown positive results with the combination therapy, the companies are moving forward with the Phase 2 trial.

“Data from our ongoing Phase 1 clinical trial of CRS-207 with standard chemotherapy as frontline treatment for malignant pleural mesothelioma have been very encouraging,” said Natalie Sacks, M.D., chief medical officer at Aduro. “… we look forward to initiating a Phase 2 trial to evaluate the CRS-207/pembrolizumab combination in patients with malignant pleural mesothelioma who have failed prior treatment.”

The Phase 2 trial is currently recruiting patients with a goal to enroll 35 mesothelioma patients whose cancer has continued to progress despite undergoing one or two prior anti-cancer therapies. The trial, that has an estimated completion date of March 2019, is an extension of a collaboration between the two companies testing the same combination of drugs in gastric cancers.

According to Aduro Biotech, CRS-207 is a Listeria-based vaccine that has been engineered to stimulate an immune response to mesothelin, which is over-expressed in many cancers, including mesothelioma. According to one study, more than half of the mesothelioma patients at diagnosis had significantly elevated levels of mesothelin in their blood.

Keytruda, an immunotherapy drug from Merck that awakens the immune system to effectively fight off cancer cells, has been approved in the U.S. for use in melanoma and lung cancer patients after a prior round of chemotherapy failed to stop progression of the disease. Keytruda works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). Most recently, the U.S. Food and Drug Administration has granted accelerated approval to Keytruda as a treatment based solely on the genetic mutations of a cancer and not on the type of cancer.

The CRS-207/pembrolizumab mesothelioma trial will take place at various centers across the U.S. Currently, the Moffitt Cancer Center in Tampa, FL and University of Chicago Medical Center are recruiting patients. Mesothelioma patients should talk to their oncologist to determine if this trial might be right for them.

To find out more about the collaborative trial using CRS-207 and Keytruda see ClinicalTrials.gov.

https://clinicaltrials.gov/ct2/results?term=%22malignant+mesothelioma%22&recr=Open&pg=1

 

Sources:

  • Aduro Biotech
    http://investors.aduro.com/phoenix.zhtml?c=242043&p=irol-newsArticle&ID=2273583
  • U.S. Food and Drug Administration
    http://www.mercknewsroom.com/news-release/oncology-newsroom/merck-announces-fda-acceptance-review-mk-3475-biologics-license-appli
FDA Approval of Anti-Cancer Drug

First-Ever FDA Approval of Anti-Cancer Drug Based on Biomarker and Not Cancer Type Is Encouraging for Mesothelioma Patients

Last week MesotheliomaHelp reported on the drive towards using DNA sequencing on cancer patients in an effort to determine the appropriate treatment based on the patients’ biomarkers. Keytruda, that targets the PD-L1 marker, was cited as an example in that article. Now, the U.S. Food and Drug Administration has granted accelerated approval to Keytruda as a treatment based solely on the genetic mutations of a cancer and not on the type of cancer.

The FDA announced in a May 23 press release, that this is the first-ever approval of a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated. Keytruda has already been approved for in the U.S. for use in melanoma and lung cancer patients after a prior round of chemotherapy failed to stop progression of the disease. This approval is for unresectable or metastatic solid tumors, of any type, that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

Expert Insight

Richard Pazdur, M.D., FDA

“This is an important first for the cancer community.”

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“Until now, the FDA has approved cancer treatments based on where in the body the cancer started—for example, lung or breast cancers,” said Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.”

This approval, according to the FDA, was based on the results of five clinical trials for patients with MSI-H or dMMR solid tumors. The patients had a variety of cancers, including colorectal and endometrial. Of the 149 patients who received Keytruda in the trials, nearly 40 percent had a complete or partial response, with 78 percent of those patients seeing a lasting response for six months or longer.

“The FDA’s approval of this first-of-its-kind, tumor-agnostic, indication is further evidence of Merck’s commitment to helping people with difficult-to-treat cancers, and to advancing the use of biomarkers to guide clinical decision-making,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories, in a May 25 press release announcing the approval.

This approval has far-reaching implications for the mesothelioma community for future approvals of biomarker-driven drugs. Significant research has been conducted to find those biomarkers that drive the uncontrollable growth of mesothelioma, and other cancers, and this landmark approval moves oncologists much closer to offering personalized care. Targeted therapy improves quality of life and increases survival for cancer patients.

“This approval for Keytruda is a transformational milestone in our progress toward personalized immunotherapy, offering certain patients with difficult-to-treat cancers a medicine based on the genetic makeup of the tumor – regardless of tumor type,” said Dr. Luis A. Diaz, Jr., head of the Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center.

Mesothelioma is an asbestos-caused cancer with a prognosis often less than 18-months. New, effective treatment options are critically important to allow patients to live longer lives.

Patients should talk to their oncologists to determine whether Keytruda is a treatment option for them. Visit the Keytruda website to find out more about the drug.

 

Sources:

  • FDA
    https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm
  • Merck Research Laboratories
    http://www.mrknewsroom.com/news-release/prescription-medicine-news/fda-approves-mercks-keytruda-pembrolizumab-adult-and-pediatr
  • Keytruda website
    https://www.keytruda.com/?cc=F56EF8DC&csid=General_Brand_Lung&gclid=CjwKEAjw4IjKBRDr6p752cCUm3kSJAC-eqRtAmMqxwdRx6gjIkSciP4aQ8fZl3M5fzF-2jLSDG5kmhoCzVbw_wcB
Daughter & Father Fight Against Mesothelioma

Daughter & Father Keep Hope Alive During Fight Against Mesothelioma

Some individuals are just positive people; it’s how they are! No matter what is thrown at them or what comes their way, they have the ability to make the best of things. This, in turn, helps those around them to be optimistic, too.

My Dad was one of those people. Many individuals ask me how my family stayed so upbeat (for the most part) during our experience with mesothelioma. The simple answer was, “Dad.” When the person who has been diagnosed with this disease is the one reassuring everyone else that things will be ok, it’s hard to believe otherwise. This is not to say that I didn’t have my moments, but there was more light in my days than I expected during this time.

Some may think that I was naïve to think this way, but it was how I chose to handle it. I believe that attitude can have a direct effect on outcome, so why not think the best! Even on the days when I felt the most sadness and anxiety about Dad’s illness, he would always tell me that he would be ok. God would take care of him and all of us as well.

Going through life thinking the worst must be exhausting. Life is a challenge, bringing with it ups and downs that you may never be prepared for. But we are also meant to make the best of what we are given. Dad inspired me to always look for the best in every situation and it has truly changed my entire outlook on the world. There is inherent good in people, there is hope when all seems dark, and there is love where you couldn’t imagine it could ever be found. Never give up hope, God will always be there!

Targeted Therapy Mesothelioma Treatment

Targeted Therapy May Soon be Primary Approach for Mesothelioma Treatment

Targeted care optimizes the potential for success of mesothelioma treatment and provides the patient with the assurance that his cancer is being treated according to his unique characteristics. Personalized cancer treatment is gaining popularity among physicians and oncologists, however, it is far from mainstream. If researchers from University of Michigan have their way, however, treatment for all cancers will soon be personalized based on the patient’s biomarkers.

In a new study released from researchers at the University of Michigan Comprehensive Cancer Center, the team looked at the DNA sequencing of nearly 500 patients. Of those, almost 75 percent of them had biomarkers that can be targeted by either existing or experimental anti-cancer treatments.

Biomarkers, including EGFR and PD-L1, that are present in mesothelioma and other cancers, help indicate the reason for the growth of the cancers and are the focus of current and experimental treatments used to fight the deadly disease. Many clinical trials are being offered now for mesothelioma patients that pinpoint particular biomarkers. One well-known trial is the Keynote-28 trial, that eight-year mesothelioma survivor Mavis Nye of England participated in, that targeted the PD-L1 marker and put her mesothelioma in remission.

“Availability of biomarker trials is crucial for being able to act on these results,” says Erin Cobain, M.D., clinical lecturer of hematology/oncology at the University of Michigan Medical School.

The value of the study lies in the method used to sequence the genes and the process for developing patient care based on the results of the sequencing. Using “next generation sequencing” the team reports that the genetic sequencing looks at all of the DNA and RNA expressed within a tumor, as well as sequencing the patient’s normal genome to identify genes that may be inherited from the patient’s parents.

Expert Insight

Erin Cobain, M.D., University of Michigan

Sequencing is beginning to have a real impact on treatment recommendations.”

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Using MI-ONCOSEQ, the tool developed at the Michigan Oncology Sequencing Center, the test uses a fresh biopsy from the patient, as opposed to frozen tissue samples used by commercially-available tools, allowing the Michigan researchers to perform a more comprehensive analysis. According to the press release, commercial tests analyze only about 350 genes compared to MI-ONCOSEQ’s ability to cover at least 1,700 genes.

Mesothelioma is an incurable, asbestos-caused cancer of the membranes that surround many of the body’s vital organs, including the lungs. The cancer is highly aggressive and is resistant to many cancer treatments making it a difficult disease to treat effectively. Thus, developing a treatment protocol that specifically targets the genetic makeup of the patient’s cancer is vital for improving survival rates.

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