Mesothelioma Help Cancer News
Metabolic Pathways, Key to Understand Mesothelioma Metastasis
The science behind understanding how mesothelioma cells continue to divide and spread despite being inundated with toxic treatments has confounded researchers for years. If cancer metastasis can be halted, patient survival will be improved. Now, researchers report they have uncovered a unique link between cancer pathways that leads to uncontrolled growth.
Researchers at Children’s Medical Center Research Institute at UT Southwestern (CRI), led by Dr. Ralph DeBerardinis, Associate Professor of CRI and Pediatrics, Director of CRI’s Genetic and Metabolic Disease Program, and Chief of the Division of Pediatric Genetics and Metabolism, found that two distinct metabolic cancer pathways are linked in such a way that cells adapt to the stress of cancer growth.
The researchers had a hunch that by focusing on “tumor-specific metabolic pathways” they could uncover a new, effective way to treat cancer. Building on previous findings by Dr. DeBarardinis, the team found cancer cells take advantage of the pentose phosphate pathway (PPP) and the Krebs cycle pathways to successfully fight off toxins.
In short, cells typically grow by “attaching to nutrient-rich tissue called a matrix,” according to the study, in order to manage growth and survival. When they detach, however, the cells perish. Not so for the cancer cells, though, say the researchers. Apparently, cancer cells have found a way to work around the process.
“We knew that both the PPP and Krebs cycle provide metabolic benefits to cancer cells,” said Dr. Ralph DeBerardinis in an April 6 press release announcing the findings. “But we had no idea that they were linked in this unusual fashion.”
According to various studies, metastasis is the cause of nearly 90 percent of cancer deaths. Halting tumor growth and preventing metastasis in cancers, especially mesothelioma which is highly aggressive and is resistant to many cancer treatments, is critical for increasing survival in patients. This research offers hope to mesothelioma and lung cancer patients that slowing or halting tumor growth is possible.
The researchers note that the study was conducted in a lab with cultured cell models. The next step is further research on living organisms.
“We are particularly excited to test whether this pathway is required for metastasis, because cancer cells need to survive in a matrix-detached state in the circulation in order to metastasize,” said Dr. DeBarardinis.
See the full report in the April 6 issue of Nature.
Know more about Mesothelioma and how you can deal with it.
In the Future, When Cancer Cells Glow Green It’s A Go For Selected Mesothelioma Treatment
Nanotechnology is in the news again with a report that a new technique can determine within eight hours whether chemotherapy is effective for a patient. For mesothelioma patients, and all cancer patients, being able to quickly assess whether a treatment is effective can mean the difference in survival.
According to a March 28 press release from Brigham and Women’s Hospital announcing the findings, a team of researchers found that they can deliver a nanoparticle of a potential cancer treatment that will fluoresce green if the cancer cells die from the drug. The results rely on the enzyme caspase that is activated when a cell dies.
“We can determine if a cancer therapy is effective within hours of treatment,” said co- author Shiladitya Sengupta, PhD, a principal investigator in BWH’s Division of Bioengineering. “Our long-term goal is to find a way to monitor outcomes very early so that we don’t give a chemotherapy drug to patients who are not responding to it.”
One test used paclitaxel chemotherapy on a prostate cancer line. The test realized “an approximately 400 percent increase in fluorescence” in the tumors that were responsive to paclitaxel compared to those cells that were paclitaxel-resistent. The technology was also successful for monitoring the effectiveness of immunotherapy. The researchers yielded “a significant increase in the fluorescent signal” in tumors sensitive to the anti-PD-L1 nanoparticles after five days.
Determining the appropriate cancer treatment for a patient is a difficult and complex decision for patients and their oncologists. Finding an effective mesothelioma treatment is even more challenging due to the relative rarity of the disease. However, the ability to detect responders, as the researchers refer to an effective treatment, and non-responders, in real-time can spare patients needless treatment and allow the oncologist to quickly adjust the treatment protocol without losing precious time.
“Current techniques, which rely on measurements of the size or metabolic state of the tumor, are sometimes unable to detect the effectiveness of an immunotherapeutic agent as the volume of the tumor may actually increase as immune cells begin to flood in to attack the tumor,” said co- author Ashish Kulkarni, an instructor in the Division of Biomedical Engineering at BWH. “Reporter nanoparticles, however, can give us an accurate read out of whether or not cancer cells are dying.”
The researchers’ next step is to assess the safety and efficacy on humans. There was no indication as to the timeline of when this research can move into a clinical setting.
Brigham and Women’s is home to the International Mesothelioma Program. Managing over 300 mesothelioma consultations per year, the International Mesothelioma Program is the largest program of its kind in the world. The Program has a mission “to offer state-of-the-art treatment to patients with malignant pleural mesothelioma.”
The full report of the BWH study can be found in The Proceedings Of The National Academy Of Sciences.
Mesothelioma Patients May Question Their Mortality
He was in the ICU from a complication after his surgery. His journey with mesothelioma had begun just three months earlier. He had presented to his local doctor with what he thought was pneumonia- it wasn’t. Previously healthy, he was diagnosed with epithelioid mesothelioma. He and his family had researched mesothelioma, came to an academic center, had surgery. Things had been going well and then he had an unexpected complication – treatable – but unexpected.
Physically he was recovering, mentally he was devastated. He knew about the possibilities of complications since they had been explained in depth to him and he had accepted the risks of the surgery. Before the complication he was beginning to see that he and his family could cope with and live with mesothelioma. He was beginning to feel that he had regained control of his life. Now, he lies in the bed wanting to know if death was imminent.
The psychological toll that the complication had taken on him was worse than the physical setback.
As the nurse, I know that he will get better from the complication physically, I can point out all the evidence that it will happen, he is ex-tubated, his vital signs are good, he is not on oxygen, he will soon be transferred to the step down unit. All positive signs that he is on the mend.
What about his mental state? He had done everything that was asked of him after surgery, and had landed back in the I.C.U- what does that say about his prognosis? Once diagnosed with cancer, and when having treatment, finishing treatment, whether it be surgery, chemo, radiation, or clinical trial, in the back of every patient’s mind is the question, “When will I have a recurrence?” Every patient needs to process and deal with this possibility.
The way to help is to listen and support the patient. Know that everyone responds to complications differently. Point out the positives in the patient’s situation, for example, physically you are better. Acknowledge that it takes time to adjust to a diagnosis of cancer, and that there are ramifications. A cheery pep talk might not be appropriate, but simply pointing to the facts might help. Like every mesothelioma tumor is different, every patient’s reaction is different. It is important to accept that and adjust your approach.
I am happy to report that the mesothelioma patient in ICU did get physically and mentally better. He is adjusting – time, family love, and support can be the best medicine!
Existing Anti-Cancer Drug May be Effective in Lung Cancer and Mesothelioma Patients
Before oncologists can tackle a patient’s cancer they need to know the type of cancer, of course, but knowing what biomarkers comprise the cancer can lead to treatment with a targeted therapy. Targeted therapy is especially critical for aggressive cancers like mesothelioma and lung cancer. Now, researchers report they have found a genetic marker to help identify lung cancer patients who will benefit from an existing anti-cancer drug, imatinib.
Researchers from the Cancer Research UK, Manchester Institute report the Abelson (ABL) family of nonreceptor tyrosine kinases, ABL1 and ABL2, are “mutated or amplified” in nearly 10% of lung cancer cases. The markers, according to the researchers, are key to tumor growth and could give oncologists another way to identify and treat lung cancer patients.
“Drugs that block the activity of the ABL proteins have been used to successfully treat leukaemia patients, where ABL is overactive,” said Dr John Brognard, who led the study, in the March 22 press release announcing the findings. “However, until now, the role of ABL1 and ABL2 in other cancer types hasn’t really been explored.”
The researchers found that ABL1 mutations helped lung cancer cells thrive. However, when the ABL inhibitor, imatinib, approved by the U.S. Food and Drug Administration for leukemia and certain GI tumors, was applied in the lab, it effectively blocked tumor growth.
A 2008 study by researchers in Italy found that imatinib “enhances the therapeutic response to gemcitabine” in combination treatment for malignant mesothelioma.
Pleural mesothelioma, an asbestos-caused cancer of the lining of the lungs, is often treated with similar protocols as lung cancer. Both cancers have shown to be aggressive and often reject and defeat many of the common treatments. However, care that focuses on a patient’s unique traits, such as specific biomarkers like ABL1, allows the oncologists to personalize treatment.
Medical care targeted to a patient’s unique characteristics and genetic makeup optimizes the potential for success of the treatment and offers treatment options that may not otherwise have been considered.
“Drugs like imatinib are already commercially available,” says Dr. Brognard. “This means that we now have an extra ready-made tool for the treatment of lung cancer – we just need to identify which patients will benefit by doing some additional tests.”
“Holy Grail of Medicine” Could Bring a New Way To Treat Mesothelioma
Cancer researchers have been focusing much of their attention on using nanotechnology to deliver cancer-fighting drugs directly to cancerous cells, thus, leaving healthy cells intact. Australian researchers have developed an approach much like the Trojan Horse delivery method Mesothelioma Help reported on last month, but the researchers are touting their method of deploying nanotechnology to kill cancer cells as the “holy grail of medicine.”
Researchers at Flinders University in South Australia are making this claim, and adding that this will revolutionize the way cancer is treated, due to the “smart packages” ability to attack and destroy cancer cells “more efficiently and reduce side effects.” The unique packages contain folate molecules that are attracted to cancer cells that have a lower pH level than healthy cells.
“The way we have designed the vehicle is that you can use it for any number of different cancer cells or combination of different cancer cells,” said Professor Colin Raston, co-lead of the research, according to a March 24 The Lead South Australia article. “You can load it up and target them using specific types of drugs, which we know are for those particular cancers.”
The researchers developed the anti-cancer delivery mechanism that is just 100 nanometres in diameter, or nearly 800 times finer than a human hair, according to the report. Inside the package is a dose of chemotherapy, that, when it finds the cancer cell with low pH levels, “it becomes unstable and delivers the anti-cancer drug inside,” Professor Raston said.
Raston adds that because of the unique way the package binds to the cancer cells, less of the drug is needed “shutting down all the side effects.”
Side effects from the often toxic doses of chemotherapy required to kill cancer cells are well-known and can be debilitating to many patients. For mesothelioma patients who are already in a weakened state, finding a way to bypass the nausea, low blood count, and fatigue can make a difference in the patients’ attitude and survival.
Mesothelioma is a serious cancer that occurs in individuals exposed to airborne asbestos fibers. Although there is no cure for mesothelioma, it can be treated with varying degrees of success through the use of surgical procedures, chemotherapy and radiation.
The research was conducted in a lab on lung cancer treated via a paclitaxel-laden smart package. Paclitaxel is used by some oncologists, typically in combination with another anti-cancer drug, for lung cancer and mesothelioma.
The researchers concluded, this approach “can significantly enhance the utility of nanoparticle delivery technology to tumours.” They added that animal experiments will need to be conducted to assess the “feasibility and safety” of the approach.
The study was published in the March 24 issue of Scientific Reports.
http://www.nature.com/articles/srep23489
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