Category: Featured News
Can a Protein Garbage Truck Clear Out Mesothelioma Cells?
Researchers are turning to cell garbage collectors, or the proteasome, in their latest attempt to fight cancer. Scientists have known for years that proteasomes clean out unneeded or damaged proteins, now, they are focusing on lassoing them to attack cancer cells.
Two biochemists, Craig Crews and Raymond Deshaies, began discussing this possibility in 1998 in a bar. Crews, the L.B. Cullman Professor of Molecular, Cellular, and Developmental Biology at Yale University, has spent his career tinkering, as he calls it, with proteasomes. After years of research, he is on the cusp of a breakthrough treatment that can gobble up the proteins that help cause cancer.
This approach can target diseases that are considered undruggable or resistant to most treatments, like mesothelioma, a rare, terminal cancer. Currently, there is no known cure for the asbestos-caused disease that invariably recurs after building up a resistance to chemotherapy or other anti-cancer drugs that should kill the cancers. Mesothelioma is diagnosed in nearly 3,000 Americans each year.
In a 2010 presentation entitled, “Contemporary Treatment of Malignant Pleural Mesothelioma,” Nicholas J. Vogelzang, MD, Chair and Medical Director, Developmental Therapeutics Committee, US Oncology Research, Comprehensive Cancer Centers of Nevada, noted that proteasome inhibitors were one of “many new agents worthy of study” in the fight against mesothelioma. Dr. Vogelzang is a renowned medical oncologist, cancer researcher and mesothelioma expert.
Crews and Deshaies, Professor of Biology and Executive Officer for Biology Division of Biology & Biological Engineering California Institute of Technology, and founder of the Proteome Exploration Laboratory at the Beckman Institute at Caltech, have built their careers around the proteasome and have spawned several pharmaceutical companies, including Arvinas, focused on harnessing the power of the proteasome.
After rounds of research, Crews and his team found that when the proteasome was “jammed” up, toxic levels of old proteins built up in the cancer cells before the proteosome could clear them out. Without the help in throwing away the discarded proteins, the cancer cells were overwhelmed and died. Crews determined that this could be recreated by an anti-cancer drug.
“You can imagine a small molecule, a drug, that works under this new paradigm, will truly be one that can seek and destroy rogue, disease-causing proteins,” said Crews in a May 18 article in Stat News.
Crews was recently awarded the National Cancer Institute’s Outstanding Investigator Award. Crews, one of 60 U.S. scientists to receive the award, which brings $4.2 million over seven years to support his lab’s research, says the money will make a big difference in his research and could lead to “a second chance” for drugs that were abandoned because “they couldn’t block the function of rogue proteins.”
“This award will help us change the current small-molecule drug paradigm that fails to target 75% of rogue proteins,” Crews said. “Instead, we propose to hijack the cells’ quality-control machinery so that this new class of drugs can bind to and destroy these disease-causing proteins.”
If everything continues on track, Crews hopes that Arvinas, working with Merck and Genentech, will be testing this approach to cleaning up cancer within a year.
For the full story, “A tinkerer takes on cancer by hijacking the tiny garbage trucks inside every cell,” see the May 18 article in Stat News.
Key Ingredient in Aspirin Could Lead to New Treatment for Mesothelioma
The cancer-fighting properties of aspirin have long been touted. In fact, a daily aspirin may help prevent cancer, according to the American Cancer Society. Now, another study offers more evidence of a positive association between aspirin’s key ingredient, salicylic acid, and its cancer-fighting properties.
In what is encouraging news for mesothelioma patients, researchers report that both aspirin and diflunisal can stop inflammation and cancer. The two nonsteroidal anti-inflammatory drugs (NSAIDs) have the key ingredient salicylic acid that researchers from Gladstone Institutes, of San Francisco, report is effective in inhibiting two proteins, p300 and CREB-binding protein (CBP), preventing cellular damage caused by inflammation. The proteins, according to the researchers, control the levels of proteins that cause inflammation or are involved in cell growth.
“Salicylic acid is one of the oldest drugs on the planet, dating back to the Egyptians and the Greeks, but we’re still discovering new things about it,” said senior author Eric Verdin, MD, associate director of the Gladstone Institute of Virology and Immunology. “Uncovering this pathway of inflammation that salicylic acid acts upon opens up a host of new clinical possibilities for these drugs.”
For people who have previously been exposed to asbestos and face a life-long risk of developing pleural mesothelioma, a cancer of the lining of the lungs, this finding brings hope that the potential for developing the disease could be minimized. Microscopic asbestos fibers when inhaled can lodge in the lungs and remain there causing inflammation that eventually leads to pleural mesothelioma. Many of the cancer treatments are ineffective against the disease, and many experts agree, that the best way to fight the cancer is through prevention.
In the study, the researchers determined that suppressing p300 with diflunisal “stopped cancer progression and shrunk the tumors in the mouse model of leukemia.” The team has also conducted a trial in human hematologic cancers and determined the salicylic acid to be safe. The next step for them is to collaborate in the development of novel epigenetic therapies to find more effective treatment for leukemia patients.
In a separate study in 2015, researchers from the University of Hawaii Cancer Research Center “reported aspirin administration to individuals at high risk of developing MM [malignant mesothelioma], such as those with a history of asbestos …may prevent or delay the growth of MM, possibly increasing life expectancy and also increasing opportunities for early MM detection.”
“The ability to repurpose drugs that are already FDA-approved to be part of novel therapies for cancer patients is incredibly exciting,” said co-author Stephen D. Nimer, MD, director of Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine.
Although evidence may support aspirin use for its anti-cancer properties, doctors stop short of recommending aspirin to prevent cancer. Before starting an aspirin regimen please consult with your doctor.
In the United States, approximately 2,500 to 3,000 people are diagnosed with mesothelioma each year. The disease is incurable, though there are standard treatments to manage the disease including chemotherapy, radiation and surgery.
The study can be found in the May 31 issue of eLife.
Mesothelioma Patients Should Not Have to Choose Between Hospice Care and Active Treatment
One of the most important things mesothelioma patients and their families cite when it comes to end-of-life care is the desire to be home and with their family. To many in the U.S., this means hospice care and, therefore, the end of active mesothelioma cancer treatment. Now, researchers point to a model adopted by the U.S. Veteran’s Administration where hospice and active cancer care are given concurrently.
Hospice is designed to improve the quality of a patient’s last days by offering comfort and dignity, and often allows the patients to remain in their own home surrounded by their loved ones. Today, once hospice is established in the U.S. active cancer care is ended and the patient receives palliative care that is intended to control pain and relieve mesothelioma symptoms.
According to Drs. Jeanie M. Youngwerth and D. Ross Camidge from the University of Colorado, the U.S. trails behind many other countries when it comes to providing quality medical care for patients with terminal conditions. But, straying from the norm, the VA does not limit “curative” therapies while a veteran is receiving hospice care.
“Consequently, in theory, the VA would permit life-prolonging measures, such as chemotherapy, to be administered while a patient simultaneously receives hospice services,” said the doctors.
For veterans, this is good news since this population makes up one-third of those who suffer from mesothelioma, a terminal cancer caused by past asbestos exposure. Approximately 3,000 Americans are diagnosed with mesothelioma each year. Asbestos was used as insulation in military buildings and ships. It was also used as an insulator around heat and cooling systems, in Navy vessels and in the gaskets placed inside airplane engines and large machinery.
For other mesothelioma patients, the option for concurrent care is still being assessed. The doctors point out that several clinical trials found “ early initiation of palliative/hospice care with active anti cancer therapy, so called “concurrent care,” improves quality and, potentially, quantity of life for patients with advanced cancer.” In addition, they note, that a 2010 study found that “patients with advanced lung cancer did better in terms of both quality and quantity of life when they received palliative care integrated with standard anticancer care as opposed to receiving anticancer care alone.”
Other government agencies hope to join the VA in their treatment model. Centers for Medicare & Medicaid Services, through the Medicare Care Choices Model, is piloting a program for Medicare beneficiaries to receive palliative care services from certain hospice providers while concurrently receiving anticancer therapies provided by their oncology providers, according to the doctors.
Other medical professionals agree with the need for concurrent care for critically ill patients. In a 2012 presentation at the annual meeting of the American Academy of Hospice and Palliative Medicine, Dr. Diane E. Meier, director of the Center to Advance Palliative Care and professor of geriatrics and internal medicine at Mount Sinai School of Medicine, stressed that now is the time to educate physicians as well as the general public that palliative care is “actually about relieving the pain, symptoms, and stress of serious illness in patients of any age and at any stage of disease, and that palliative care can be delivered alongside curative or life-prolonging therapies.”
Sources :
- University of Colorado
https://connection.asco.org/magazine/features/hospice-and-cancer-therapy-must-we-choose-only-one
Protein Could Be Used to Develop Mesothelioma-Fighting Drug
Researchers report they have found an effective way to induce apoptosis, or cell death, and to suppress cancer growth. The team is targeting the BaK protein and has found a way to transform it “into a killer protein” that kills cancer cells. The hope is that this approach will lead to developing drugs that will be effective in fighting treatment-resistant cancers like mesothelioma.
Mesothelioma, an asbestos-caused cancer, like many cancers, is resistant to standard treatments, and, thus, to apoptosis. Apoptosis is often referred to as cell suicide because when cells are damaged they sacrifice themselves to prevent damaging additional cells. However, in cancer, the process goes amok and the diseased cells continue to divide and grow.
According to researchers from the Walter and Eliza Hall Institute of Medical Research, of Melbourne, Australia, the BaK protein, which is central to apoptosis, is present but inactive in healthy cells. But when a cell receives the trigger to die, BaK is activated and helps destroy the cell. In cancer cells that are notorious for tricking the body’s natural defense mechanisms, however, BaK is not activated and apoptosis does not occur leaving the cells unchecked.
The researchers set out to find a way to mimic the action of BaK, or to turn on the trigger to kill cancer cells. They inadvertently found an antibody they were using to simply study BaK, actually bound to the protein and triggered its activation.
“There is great interest in developing drugs that trigger Bak activation to treat diseases such as cancer where apoptosis has gone awry,” said Dr. Ruth Kluck, BSc, PhD, QLD, lead researcher and Laboratory Head of the Molecular Genetics of Cancer. “This discovery gives us a new starting point for developing therapies that directly activate Bak and cause cell death.”
In fact, the researchers are already collaborating with others to develop their antibody into a drug that can take advantage of the BaK protein.
Finding an effective way to prevent cancer cells from evading cancer death by artificially triggering it could increase the efficacy of existing treatments leading to increased survival in mesothelioma patients. Mesothelioma is diagnosed in nearly 3,000 Americans each year, and the same number die from the cancer.
The full report can be found in the May 24 issue of Nature Communications.
Mesothelioma Patients Need More Information to Help Make Treatment Decisions
When patients are faced with a life-threatening illness like mesothelioma, the more information they have the less anxious they feel about the diagnosis. Unfortunately, according to a recent study, terminally ill patients lack even basic information about their illness.
In a study conducted by a research team from Weill Cornell Medicine in New York City, led by Dr. Holly Prigerson, professor of geriatrics, researchers report that of 178 patients who were faced with highly lethal metastatic cancers, just five percent of the patients had “sufficient knowledge about their illness to make informed decisions about their care.”
“Many did not know that they were at the end-stage of their illness or that their cancer was incurable. They were basically making treatment decisions in the dark,” explained Prigerson, who also co-directs the Center for Research on End-of-Life Care at Weill Cornell.
Treatment for mesothelioma, a terminal asbestos-caused cancer, can vary from patient to patient. Primarily, treatment options consist of surgery, chemotherapy and radiation. It is critical for the patients, however, to understand their prognosis and the benefits and risks associated with each of these options to ensure they are prepared for the arduous battle ahead.
According to the researchers, doctors are reluctant to share information about terminal illnesses for fear that they will upset the patients or the patients will view the doctor less favorably. Without the information, though, many patients have a false sense of security and do not even realize they have limited survival.
The researchers concluded that patients who have discussions with their oncologists about prognosis and life expectancy “come to have a better understanding of the terminal nature of their illnesses.” They added that improvement in the area of end-of-life patient/doctor communication can improve patient-centered care.
This research points to the fact that the more knowledge patients have about their illness, the better off they are when it comes to making their own treatment decisions. In fact, previous research has pointed out that an empowered mesothelioma patient is often the best patient for a medical team. When patients are empowered it means they are informed of their disease and their treatment options, and they are willing to take an active role in their treatment.
Managing a disease such as mesothelioma can be overwhelming, but partnering with your physician from the start may be the key to receiving the best treatment. According to a 2002 article on patient empowerment in the Hong Kong Medical Journal, researchers said, “Medical knowledge has long been used in clinical practice for professionals. It is time to shift the balance of power to include patients and their caregivers.”
The study was published the May 23 edition of the Journal of Clinical Oncology.
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