Roche launches Elecsys Anti-p53 immunoassay to aid diagnosis of various cancer types

Source: www.globenewswire.com
Author: press release, F. Hoffmann-La Roche Ltd

Roche today announced the launch of the Elecsys Anti-p53 immunoassay for the in vitro quantitative determination of anti-p53 antibodies. This test is used to aid physicians to diagnose throat cancer, bowel cancer and breast cancer in patients, in conjunction with other diagnostic tests. The assay is now available for all markets accepting the CE Mark.

“The addition of our Elecsys Anti-p53 immunoassay will help clinicians to quickly and reliably diagnose several prevalent cancers and might assist in leading to a better prognosis for many patients.”, said Thomas Schinecker, CEO Roche Diagnostics. “Beyond breakthrough cancer medicines, Roche also offers a growing number of testing solutions to help physicians diagnose and treat people with cancer.

p53 is protein which, when active, helps to regulate processes which stop tumors from developing. A mutation of p53 is present in half of solid tumor cancers and is the most common genetic change identified so far in human cancers.1 Certain mutations of p53 can lead to a build up of p53 which results in the formation of anti-p53 autoantibodies. Autoantibodies are antibodies that mistakenly target and react with a person’s own tissues. Between 20-50% of patients with mutated p53 will produce anti-p53 autoantibodies.2 This mutation causes the tumor suppressive function of p53 to switch to a tumor-promoting function and thus cancer development.

Early appearance of anti-p53 antibodies during tumour development may have potential to detect malignant changes.3 The Elecsys Anti-p53 immunoassay detects these anti-p53 antibodies and, when used with other diagnostic tests, can help to diagnose certain cancers, at an earlier stage, which may help to improve patient outcomes. Determining the presence of anti-p53 antibodies may also be useful for monitoring cancerous cells that are still in the body following treatment.4 In addition, the Elecsys Anti-p53 test could aid in determining which patients may require less invasive treatment procedures, as part of their cancer treatment.

About Elecsys Anti-p53
Elecsys Anti-p53 immunoassay for the in vitro quantitative determination of anti-p53 autoantibodies in human serum and plasma. Elecsys Anti-p53 is a high precision immunoassay, with a low turn-around time for testing, complementing our overall tumor marker portfolio. The new Elecsys Anti-p53 immunoassay uses the well-established electrochemiluminescence immunoassay “ECLIA” technology and is intended for use on cobas e immunoassay analyzers.

For further information on Elecsys immunoassays visit here.

References
[1] Yue X, et al. J Mol Biol 2017;429:1595-606
[2] Suppiach et al. World J Gastroenterol 2013 August 7; 19(29): 4651-4670
[3] Soussi T. Cancer Res 2000;60:1777-88
[4] Kastenhuber E & Lowe S. Cell 2017;170(6):1062-78

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Your cancer answers: can nutrition, exercise improve quality of life for head, neck cancer patients?

Source: syvnews.com
Author: John Malinowski, Marian Cancer Care

Question: How can nutrition and exercise improve quality of life for head and neck cancer patients?

Head and neck cancers affect more than 52,000 Americans each year and account for about 5% of new cancer cases worldwide. Treatment of head and neck cancer with concurrent chemo radiotherapy with curative intent may cause side effects leading to deterioration of long-term quality of life and disability that persists years after treatment.

Many head and neck cancer patients experience treatment related side effects such as; difficulty swallowing, difficulty with speech, loss of taste or smell and unintended weight loss which often can be attributed to decreased muscle mass.

There are a few things that you can do to try helping to maintain your body weight during treatment. Nutrition can be one tool to help ensure you are taking in enough calories and the right nutrients to help your body fight the cancer.

Often when undergoing cancer treatments our body has an increased demand of caloric intake. This can be a challenge to increase your calories while undergoing treatment so try eating several smaller meals throughout the day, maybe even every 2-3 hours. With each meal try to incorporate some carbohydrates, fats, and protein.

Make sure you are intentional about chewing your food. You can try to chew each bite 50 times or trying to incorporate softer texture foods can make it easier to swallow. Steaming or boiling vegetables rather than eating raw may help. Softer foods like scrambled eggs, egg salad, soups or stews, oatmeal or cream of wheat, tofu, milk, yogurt, cottage cheese, casseroles, mashed potatoes or macaroni and cheese are just a few options.

Knowing that your body requires an increase in protein intake during treatment think about having snacks with protein close by. Having Greek yogurt or pre-made smoothies like Ensure or Reason can be a quick high protein snack.

It is becoming widely known that exercising while going through treatment can help reduce symptoms like fatigue, nausea and anxiety or depression however a more important side effect a head or neck cancer patient may need to think about is the loss of body weight or muscle mass.

Incorporating an exercise routine which involves resistance exercises at a moderate intensity for your major muscle groups can help you maintain the muscle mass you have which can help you continue to perform the daily activities you want and need to do. It is also important to work smaller muscles of the neck to maintain function of swallowing and speech. A few exercises to try are:

Effortful Swallow – Collect saliva on your tongue then press your tongue hard against the roof of your mouth and swallow deliberately. Do three sets of 25 aiming for one swallow every 10 seconds.

Straw against resistance – Place a straw between your lips as if you were going to take a sip of liquid. Place a finger partially over the opening on the bottom of the straw and suck in. Feel your lips wrap around the straw tight! Do three sets of 10 repetitions.

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HPV vaccine leads to more than 80% drop in infections: What parents need to know

Source: Good Morning, America
Date: April 2nd, 2021
Author: Kathleen Kindalen

 

A new study has shown the effectiveness of the HPV vaccine, and found a dramatic decline in human papillomavirus infections in both vaccinated and unvaccinated teen girls and young women in the United States.

“This study shows that the vaccine works very well against a common virus, HPV,” Dr. Hannah Rosenblum, lead author of the study and medical epidemiologist at the Centers for Disease Control and Prevention (CDC), told “Good Morning America.”

“HPV can cause serious health problems later in life, including some cancers in both women and men,” she said. “HPV vaccination is cancer prevention — by vaccinating children at age 11 or 12, we can protect them from developing cancers later in life.”

HPV is the most common sexually transmitted infection in the United States and can cause health problems like genital warts in addition to cancer, which are most commonly cervical cancer in women and throat cancer in men, according to the CDC.

The HPV vaccine was first authorized in the U.S. for females in 2006, and for males in 2011. There has since been a more than 80% decline in HPV infections nationally, according to the CDC study.

The newly-released data from the CDC shows an 88% decrease in HPV infections among 14 to 19-year-old females and an 81% decrease among 20 to 24-year-old females.

There has also been a drop in unvaccinated females, according to Rosenblum, who warned that does not mean people should let their guard down.

“We also see an effect among unvaccinated females in these age groups due to less spread of the virus, however, unvaccinated persons are not immune and are still at risk of getting HPV,” she said. “They should talk to their doctor about getting vaccinated if they are 26-years-old or younger.”

HPV viruses are found in 80 million people in the United States, according to the CDC. There are hundreds of subtypes of HPV, and 1 in 4 people in the U.S. are infected with HPV at some point in their lives.

The CDC recommends two doses of the HPV vaccine, taken six to 12 months apart, for all girls and boys ages 11 to 12, but says the vaccine can be given to children as young as 9.

Teens and older who are not vaccinated are encouraged to do so by the age of 26. People ages 15 and older need three doses of the vaccine, according to the CDC.

The timing of the vaccine has to do with the state of children’s immune systems and also trying to vaccinate pre-teens before they are sexually active, Dr. Laura Riley, chair of obstetrics and gynecology at Weill Cornell Medicine and New York-Presbyterian in New York City, told “GMA.”

“Your immune system [at ages 11 and 12] is such that you have a robust response to this vaccine, and it lasts for a really long time,” she said. “But if you haven’t had it, still continue talking to your doctor about getting it up to age 26.”

Riley said she hopes the CDC’s new data — which stands out for being a 10-year study — combined with the safety of the HPV vaccine eases any remaining concerns parents may have about getting their children vaccinated against HPV.

“When [the HPV vaccine] first rolled out, the message wasn’t quite clear, so instead of people recognizing that you were going to prevent your kid from getting cancer, people were focused on the fact that HPV is a sexually transmitted disease,” she said. “The education has to continue so that parents can understand the real benefit of this vaccine.”

“The real benefit is to prevent your child from getting cervical cancer,” Riley said. “The fact that you can prevent [cervical cancer] with a vaccine that has been used for years and has shown to be safe, why wouldn’t you do it?”

Long-lasting infection with certain types of HPV is the main cause of cervical cancer, which has the best survival rates if detected early according to the CDC. Doctors routinely screen for cervical cancer with the Pap test and HPV DNA testing depending on age and risk factors.

“We need to make sure that the teenagers and pre-teens are getting the benefit of the HPV vaccine, because it really is an anti-cancer vaccine,” said Riley. “[Cervical cancer] is a really devastating disease.”

Globally, a woman loses her life to cervical cancer every two minutes, according to a 2019 article published in the medical journal The Lancet.

In the U.S., doctors on the frontlines like Riley said more must continue to be done to educate parents about the HPV vaccine and make sure that all children across the country have access to the vaccine. As of 2018, nearly 40% of adults ages 18 to 26 reported receiving one or more doses of the HPV vaccine, according to the CDC.

“We need to make sure that we work on access to this vaccine and make sure that all girls of all races and ethnicities have the access,” said Riley. “And we need to be sure that the message is clear so that everyone gets the two doses of the vaccine, because that’s what is associated with the best protection.”

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City offers Oral Cancer Screenings; Health Officials aim to reduce cancer rates, save lives

Source: El Paso Herald Post
Date: April 1st, 2021
Author: Staff Reporter

Thursday morning, city officials announced that they will be offering referral services and health screenings to decrease the rate of oral cancer diagnoses and save lives, in recognition of April’s National Oral Cancer Awareness Month.

“Improving oral and oropharyngeal cancer awareness in our community is imperative,” said Angela Mora, Department of Public Health Director.

“Oral cancer has an incidence rate of about 7.2 per 100,000 residents in El Paso County and affects males twice as much as females in the U.S., but we as a community can work to reduce the incidence rate by participating in Oral Cancer Awareness month.”

Mora said residents can take part in Oral Cancer Awareness month by:

  • Reducing the use of tobacco products

Tobacco use and vaping significantly increases the risk of infection by the human papillomavirus (HPV) which causes oral or oropharyngeal cancer.

  • Getting Screened

Oral and oropharyngeal cancers occur most often in the tongue, soft and hard palate, tonsils, gums and back of the throat which is why regular oral and dental examinations by a health professional is important.

  • Getting the Human Papilloma Virus (HPV) Vaccine

According to the CDC, HPV is known to cause approximately 70 percent of oral and oropharyngeal cancer cases, and the HPV vaccine was developed to prevent infection by the high-risk types of HPV that cause cancers such as oral and oropharyngeal cancer.

For more information on the services and health screenings provided by the Department of Public Health visit EPHealth.com under the Services Tab Education and Promotion or call 2-1-1.

 

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UB awarded $1.5 million to reprogram white blood cells in fight against oral cancer

Source: Science Magazine
Date: March 25th, 2021

BUFFALO, N.Y. – The University at Buffalo has received a $1.5 million grant from the United States Department of Defense to develop new therapies that help reduce chronic inflammation and immunosuppression in oral cancers.

Through the three-year grant, the research will center on a type of white blood cell called a macrophage that – after migrating to oral tumors – triggers uncontrolled inflammation, which suppresses the body’s immune response and lowers the effectiveness of anticancer therapies.

The researchers aim to reprogram the macrophages by targeting genes that regulate inflammation. By lowering inflammation, oral cancers will become more sensitive to new and traditional chemotherapies.

If successful, the findings could help increase survivorship of oral cancers, which claim the life of roughly half of all oral cancer patients within five years, according to Keith Kirkwood, DDS, PhD, principal investigator, Centennial Endowed Chair and professor of oral biology in the UB School of Dental Medicine.

“A change in behavior in the white blood cells within the tumor itself removes the ‘brakes’ in the system, causing more oral cancer growth,” says Kirkwood, also associate dean for innovation and technology transfer in the UB School of Dental Medicine. “We propose to reprogram the white blood cells to regain control of the brakes.”

Additional investigators from Roswell Park Comprehensive Cancer Center include Wesley Hicks Jr., MD, DDS, chair of the Department of Head and Neck/Plastic and Reconstructive Surgery; William Magner, PhD, scientist in the Department of Immunology; and Scott Abrams, PhD, professor in the Department of Immunology.

The research will focus on oral squamous cell carcinoma, the most common type of oral cancer. Found in the lips, mouth or throat, oral cancers can affect the ability to eat and speak, and may cause permanent disfigurement of the face.

Veterans are two times more likely to develop head and neck cancers than non-veterans, says Kirkwood. The increased risk may be attributed to higher rates of alcohol and tobacco use among veterans, he says. Nearly 75% of oral cancers are caused by either alcohol or tobacco use, according to outside research.

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Deactivating cancer cell gene boosts immunotherapy for head and neck cancers

Source: newsroom.ucla.edu
Author: Brianna Aldrich

By targeting an enzyme that plays a key role in head and neck cancer cells, researchers from the UCLA School of Dentistry were able to significantly slow the growth and spread of tumors in mice and enhance the effectiveness of an immunotherapy to which these types of cancers often become resistant.

Their findings, published online in the journal Molecular Cell, could help researchers develop more refined approaches to combating highly invasive head and neck squamous cell cancers, which primarily affect the mouth, nose and throat.

Immunotherapy, which is used as a clinical treatment for various cancers, harnesses the body’s natural defenses to combat disease. Yet some cancers, including head and neck squamous cell carcinomas, don’t respond as well to the therapy as others do. The prognosis for these head and neck cancers is poor, with a high five-year mortality rate, and there is an urgent need for effective treatments.

The UCLA research team, led by distinguished professor Dr. Cun-Yu Wang, chair of oral biology at the dentistry school, demonstrated that by targeting a vulnerability in the cellular process of tumor duplication and immunity, they could affect tumor cells’ response to immunotherapy.

The enzyme they focused on, KDM4A, is what is known as an epigenetic factor — a molecule that regulates gene expression, silencing some genes in cells and activating others. In squamous cell head and neck cancers, overexpression of KDM4A promotes gene expression associated with cancer cell replication and spread.

It is well known that tumor cells can spread undetected by the immune system and, without surveillance, can metastasize to lymph nodes or other parts of the body. In this instance, tumor cells that develop in the epithelial layer that lines the structures of the head and neck can turn into head and neck squamous cell carcinoma when unchecked.

Cancer cell replication occurs through the abnormal spread and activation of signaling pathways for cancer cells, and the researchers asked the question: If we can disrupt these processes and identify a vulnerability, can we change the body’s response to fighting cancer cells and its response to outside immunotherapy?

“We know that the KDM4A gene plays a critical role in cancer cell replication and spread, so we focused our study on removing this gene to see if we would get an opposite response,” said Wang, the study’s corresponding author and a member of the UCLA Jonsson Comprehensive Cancer Center.

By removing the KDM4A gene in their mouse models, the researchers witnessed a notable decrease in squamous cell carcinomas and far less metastasis of cancer to the lymph nodes — a precursor to the spread of the disease throughout the body. Surprisingly, they also discovered that the KDM4A’s removal also led to the recruitment and activation of the body’s infection-fighting T cells, which killed cancer cells and stimulated inherent tumor immunity.

They then sought to uncover why the squamous carcinoma cells had such a poor response to immunotherapy treatment. In another set of mouse models, they again removed KDM4A and introduced a PD-1 blockade, which signals immunotherapy drugs to attack cancer cells. The combination of immunotherapy and KDM4A removal further decreased squamous cell cancer growth and lymph node metastasis.

Next, the researchers tested whether a small-molecule inhibitor of KDM4A could improve the efficacy of the original PD-1 blockade–based immunotherapy. They found that the inhibitor also significantly helped remove cancer stem cells, which are associated with cancer relapse.

The findings hold promise for the development of more specific inhibitors for KDM4A and more effective cancer immunotherapies.

“I am continuously impressed by Dr. Cun-Yu Wang and his team for breaking through barriers in our understanding of cancer-causing cellular processes,” said Dr. Paul Krebsbach, dean and professor at the UCLA School of Dentistry. “The results of this study have major implications for the development of more effective, life-saving cancer therapies.”

The work was supported by grants from the National Institute of Dental and Craniofacial Research, which is part of the National Institutes of Health.

Dr. Wang is the Dr. No-Hee Park Professor of Dentistry at UCLA, a professor at the UCLA Samueli School of Engineering and a member of Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Additional authors include Wuchang Zhang, Wei Liu, Lingfei Jia, Demeng Chen and Dr. Insoon Chang, all of the Laboratory of Molecular Signaling at the UCLA School of Dentistry and members of the Jonsson Comprehensive Cancer Center, and Dr. Michael Lake and Laurent Bentolila, both of the California NanoSystems Institute at UCLA.

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Deal-making in head and neck cancer to start yielding dividends for patients

Source: www.thepharmaletter.com
Author: staff

A frenzy of deal-making activity in head and neck cancer is bringing late-stage clinical candidates into view, according to GlobalData.

Intelligence from the data and analytics provider shows that there have been some 340 licensing agreements since 2004 in head and neck cancer, amounting to an approximate total value of $35 billion.

Aarohi Rede, oncology analyst at GlobalData, said: “The past few years have seen several licensing deals globally for clinical development in head and neck cancer. Merck KGaA’s collaboration with Debiopharm has the potential to transform the current treatment paradigm for head and neck squamous cell carcinoma (HNSCC) by combining xevinapant, a new molecular entity, with Merck KGaA’s strong commercialization capabilities.”

Of the total licensing agreements signed, the highest recorded licensing agreements took place in North America, followed by Asia-Pacific, while the lowest recorded number of deals belonged to South and Central America.

Dr Rede added: “Head and neck cancer is largely a chemotherapy-dominated market, but the past few years have seen effective use of Keytruda (pembrolizumab) and Bristol Myers Squibb’s Opdivo (nivolumab) in the recurrent or metastatic settings. The current clinical development pipeline has around 20 late-stage agents in the immuno-modulating therapy or cell inhibitor classes, thus revealing a robust late-stage pipeline that is highly conducive to future partnerships for licensing and commercialization, and is expected to contribute to significant market growth over the next ten years.”

Many of these licensing deals involve strategic partnerships between Asia-Pacific, namely Chinese manufacturers, and US pharmaceuticals for joint clinical and commercial development of oncology assets, with the purpose of gaining market access in the USA.

“While the currently marketed agents are patent protected, the introduction of drugs through these alliances poses competition for some of the premium-priced therapies, both from a market share and price perspective,” Dr Rede said.

“While licensing agreements have been one of the key business development tactics in oncology, venture financing ($8.6 billion valuation), asset transactions ($4 billion valuation), and contract service agreements ($30 million valuation) are some of the other investment approaches considered in recent years to advance drug development science in the head and neck space by way of investment capitalism.”

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On treating advanced head and neck cancer without cisplatin – an oncology grand rounds discussion

Source: www.medpagetoday.com
Author: Mark L. Fuerst

An oncology grand rounds discussion with Sachin Jhawar, MD.

Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous set of diseases with different features and treatment recommendations. Physicians face challenges in initial treatment decision-making and response assessments, including the changing role of surgery, the incorporation of human papilloma and Epstein Barr virus status, as well as the potential for treatment de-escalation using patient-related and tumor-related factors.

A recent “Oncology Grand Rounds” article in the Journal of Clinical Oncology provides an overview of treating advanced HNSCC when cisplatin is not an option, including concurrent chemotherapy, cetuximab, targeted therapy, and immunotherapy.

In the following interview, the paper’s lead author, Sachin Jhawar, MD, of Ohio State University Comprehensive Cancer Center in Columbus, reviews the main issues.

What is the focus of the article?
Jhawar:
We focused on patients with locally advanced disease who would be receiving definitive non-surgical treatment when possible treatment with concurrent cisplatin, delivered either every 3 weeks or weekly, is always the preferred treatment.

We specifically wanted to delve into the subset of patients who we would not recommend to receive cisplatin because of age or comorbidities. This could be concurrent chemotherapy (carboplatin/paclitaxel), concurrent cetuximab, and altered or standard fractionation radiation schedules without systemic therapy, as well as when to consider immunotherapy and palliative radiation for those with recurrent or metastatic disease.

There is also a great deal of institutional preference involved. At our institution, we prefer concurrent carboplatin/paclitaxel in patients who cannot receive cisplatin. Generally, we reserve definitive radiation alone options for patients who are completely ineligible for any systemic therapy.

If definitive therapy would be considered too difficult, or for those who have metastatic disease, still other palliative regimens are available.

When should clinicians consider nivolumab or pembrolizumab?
Jhawar:
At this time, immuno-oncology agents such as nivolumab or pembrolizumab are approved and used regularly only in the recurrent or metastatic setting. Even in the recurrent setting, they are generally considered only if surgery or re-irradiation therapy is not an option.

These novel agents should only be considered earlier in a patient’s treatment course in place of more traditional systemic options via a clinical trial.

What are the potential benefits of the combined use of immunotherapy, chemotherapy, and vaccines?
Jhawar:
The potential benefits of combination strategies using checkpoint inhibitors and other immuno-oncology treatments, including vaccines, in combination with more traditional therapies including surgery, radiation, and chemotherapy are still being worked out. It is likely that we will first see applications of these newer therapies in the recurrent and metastatic setting, but they may be incorporated earlier into patient care as more data about safety and efficacy emerges.

We have seen regular use of immuno-oncology treatments in other disease sites, and these therapies are being introduced earlier in the treatment course for patients. I would expect a similar pattern to emerge for HNSCC, although we will need to wait for phase III randomized controlled trial data for these immunotherapies to be ready for prime time.

It should be noted, however, that given the heterogeneity of HNSCC, there are certain scenarios in which we are working towards de-escalation of therapy, and addition of more therapies may not be needed.

In the patients with HPV-positive oropharyngeal squamous cell carcinoma and less than 10 pack-year smoking histories, the cure rates are more than 90% with current standard-of-care treatment. We are now working towards de-escalating therapy. It is not clear what role, if any, immuno-oncology will play in these already favorable situations.

What about the potential synergy of molecular targeted agents with radiation?
Jhawar:
There are multiple potential targets that could lead to synergy with radiation. Cetuximab actually acts on one of these targets, the epidermal growth factor receptor. Other potential targets that are being studied for combinations with radiation include cell signaling pathways (mTOR, AKT), cancer metabolism, tumor hypoxia, and DNA repair pathways (PARP, ATR).

There are other studies that have been completed or are ongoing that use agents to improve radioprotection of normal tissues. To date, none of these targeted agents are being regularly used on their own or in combination in the care of patients outside of clinical trials.

What improvements with new targeted therapies and immunotherapies do you foresee?
Jhawar:
As our understanding of the molecular mechanisms of carcinogenesis, aberrant cancer signaling pathways, and the tumor microenvironment improves, I expect that the number of targets and, therefore, the number of molecular targeted agents will grow. This will lead to a large increase in the number of clinical trials and expansion of our armamentarium against HNSCC.

Similarly, as our understanding of the interplay between cancer and the immune system and mechanism of immune escape improves, I suspect we will be able to improve response rates from immuno-oncology drugs. Currently, only 10% to 20% of patients respond to immuno-oncology treatments, leaving a great deal of room for improvement.

Taken together, this will allow for more individualized, patient-specific care and afford the ability to test novel combinations to improve cure rates. Simultaneously, this will decrease toxicity by choosing the right treatment for the right patient, rather than having a one-size-fits-all approach to therapy.

What’s the take-home message for practicing oncologists?
Jhawar:
There is a great deal of change forthcoming in the treatment of HNSCC, but at this time standard-of-care therapy still consists of some combination of traditional cancer therapies, including radiation, surgery, and chemotherapy.

Read the study here and expert commentary about the clinical implications here.

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A new type of recyclable: Finding new uses for established drugs

Source: www.eurekalert.org
Author: news release

Researchers from Tokyo Medical and Dental University (TMDU) uncover potential novel therapeutic strategies for oral and esophageal carcinomas

Discovering and treating tumors before they spread throughout the body is key for cancer patients to achieve positive outcomes. When tumor cells spread, which is known as metastasis, they can take over other organs and lead to death. Oral and esophageal carcinomas, or mouth and throat cancers, frequently metastasize to the lymph nodes. Unfortunately, there are currently no therapies that are specific to treating these particular cancers. Now, researchers at Tokyo Medical and Dental University (TMDU) identified several drugs that can possibly be used to treat oral and esophageal carcinomas.

In an article published in Molecular Cancer Research, a group of researchers from TMDU found that combining two drugs, pitavastatin and capmatinib, inhibited the viability of oral cancer cells in culture, as well as the growth of tumors in a mouse model.

Although esophageal carcinoma is the sixth most deadly cancer worldwide and is relatively well understood at the molecular level, the research has not been translated into specific therapeutic development. Because of this urgent need, the TMDU group became interested in drug repurposing, where a drug that has been approved for a certain disease can be used to effectively treat an additional indication. This concept significantly speeds up the drug discovery and development process, increasing the number of patients that can benefit from an established therapeutic.

“Drug repurposing can be extremely helpful for discovering efficacious treatments for diseases lacking approved therapies,” says lead author of the study Tomoki Muramatsu “We began this process for oral and esophageal carcinomas by screening an FDA-approved drug library.”

The researchers performed the drug screening on a highly metastatic oral cancer cell line. Overall, the drug pitavastatin reduced the growth of these cells most significantly. Through molecular analysis, they determined that pitavastatin acted by inhibiting a cellular pathway called MET signaling. Because of this, the researchers added in a second MET inhibitor drug, known as capmatinib.

“Combining pitavastatin with capmatinib resulted in an even greater reduction in cancer cell growth,” describes senior author Johji Inazawa. “Capmatinib by itself had no effect on the cancer cells, but it synergized with pitavastatin.”

The researchers then injected these cells into mice to generate tumors and observed a similar effect with the pitavastatin and capmatinib combination.

“Our results in the mouse model corroborated our in vitro findings,” says Muramatsu. “The data suggest that MET signaling may be a valuable therapeutic target in these tumors.”

The study also identified a potential biomarker for these particular cancers – a gene called GGPS1. Expression levels of this gene may correlate with patient responsiveness to pitavastatin. This work provides knowledge that may be vital for identifying therapeutics for these devastating diseases.

Note:
The article, “Suppression of MET signaling mediated by pitavastatin and capmatinib inhibits oral and esophageal cancer cell growth,” was published in Molecular Cancer Research at DOI: 10.1158/1541-7786.MCR-20-0688.

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First UK clinical trial in proton beam therapy

Source: www.icr.ac.uk
Author: staff

Image: The Proton Beam Scanner. Credit: The Royal Christie NHS Foundation Trust

The first proton beam therapy clinical trial in the UK, co-led by The Institute of Cancer Research, London, is now taking place at The Christie NHS Foundation Trust in Manchester. The trial will determine whether the use of proton beam therapy reduces long-term side effects and improves quality of life for patients treated with radiotherapy for throat cancer.

The study, funded by Cancer Research UK with support from The Taylor Family Foundation started last year and, despite the Covid-19 pandemic, is recruiting ahead of target, with 37 patients so far taking part. In total 183 people will take part in the study, about two thirds will receive proton beam therapy, and a third will receive standard radiotherapy.

State of the art proton beam therapy
Currently all patients allocated proton treatment within the trial, which is called TORPEdO, receive this at the state of the art NHS proton beam therapy centre at The Christie in Manchester, which opened in 2018. Another centre is currently being built at University College London Hospitals.

A combination of chemotherapy and radiotherapy is usually effective in curing head and neck cancers, but radiotherapy can damage the healthy surrounding tissue. This can result in severe long-term side effects including dry mouth, loss of taste, difficulty chewing and swallowing and problems with hearing. Some patients might need to use a feeding tube for the rest of their lives.

Precisely target tumours
Proton beam therapy uses charged particles instead of X-rays and can target tumours more precisely, causing less damage to surrounding tissues.

A year after treatment, patients will be asked about their quality of life and doctors will assess the impact of any side-effects, and whether they still need to use a feeding tube a year after treatment, or have lost a significant amount of weight.

First proton beam therapy trial in the UK
Dr David Thomson, consultant clinical oncologist at The Christie and chief investigator on the trial, said:

“It’s very exciting and a privilege to conduct the first proton beam therapy trial in the UK here in Manchester. In what is a true team effort, the amount of support from colleagues across the country has been fantastic. There’s a real need to develop treatments which cause less side effects and improve long-term quality of life for patients with head and neck cancer. Proton beam therapy may do this, by reducing the damage to healthy surrounding tissues, so it was an obvious patient group to research first.

“Currently the proton beam therapy unit at The Christie is mainly used for children and young adults. We would like to make the facility available for other groups of adult patients who may benefit most from it too. The first step is to determine whether proton beam therapy improves side effects and quality of life for patients with throat cancer.”

Potentially transformative for patients
Professor Emma Hall, Deputy Director of the Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, who co-leads the study, said:

“Radiotherapy is a highly effective treatment involved in around 40 per cent of cancer cures, but it can cause side effects where radiation affects nearby tissues, and this can be a particular problem for patients with throat cancers. Proton beam therapy has the potential to target tumours more precisely, with less spillover of radiation into the neighbouring healthy tissue.

“We think that for patients with throat cancer, proton beam therapy could be transformative – minimising side effects, improving recovery and sparing some people the long-term impacts of treatment, such as the need to use a feeding tube. This trial is an important first step in understanding if proton beam therapy can deliver on its promise, and if so who stands to benefit most.”

The researchers will also study which patients benefit most from proton beam therapy to help them determine who to offer the treatment to in the future in terms of who is most likely to see long-term improvements.

Around 11,700 people are diagnosed with head and neck cancer every year in the UK, and more than 8 in 10 patients suffering from throat cancer – such as tonsil and base of tongue cancer – receive radiotherapy as part of their treatment.

‘An incredible achievement’
Michelle Mitchell, chief executive of Cancer Research UK, said:

“It’s fantastic to hear that despite the challenges that this pandemic has thrown at us, patients with head and neck cancer have been able to access cutting-edge treatments like proton beam therapy. Many patients used to have to travel abroad to receive this type of treatment, so to be pioneering its use for adults in the UK is an incredible achievement.

“Cancer Research UK has a solid history of delivering practice-changing radiotherapy trials, which included making IMRT the gold standard for treating head and neck cancers. But there is always room for improvement, and we hope that proton beam therapy will be the next step in transforming the lives of people with neck and head cancer.”

Neville Shepherd from The Taylor Family Foundation said:

“We are delighted to see the trial proceed against the headwinds of Covid-19. It’s wonderful to know a cohort of 24 patients are already receiving proton beam therapy treatment for their throat cancer. We thank all involved for dealing with the challenges of set up and delivery of the trial in these extraordinary times.”

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