‘On the rise:’ Immunotherapy options for head and neck cancer

Source: www.curetoday.com Author: Kristie L. Kahl On behalf of the Head and Neck Cancer Alliance, Dr. Michael Moore spoke with CURE® about emerging therapies that potentially offer exciting new options for the future. Although rates of head and neck cancer have risen, in part because of the human papillomavirus (HPV), emerging therapies such as targeted agents and immunotherapies are paving the way for future treatment of the disease, according to Dr. Michael Moore. “I would say (immunotherapy) is probably one of the more exciting parts of what we’ve learned about head and neck cancer in recent years,” he told CURE® as a part of its “Speaking Out” video series. On behalf of the Head and Neck Cancer Alliance, CURE® spoke with Moore, associate professor of otolaryngology-head and neck surgery and chief of head and neck surgery at Indiana University School of Medicine in Indianapolis, about targeted therapies, immunotherapy and how clinical trials are leading the way for future treatments. How have genomics and targeted therapies played a role in head and neck cancer treatment? Well, I would say it’s an emerging role. And it’s not used as commonly in head-neck cancer as it is in some other areas. So molecular testing or targeted therapies essentially are looking at a very specific part of the tumor to see if we can develop a specific drug that will target just that; (the goal is to) weaken the cancer’s defense — that is one way to say it — and try to very [...]

Henderson throat cancer patient rallies after cutting-edge treatment

Source: www.reviewjournal.com Author: Mary Hynes, Las Vegas Review-Journal In February, a cancerous tumor caused extreme swelling in Ruben Solis’ neck and face, blocking his airway. After an emergency tracheotomy, an incision to his windpipe that allowed him to breathe, Solis had to decide whether he wanted to enter a clinical trial to receive an experimental treatment. The 54-year-old Henderson resident was skeptical. But with stage 4 laryngeal cancer that had spread to his lungs, he was running out of options. Three months later, after three treatments, the tumors in his throat and lungs have dramatically shrunk and the swelling subsided. “I feel much better,” Solis said Monday. The father and grandfather, who worked in banquets and as a food and beverage manager on the Strip before falling ill, is the first person in the world to receive a combination of two experimental drugs, Enoblituzumab and Retifanlimab, as part of a new clinical trial for head and neck cancer, according to Comprehensive Cancer Centers of Nevada, the local site participating in the global study. Solis and his oncologist, Dr. Anthony Nguyen, spoke with reporters prior to the patient receiving his fourth infusion of the two drugs. The treatment is a new form of immunotherapy, which boosts the body’s immune system to combat the cancer. “So his immune system is actually being manipulated, turned on, to actually fight the cancer from inside,” Nguyen said. In this way it is different from traditional chemotherapy. “When we think of chemotherapy and cancer medicine, we [...]

Genetic changes in head and neck cancer, immunotherapy resistance identified

Source: MedicalXPress Date: April 26th, 2021 Author: University of San Diego-California A multi-institutional team of researchers has identified both the genetic abnormalities that drive pre-cancer cells into becoming an invasive type of head and neck cancer and patients who are least likely to respond to immunotherapy. "Through a series of surprises, we followed clues that focused more and more tightly on specific genetic imbalances and their role in the effects of specific immune components in tumor development," said co-principal investigator Webster Cavenee, Ph.D., Distinguished Professor Emeritus at University of California San Diego School of Medicine. "The genetic abnormalities we identified drive changes in the immune cell composition of the tumors that, in turn, dictates responsiveness to standard of care immune checkpoint inhibitors." Reporting in the April 26, 2021 online issue of the Proceedings of the National Academy of Sciences, researchers describe the role of somatic copy-number alterations—abnormalities that result in the loss or gain in a copy of a gene—and the loss of chromosome 9p in the development of human papillomavirus (HPV)-negative head and neck cancer. The loss of chromosome 9p and the deletion of JAK2 and PD-LI, two neighboring genes found on chromosome 9p, was associated with resistance to immune checkpoint inhibitors, a type of cancer immunotherapy that uses antibodies to make tumor cells visible to a patient's immune system. "Although programmed death-1 (PD-1) immune checkpoint inhibitors represent a major breakthrough in cancer treatment, only 15 percent of patients with HPV-negative head and neck cancer respond to treatment," said [...]

2021-04-27T10:01:12-07:00April, 2021|Oral Cancer News|

Cancer vaccine shows early promise across tumor types

Source: www.webmd.com Author: Walter Alexander A personalized cancer vaccine proved possible to manufacture and was well tolerated in an early phase I clinical trial, researchers said. The vaccine, known as PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or stem cell transplant. At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two could not be contacted for follow-up. Thomas Marron, MD, of Mount Sinai in New York presented these results at the American Association for Cancer Research Annual Meeting recently. “While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Marron said during his presentation. Personalized vaccines may help prime an improved immune response, he said. With this in mind, Marron and colleagues developed PGV-001, a vaccine consisting of customized peptides – a kind of amino acid -- given to patients along with initial treatment. Feasibility and safety Vaccines were given to 13 patients. Six had head and neck cancer, three had multiple myeloma – a cancer of the white blood cells -- two had lung cancer, one had breast cancer, and one had bladder cancer. Eleven patients received all 10 intended doses, and two patients received at least eight doses. “The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse [...]

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 [...]

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 [...]

Personalized vaccines: the new frontier in cancer treatment

Source: www.wildcat.arizona.edu Author: Udbhav Venkataraman Exciting results from a new clinical study showed that a personalized vaccine combined with an immunotherapy drug had a promising response rate in patients with advanced incurable head and neck cancer. Dr. Julie Bauman, chief of Hematology and Oncology at the University of Arizona College of Medicine — Tucson, led a phase one clinical trial with the pharmaceutical company, Moderna, to test the combined use of personalized vaccines created from tumor DNA with the immunotherapy drug pembrolizumab. Of the 10 patients involved in the study, five of the them responded to the treatment, meaning 30% of the cancer mass had decreased. Furthermore, two of the patients completely responded, meaning that cancer could not be detected. Molly Cassidy is one of those two patients. What was initially determined to be a stress-related ear-ache turned out to be an aggressive case of squamous cell carcinoma, a form of head and neck cancer. Head and neck cancers impact the linings of the mouth and throat. Risk factors for this disease include alcohol consumption, smoking and other environmental carcinogens that we are all exposed to. It can also be caused by human papillomavirus (HPV). Cassidy did not fit this profile at all. “I’m HPV-negative. I didn't drink. I didn't smoke. I’m a woman. I was the first person in my family to have cancer. I was 35 when I got my diagnosis,” Cassidy said. “I was also in really good health … To hear that I had cancer was [...]

2020-12-09T06:51:37-07:00December, 2020|Oral Cancer News|

Why immunotherapy only works for some with head and neck cancer

Source: medicalxpress.com Author: Katie Pence, University of Cincinnati Image of a healthy T cell on left compared to a cancer T cell on right. Credit: Ameet Chimote University of Cincinnati researchers have discovered new clues into why some people with head and neck cancer respond to immunotherapy, while others don't. Findings published in the Journal for ImmunoTherapy of Cancer show that it could all come down to "channeling" the power and function within one particular type of immune cell. Laura Conforti, Ph.D., professor in the Department of Internal Medicine at the UC College of Medicine and corresponding author on the study, says understanding these mechanisms could help in creating combination treatments to more effectively treat some patients with cancer. She points out that head and neck cancers are the sixth most common cancers in the world, affecting about 53,000 Americans every year. To combat the deadly disease, doctors often turn to immunotherapy, which boosts the body's own immune system in an effort to identify and kill cancer cells. "Our immune cells are naturally programmed to distinguish between our body's 'normal' cells and what they see as 'foreign' cells and attack only the foreign cells," explains Conforti. She says the immune cells—called T cells— lead the body's attack against cancers but the impact of that attack can be proven futile if a molecule in cancer cells is able to bind to an immune checkpoint in the T cells and effectively "turn them off like a light switch." As a [...]

2020-11-25T13:38:19-07:00November, 2020|Oral Cancer News|

Engineered killer immune cells target tumours and their immunosuppressive allies

Source: medicalxpress.com Author: eLife staff Scientists have engineered natural killer immune cells that not only kill head and neck tumor cells in mice but also reduce the immune-suppressing myeloid cells that allow tumors to evade the immune response, according to a new study in eLife. The engineered cell therapy could be used as an alternative approach for treating cancer in patients for whom previous immunotherapy based on the activation of T cells has failed. These findings are reported by researchers at the U.S. National Institutes of Health (NIH) in Bethesda, Maryland. In recent years, treatments called T-cell therapy or CAR-T cell therapy have been approved to treat blood cancers, and many others are now in development for other forms of cancer. However, these T-cell therapies rely on the ability to reprogram a patient's own T cells to express a chimeric antigen receptor (CAR) that targets tumor cells. This process of reprogramming a patient's own T cells is expensive and laborious. High affinity natural killer cells (haNKs) represent potential 'off-the-shelf' cell therapies that do not rely on reprogramming a patient's own immune cells. The same cells could be produced in mass and potentially given to anyone. But the presence of immune-suppressing myeloid cells in the tumor microenvironment remains a barrier to effective immunotherapy, including haNK cell-based treatment. To address this barrier, researchers from the NIH's National Institute on Deafness and Other Communication Disorders (NIDCD) and National Cancer Institute have utilized haNKs expressing a CAR that targets a molecule called programmed death [...]

Palbociclib plus cetuximab shows antitumor activity among head and neck cancer subset

Source: www.healio.com Author: Adkins D, et al. A combination of palbociclib and cetuximab demonstrated substantial antitumor activity among patients with platinum- or cetuximab-resistant HPV-unrelated head and neck squamous cell carcinoma, according to results of a multigroup phase 2 trial published in The Lancet Oncology. “Currently, effective therapeutic options for patients with cetuximab-resistant HNSCC are few. Traditional chemotherapy has marginal activity, with 6% of patients or fewer achieving a tumor response,” Douglas R. Adkins, MD, professor in the oncology division of the department of medicine at Washington University School of Medicine in St. Louis, and colleagues wrote. “The most effective therapy for these patients might be pembrolizumab [Keytruda, Merck] or nivolumab [Opdivo, Bristol-Myers Squibb], which have resulted in responses in 11% to 16% of patients and median OS of 6.9 months to 8 months. Novel treatment strategies are needed for patients with recurrent or metastatic HNSCC.” The combination of the cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib (Ibrance, Pfizer) and epidermal growth factor receptor inhibitor cetuximab (Erbitux, Eli Lilly) appeared safe and tolerable in the phase 1 portion of the multicenter trial, conducted across eight U.S. university sites. For phase 2, Adkins and colleagues divided 62 patients with HPV-unrelated HNSCC (median age, 66 years; interquartile range [IQR], 58-70; 71% men) into two groups: those who were platinum-resistant (group 1; n = 30) and those who were resistant to cetuximab (group 2; n = 32). Primary tumor sites included the oral cavity (42%) and larynx (29%), and 81% of patients had received one [...]

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