American Head & Neck Society

Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.

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AHNS Virtual Education Series

Management of Salivary Malignancy

Instructional Course: Management of Salivary Malignancy Case Based Panel Discussion

Date: Wednesday, December 9, 2020

Time: 4:00 PM Pacific /6:00 PM Central / 7:00 PM Eastern
Session is an hour long

Complimentary to all attendees

Register Here

Learning Objective:

At the conclusion of this webinar, participants will be able to:

  1. Recognize common areas of controversy in the management of salivary malignancy
  2. Prioritize therapeutic options for salivary malignancy that maximizes benefit and minimizes harm
  3. Plan appropriate reconstruction after ablative surgery for salivary malignancy

Faculty:

Moderator: David Cognetti, MD, Thomas Jefferson University

Panelists:
Cecelia Schmalbach, MD MSc FACS, Temple University
Kiran Kakarala, MD, University of Kansas
William Ryan, MD, University of California, San Francisco

Published on by AHNS Webmaster

AHNS Virtual Education Series

Management of Salivary Malignancy

Instructional Course: Management of Salivary Malignancy Case Based Panel Discussion

Date: Wednesday, December 9, 2020

Time: 4:00 PM Pacific /6:00 PM Central / 7:00 PM Eastern
Session is an hour long

Complimentary to all attendees

Register Here

Learning Objective:

At the conclusion of this webinar, participants will be able to:

  1. Recognize common areas of controversy in the management of salivary malignancy
  2. Prioritize therapeutic options for salivary malignancy that maximizes benefit and minimizes harm
  3. Plan appropriate reconstruction after ablative surgery for salivary malignancy

Faculty:

Moderator: David Cognetti, MD, Thomas Jefferson University

Panelists:
Cecelia Schmalbach, MD MSc FACS, Temple University
Kiran Kakarala, MD, University of Kansas
William Ryan, MD, University of California, San Francisco

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AHNS Grants– Letter of Intent (LOI) Deadline: Tuesday, December 15, 2020 11:59 ET

Dear AHNS members,

The American Head and Neck Society will sponsor nine research grants for 2021 which are available through American Academy of Otolaryngology CORE. The Letters of Intent (LOI) for the Grants are due by 11:59 EST on Tuesday, December 15, 2020.

  1. AHNS.AAO-HNSF Young Investigator Combined Award – Open to fellows and assistant professors. Must be AHNS member (may be candidate member). To support research in neoplastic disease of the head and neck. Up to two years, $20,000 per year. One award available per year.
  2. AHNS/AAO-HNSF Translational Innovator Award – Applicants must have completed residency or fellowship training in seven years or less prior to submitting application. Candidates need to have demonstrated the capacity or potential for a highly productive independent research career with an emphasis in head and neck surgical oncology. Two years, non-renewable, $80,000 maximum ($40,000 per year), one available annually.
  3. AHNS Pilot Grant – Open to Medical Students, residents, PhD, and Junior Faculty residing in the U.S. or Canada to support basic, translational, or clinical research projects in head and neck oncology. One year, $10,000.00. One award available this year.
  4. AHNS Ballantyne Resident Research Pilot Grant – for best grant application by a resident, this award utilizes the same forms and guidelines as the pilot grant (above). One year, non-renewable, $10,000 maximum total costs. One award available per year. The top ranked pilot award will be honored as the Ballantyne Award.
  5. AHNS Endocrine Surgery Section Eisai Research Award – Open to medical students focusing in otolaryngology, otolaryngology residents, PhDs or faculty members in otolaryngology departments. Research topics must relate to endocrine surgery or disease. Preference will be given to early-stage investigators (10 years or less from a terminal degree or fellowship training) or more experienced researchers pursuing a new line of inquiry for which pilot data are needed. One year, $10,000.00. One award available this year.
  6. AHNS Endocrine Surgery Section Stryker Research Grant – Open to medical students focusing in otolaryngology, otolaryngology residents, PhDs or faculty members in otolaryngology departments. Research topics must relate to endocrine surgery or disease. Preference will be given to early-stage investigators (10 years or less from a terminal degree or fellowship training) or more experienced researchers pursuing a new line of inquiry for which pilot data are needed. One year, $10,000.00. One award available this year.
  7. AHNS Presidential Request for Application Pilot Award on Mucosal Head and Neck Cancer Research – Open to all otolaryngology-head and neck surgery residents, fellows, and faculty. Previous AHNS or AAO-HNS Foundation research grant recipients are eligible to compete for this grant. However, candidates who have successfully obtained funding from a private, institutional, or federal funding agency for the same research are ineligible. Candidates who have applied for support of the same research from other funding sources, and who are notified of an award from both another agency and from AHNS must choose only one of the awards. One year, $10,000. One award available.
  8. AHNS Presidential Request for Application Pilot Award on Salivary Gland Cancer Research – Open to active AHNS members, or trainees (ACGME-accredited otolaryngology residents or AHNS-accredited head and neck surgery fellows) sponsored by an AHNS member can apply. Previous AHNS or AAO-HNS Foundation research grant recipients are eligible to compete for this grant. However, candidates who have successfully obtained funding from a private, institutional, or federal funding agency for the same research are ineligible. Candidates who have applied for support of the same research from other funding sources, and who are notified of an award from both another agency and from AHNS must choose only one of the awards. One year, $10,000. One award available.
  9. AHNS Presidential Request for Application Pilot Award on Basic and Translational Research – This high risk, high reward grant is open to early or mid-career investigators who are AHNS members in good standing. Previous AHNS or AAO-HNS Foundation research grant recipients are eligible to compete for this grant. However, candidates who have successfully obtained funding from a private, institutional, or federal funding agency for the same research are ineligible. Candidates who have applied for support of the same research from other funding sources, and who are notified of an award from both another agency and from AHNS must choose only one of the awards. One year, $10,000. One award available.

You may find general information about the AHNS grants by visiting the website: https://www.ahns.info/research/grants/

Applicants interested in applying for the AHNS grants must submit their applications through the Academy CORE (combined otolaryngologic research evaluation) process. Letters of intent and applications are paperless and submitted through proposal Central.

Reminder: You must complete the Letter of Intent before submitting the full grant. You will not be penalized if you submit an LOI and decide not to complete a full grant.

 

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AHNS Basic Science/Translational Newsletter Vol 5

Summary of Loss of p53 Drives Neuron Reprogramming In Head and Neck Cancer

Moran Amit, Hideaki Takahashi, Mihnea Paul Dragomir, Antje Lindemann, Frederico O Gleber-Netto, Curtis R Pickering, Simone Anfossi, Abdullah A Osman, Yu Cai, Rong Wang, Erik Knutsen, Masayoshi Shimizu, Cristina Ivan, Xiayu Rao, Jing Wang, Deborah A Silverman, Samantha Tam, Mei Zhao, Carlos Caulin, Assaf Zinger, Ennio Tasciotti, Patrick M Dougherty, Adel El-Naggar, George A Calin, Jeffrey N Myers.

From Nature, February 2020; 578(7795):449-454.

Article Review by Moran Amit, MD, PhD and  Patrick J. Hunt, MD, PhD

Background / Hypothesis
Solid tumors are complex collections of cells that are encircled by benign cells that both influence and are influenced by the tumor. These surrounding cells, known as the tumor microenvironment, include vasculature, immune cells, neurons, and other cell types. Tumors manipulate these nearby cells in ways that benefit the tumor. Autonomic neurons have been shown to innervate and drive malignant growth in a variety of solid tumors, including head and neck, prostate, breast, and gastric cancers. However, the mechanisms by which these neuron-tumor relationships are formed are not well understood. In this study, we hypothesized that the trophic relationships between oral cavity squamous cell carcinomas (OCSCCs) and nearby autonomic neurons arise through direct signaling between the tumors and local neurons.

Design
This study was conducted using several laboratory models. OCSCC progression was modeled in mice by genetic knockout of the Trp53 gene (encoding the p53 protein) combined with administration of the carcinogen 4-nitroquinoloine 1-oxide (4NQO), which mimics the genetic alterations associated with tobacco use. Additional studies were conducted in cell culture models in which p53-deficient cells were co-cultured with mouse trigeminal ganglia neurons. Xenograft models were also used, in which OCSCC cells were injected directly into the oral cavities of mice. Using these models, we examined changes in the cellular composition of the tumor microenvironment and in changes in microRNA expression in cancer cells, and the effects that these changes had on the tumors and associated neurons.

Summary of Results
Loss of p53 expression in OCSCC tumors resulted in increased nerve density within the tumors. This neuritogenesis was controlled by shuttling of tumor-derived microRNAs via extracellular vesicles. The microRNAs within these extracellular vesicles were primarily responsible for regulating the observed axonogenesis. Of these vesicular microRNAs, miR-34a acted s a major restrictive factor for neuritogenesis, whereas miR-21 and miR-324 activity promoted neural reprogramming and neuritogenesis. Moreover, the neurons innervating p53-deficient OCSCC tumors acquired adrenergic features through transdifferentiation of trigeminal sensory nerve fibers. This transdifferentiation process corresponded with increased expression of neuron-reprogramming transcription factors, including POU5F1, KLF4, and ASCL1, which are overexpressed in p53-deficient samples and are candidate targets of miR-34a regulation. In OCSCC samples from human patients, increased expression of tyrosine hydroxylase, a marker of adrenergic neurons, was strongly associated with poor outcomes, thereby demonstrating the relevance of these findings in human patients with cancer.

Strengths

  • Rigorous basic science experimentation in highly validated models.
  • Novel discovery of a cancer-driven mechanism regulating increased neuritogenesis and neurotype switching.
  • Delineation of a clear path towards using extracellular vesicle samples as
    biomarkers of disease and microRNAs as targets of anticancer therapies.
  • Direct relevance to human patients with OCSCCs

 Weaknesses

  • Human evidence is based on association—a follow up study therapeutically targeting the adrenergic neurons innervating OCSCCs would be informative.
  • Proteins and other small molecules within the extracellular vesicles might also be important for the growth and spread of both neurons and tumors.

Key Points

  • OCSCC tumors deficient in p53 demonstrate increased adrenergic innervation. This increased adrenergic innervation is associated with poor outcomes in a variety of human cancers. Until this study, the mechanisms that drive this phenomenon were unknown.
  • Extracellular vesicles derived from p53-deficient OCSCC cells carry numerous microRNAs, including miR-21 and miR-324, which both act to increase neuritogenesis in nearby neurons.
  • Retrograde molecular signaling from p53-deficient tumors drives neural transdifferentiation of trigeminal sensory neurons to an adrenergic neurotype.  This increased adrenergic activity subsequently drives increased tumor growth.
  • Increased expression of adrenergic markers in human OCSCC biopsy samples is associated with poor survival in patients. This finding, combined with these newly uncovered mechanisms, strongly suggests avenues for future therapies to diagnose and treat patients with cancer.

From the Basic Science/Translational Service
Jeffrey C. Liu MD Vice Chair
Richard Wong MD Chair

Moran Amit

Moran Amit

Dr. Amit is dedicated to key areas of cancer research that will develop therapeutic approaches to improve patients’ survival, treatment responses, and quality of life. During his residency training, Dr. Amit became interested in the biology of cancer. After completing his residency, he undertook further training in Head and Neck Surgical Oncology at The University of Texas MD Anderson Cancer Center, where he completed a clinical fellowship as a head and neck surgical oncologist and a postdoctoral fellowship with a focus on the neurobiology of cancer. Dr. Amit was recruited to the Department of Head and Neck Surgical Oncology at MD Anderson in April 2019 and has an active research laboratory focusing on cancer-related neurogenesis and axonogenesis and on the role of neuro-immunology in cancer. One exciting finding of Dr. Amit’s lab involved describing a mechanism by which head and neck tumors can reprogram adrenergic signaling in neurons and the effect of targeting the peripheral nervous system on cancer initiation and progression. This will serve as a basis for combining treatments targeting the nervous system with other therapies, such as immunotherapy, in the treatment of head and neck cancers. Dr. Amit is continuing his work by building a team to study how the neural microenvironment affects responses to chemotherapy and immunotherapy in patients with non-melanoma skin cancer and other cancers, and to develop novel strategies to combat resistance to these therapies.
Moran Amit

Latest posts by Moran Amit (see all)

Patrick Hunt

Patrick Hunt

Patrick J. Hunt is an MD-PhD candidate in the Baylor College of Medicine Medical Scientist Training Program and the University of Texas MD Anderson Cancer Center Department of Neurosurgery. His research and clinical interests include understanding neural mechanisms of mammalian feeding control, developing functional neurosurgical approaches to treatment refractory illnesses, and improving outcomes in skull base surgeries.
Patrick Hunt

Latest posts by Patrick Hunt (see all)

 

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AHNS 2021 International Conference – Submit Your Abstracts

AHNS Call For Abstracts

 Submission Deadline:

December 4, 2020 – 5:00 PM PT

You are invited to submit abstracts to the AHNS 10th International Conference on Head and Neck Cancer: “Survivorship through Quality and Innovation” taking place on July 22-25, 2021 at the Hyatt Regency Chicago in Chicago, Illinois.

All abstracts, even if previously submitted and accepted will undergo the standard peer review process. Please submit new or previously submitted abstracts for the conference next summer, as long as it complies with the following paragraph. 

  • No Previously Published/Presented Submissions (Encore Abstracts):The abstract submitted must present original work that has not and will not be published or presented prior to the AHNS 10th International Conference on Head and Neck Cancer, and shall not be under review for publication prior to the AHNS 10th International Conference on Head and Neck Cancer except by permission from the AHNS Program Chair. The exception to this rule is that a manuscript may be submitted to JAMA Otolaryngology – Head & Neck Surgery for special meeting related consideration only after the abstract has been accepted by AHNS for presentation. 

To submit your abstracts, please visit the following web page:

 Submit Your Abstract Here Now 

  • NOTE: ALL content authors are required to disclose any financial relationship(s) with an ACCME-defined commercial interest (“industry”). AHNS considers the presenter of a proffered paper to be in control of the content. Thus, employees of commercial interests may not be the presenter for abstracts submitted to AHNS meetings.

If you have any questions, please contact the AHNS office at 310-437-0559 x 118 or by email at [email protected].