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Cancers
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Precision Medicine for Head and Neck Cancer
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Precision Medicine for Head and Neck Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 10804

Special Issue Editor

Dr. J. Chad Brenner

E-Mail Website
Guest Editor
Department of Otolaryngology—Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Interests: genetics; immunotherapy; liquid biopsies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Over the past several years, precision medicine approaches have evolved rapidly to not only incorporate targetable genetic lesions and compassionate care use of targeted therapies in advanced cancer settings, but also to utilize more complex pre-treatment molecular and cellular information in attempts to improve early cancer care. Further, due to the ability to detect both Epstein Barr virus and human papilloma virus in circulation, the head and neck field has been one of the leaders in moving towards incorporating real-time liquid biopsies to inform on both the effectiveness of treatment and the potential of early recurrence. Thus, when combined with the recent immunotherapy approvals in this space, head and neck precision medicine is at the forefront of this rapidly evolving field and may help provide insight into both the utility and barriers to utilizing these emerging approaches more broadly in other cancers. 

Dr. J. Chad Brenner
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • targeted therapy
  • ctDNA
  • adaption

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Published Papers (4 papers)

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Research

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21 pages, 3264 KiB  
Article
Combined Inhibition of IAPs and WEE1 Enhances TNFα- and Radiation-Induced Cell Death in Head and Neck Squamous Carcinoma
by Tiffany Toni, Ramya Viswanathan, Yvette Robbins, Sreenivasulu Gunti, Xinping Yang, Angel Huynh, Hui Cheng, Anastasia L. Sowers, James B. Mitchell, Clint T. Allen, Ethan L. Morgan and Carter Van Waes
Cancers 2023, 15(4), 1029; https://doi.org/10.3390/cancers15041029 - 6 Feb 2023
Cited by 6 | Viewed by 2511
Abstract
Head and neck squamous cell carcinoma (HNSCC) remains a prevalent diagnosis with current treatment options that include radiotherapy and immune-mediated therapies, in which tumor necrosis factor-α (TNFα) is a key mediator of cytotoxicity. However, HNSCC and other cancers often display TNFα resistance due [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) remains a prevalent diagnosis with current treatment options that include radiotherapy and immune-mediated therapies, in which tumor necrosis factor-α (TNFα) is a key mediator of cytotoxicity. However, HNSCC and other cancers often display TNFα resistance due to activation of the canonical IKK–NFκB/RELA pathway, which is activated by, and induces expression of, cellular inhibitors of apoptosis proteins (cIAPs). Our previous studies have demonstrated that the IAP inhibitor birinapant sensitized HNSCC to TNFα-dependent cell death in vitro and radiotherapy in vivo. Furthermore, we recently demonstrated that the inhibition of the G2/M checkpoint kinase WEE1 also sensitized HNSCC cells to TNFα-dependent cell death, due to the inhibition of the pro-survival IKK-NFκB/RELA complex. Given these observations, we hypothesized that dual-antagonist therapy targeting both IAP and WEE1 proteins may have the potential to synergistically sensitize HNSCC to TNFα-dependent cell death. Using the IAP inhibitor birinapant and the WEE1 inhibitor AZD1775, we show that combination treatment reduced cell viability, proliferation and survival when compared with individual treatment. Furthermore, combination treatment enhanced the sensitivity of HNSCC cells to TNFα-induced cytotoxicity via the induction of apoptosis and DNA damage. Additionally, birinapant and AZD1775 combination treatment decreased cell proliferation and survival in combination with radiotherapy, a critical source of TNFα. These results support further investigation of IAP and WEE1 inhibitor combinations in preclinical and clinical studies in HNSCC. Full article
(This article belongs to the Special Issue Precision Medicine for Head and Neck Cancer)
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14 pages, 370 KiB  
Article
Phase II Trial of CDX-3379 and Cetuximab in Recurrent/Metastatic, HPV-Negative, Cetuximab-Resistant Head and Neck Cancer
by Julie E. Bauman, Ricklie Julian, Nabil F. Saba, Trisha M. Wise-Draper, Douglas R. Adkins, Paul O’Brien, Mary Jo Fidler, Michael K. Gibson, Umamaheswar Duvvuri, Margo Heath-Chiozzi, Diego Alvarado, Richard Gedrich, Philip Golden and Roger B. Cohen
Cancers 2022, 14(10), 2355; https://doi.org/10.3390/cancers14102355 - 10 May 2022
Cited by 7 | Viewed by 2649
Abstract
In phase I development, CDX-3379, an anti-ErbB3 monoclonal antibody, showed promising molecular and antitumor activity in head and neck squamous cell carcinoma (HNSCC), alone or in combination with cetuximab. Preliminary biomarker data raised the hypothesis of enhanced response in tumors harboring FAT1 mutations. [...] Read more.
In phase I development, CDX-3379, an anti-ErbB3 monoclonal antibody, showed promising molecular and antitumor activity in head and neck squamous cell carcinoma (HNSCC), alone or in combination with cetuximab. Preliminary biomarker data raised the hypothesis of enhanced response in tumors harboring FAT1 mutations. This phase II, multicenter trial used a Simon 2-stage design to investigate the efficacy of CDX-3379 and cetuximab in 30 patients with recurrent/metastatic, HPV-negative, cetuximab-resistant HNSCC. The primary endpoint was objective response rate (ORR). Secondary endpoints included ORR in patients with somatic FAT1 mutations, progression-free survival (PFS), overall survival (OS), and safety. Thirty patients were enrolled from March 2018 to September 2020. The ORR in genomically unselected patients was 2/30 (6.7%; 95% confidence interval [CI], 0.8–22.1). Median PFS and OS were 2.2 (95% CI: 1.3–3.6) and 6.6 months (95% CI: 2.7–7.5), respectively. Tissue was available in 27 patients including one of two responders. ORR was 1/10 (complete response; 10%; 95% CI 0.30–44.5) in the FAT1-mutated versus 0/17 (0%; 95% CI: 0–19.5) in the FAT1-wildtype cohorts. Sixteen patients (53%) experienced treatment-related adverse events (AEs) ≥ grade 3. The most common AEs were diarrhea (83%) and acneiform dermatitis (53%). Dose modification was required in 21 patients (70%). The modest ORR coupled with excessive, dose-limiting toxicity of this combination precludes further clinical development. Dual ErbB3-EGFR inhibition remains of scientific interest in HPV-negative HNSCC. Should more tolerable combinations be identified, development in an earlier line of therapy and prospective evaluation of the FAT1 hypothesis warrant consideration. Full article
(This article belongs to the Special Issue Precision Medicine for Head and Neck Cancer)
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12 pages, 923 KiB  
Article
Radiotherapy Is Associated with an Accelerated Risk of Carotid Atherosclerosis in Patients with Nasopharyngeal Carcinoma: A Nine-Year Prospective Follow-Up Study
by Cheng-Hsien Lu, Yun-Ru Lai, Fu-Min Fang, Teng-Yeow Tan, Wen-Chan Chiu, Dong-Yi Hsieh, Chih-Cheng Huang, Chia-Yi Lien, Ben-Chung Cheng, Chih-Yen Chien, Tai-Lin Huang and Chia-Te Kung
Cancers 2022, 14(5), 1234; https://doi.org/10.3390/cancers14051234 - 27 Feb 2022
Cited by 5 | Viewed by 2147
Abstract
Radiation-related extracranial vasculopathy is a common late effect after radiation in patients with nasopharyngeal carcinoma (NPC). We proposed the hypothesis that radiation-related extracranial vasculopathy is a progressive process that can begin immediately after radiotherapy and persist for a longer period, and inflammation and [...] Read more.
Radiation-related extracranial vasculopathy is a common late effect after radiation in patients with nasopharyngeal carcinoma (NPC). We proposed the hypothesis that radiation-related extracranial vasculopathy is a progressive process that can begin immediately after radiotherapy and persist for a longer period, and inflammation and oxidative stress may play a pivotal role in this process. Thirty-six newly diagnosed NPC patients were assessed with B-mode ultrasound for the common carotid artery (CCA) intima media thickness (IMT) measurement as well as surrogate markers at three different stages (baseline, immediately after concurrent chemoradiation therapy (CCRT), and 9 years after enrollment). A healthy control group was also recruited for comparison. Surrogate markers including a lipid profile, HbA1c, inflammation, oxidative stress, and platelet activation markers were assessed. The mean CCA IMT in the NPC group were increased immediately after CCRT (p = 0.043). The mean CCA IMT value after a 9-year follow-up also showed a significant increase in NPC and control group, respectively (p < 0.0001 and p < 0.0001, paired t test). The annual increase mean CCA IMT (mm) was 0.053 ± 0.025 and 0.014 ± 0.013 in NPC and control group, respectively (p < 0.0001). The baseline high sensitivity CRP (hs-CRP), thiol, TBARS, and CD63 level were significantly higher in the NPC group (hs-CRP, p = 0.001, thiol, p < 0.0001, TBARS, p = 0.05, and CD63 level, p = 0.04). The thiol and TBARS levels were significantly lower in NPC patients immediately after CCRT (thiol, p < 0.0001, and TBARS, p = 0.043). The CD62P level was significantly higher while the thiol level was significantly lower in the NPC group after a 9-year follow-up (CD62P level, p = 0.007; and thiol level, p = 0.004). Radiation-related extracranial vasculopathy is a progressive process that begins immediately after radiotherapy with significantly increased carotid IMT compared to the control group during the 9-year follow-up. Chronic inflammation and oxidative stress might serve to drive the process and also contribute to increased platelet activation. Full article
(This article belongs to the Special Issue Precision Medicine for Head and Neck Cancer)
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Review

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19 pages, 650 KiB  
Review
Intraoperative In Vivo Imaging Modalities in Head and Neck Cancer Surgical Margin Delineation: A Systematic Review
by Kurtis Young, Enze Ma, Sameer Kejriwal, Torbjoern Nielsen, Sukhkaran S. Aulakh and Andrew C. Birkeland
Cancers 2022, 14(14), 3416; https://doi.org/10.3390/cancers14143416 - 14 Jul 2022
Cited by 7 | Viewed by 2389
Abstract
Surgical margin status is one of the strongest prognosticators in predicting patient outcomes in head and neck cancer, yet head and neck surgeons continue to face challenges in the accurate detection of these margins with the current standard of care. Novel intraoperative imaging [...] Read more.
Surgical margin status is one of the strongest prognosticators in predicting patient outcomes in head and neck cancer, yet head and neck surgeons continue to face challenges in the accurate detection of these margins with the current standard of care. Novel intraoperative imaging modalities have demonstrated great promise for potentially increasing the accuracy and efficiency in surgical margin delineation. In this current study, we collated and analyzed various intraoperative imaging modalities utilized in head and neck cancer to evaluate their use in discriminating malignant from healthy tissues. The authors conducted a systematic database search through PubMed/Medline, Web of Science, and EBSCOhost (CINAHL). Study screening and data extraction were performed and verified by the authors, and more studies were added through handsearching. Here, intraoperative imaging modalities are described, including optical coherence tomography, narrow band imaging, autofluorescence, and fluorescent-tagged probe techniques. Available sensitivities and specificities in delineating cancerous from healthy tissues ranged from 83.0% to 100.0% and 79.2% to 100.0%, respectively, across the different imaging modalities. Many of these initial studies are in small sample sizes, with methodological differences that preclude more extensive quantitative comparison. Thus, there is impetus for future larger studies examining and comparing the efficacy of these intraoperative imaging technologies. Full article
(This article belongs to the Special Issue Precision Medicine for Head and Neck Cancer)
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