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Future Oncol 2021 Dec 5;17(35):4971-4982. Epub 2021 Oct 5.

Departments of Dermatology & Head & Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Locally advanced or metastatic cutaneous squamous cell carcinoma no longer amenable to surgical resection or primary radiation therapy requires an alternative approach to treatment. Until 2018, management consisted of limited systemic chemotherapies, which carried marginal clinical benefit. The introduction of immunotherapy with anti-PD-1 antibodies resulted in alternative treatment options for advanced cutaneous squamous cell carcinoma with substantial antitumor activity, durable response and acceptable safety profile. Read More

Neoplasia 2021 08 8;23(8):811-822. Epub 2021 Jul 8.

Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Carle R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address:

Developing effective therapies for the treatment of advanced head-and-neck squamous cell carcinoma (HNSCC) remains a major challenge, and there is a limited landscape of effective targeted therapies on the horizon. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a 2-electron reductase that is overexpressed in HNSCC and presents as a promising target for the treatment of HNSCC. Current NQO1-targeted drugs are hindered by their poor oxidative tolerability in human patients, underscoring a need for better preclinical screening for oxidative toxicities for NQO1-bioactivated small molecules. Read More

Int J Mol Sci 2020 Dec 29;22(1). Epub 2020 Dec 29.

Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.

In recent years, advances in drug therapy for head and neck squamous cell carcinoma (HNSCC) have progressed rapidly. In addition to cytotoxic anti-cancer agents such as platinum-based drug (cisplatin and carboplatin) and taxane-based drugs (docetaxel and paclitaxel), epidermal growth factor receptor-tyrosine kinase inhibitors (cetuximab) and immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) antibodies (nivolumab and pembrolizumab) have come to be used. The importance of anti-cancer drug therapy is increasing year by year. Read More

Front Immunol 2020 12;11:591139. Epub 2020 Nov 12.

Department of Human Oncology, University of Wisconsin, Madison, WI, United States.

In head and neck squamous cell carcinoma (HNSCC) tumors that over-expresses huEGFR, the anti-EGFR antibody, cetuximab, antagonizes tumor cell viability and sensitizes to radiation therapy. However, the immunologic interactions between cetuximab and radiation therapy are not well understood. We transduced two syngeneic murine HNSCC tumor cell lines to express human EGFR (MOC1- and MOC2-huEGFR) in order to facilitate evaluation of the immunologic interactions between radiation and cetuximab. Read More

Future Oncol 2020 Nov 11;16(32):2673-2681. Epub 2020 Aug 11.

Department of Head & Neck Medical Oncology/Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.

Esophageal cancer (EC) is the seventh most common cancer, with a poor prognosis for metastatic EC patients and limited effective drugs for treatment. Nivolumab and pembrolizumab, monoclonal antibodies that inhibit interactions of PD-1 and its ligand (PD-L1), which induce lymphocyte activation, have antitumor activity. The ATTRACTION-3 trial compared nivolumab with taxane after first-line chemotherapy and demonstrated superior overall survival (OS) for esophageal squamous cell carcinoma. Read More

Adv Otorhinolaryngol 2020 30;84:78-86. Epub 2020 Jul 30.

Unit of Oncology, University of Brescia, Brescia, Italy.

The inclusion of systemic therapy in the multimodal approach of locally advanced sinonasal cancers, at least in some selected histologies, may improve locoregional control and reduce the frequency of distant metastasis, allowing longer survival. Response to induction chemotherapy is a strong prognostic factor for a patient's outcome and it may improve disease control by surgery and radiation. Concurrent chemoradiation aims at increasing locoregional control in squamous cell cancer of the head and neck; this is particularly important in sinonasal cancers, with a risk of local relapse of about 30%. Read More

Future Oncol 2019 Sep 6;15(27):3171-3184. Epub 2019 Aug 6.

University of Texas MD Anderson Cancer Center, Department of Dermatology, Mohs and Dermasurgery Unit, Houston, TX 77030, USA.

Advanced cutaneous squamous cell carcinoma (cSCC) accounts for only 5% of all cases of cSCC but up to 60% of disease related deaths. Historically, this disease has lacked effective treatment options due to a combination of poor response rate, poor response durability and significant treatment-associated morbidity. Autumn of 2018 marked the first time ever that an agent received US FDA approval for advanced cSCC and the future is looking much brighter for this previously neglected patient population. Read More

Int J Mol Sci 2019 May 30;20(11). Epub 2019 May 30.

Service de Biochimie, Centre de Biologie Humaine (CBH), CHU Sud, 80054 Amiens, France.

Head and neck squamous cell carcinomas (HNSCC) encompass a heterogeneous group of solid tumors that arise from the upper aerodigestive tract. The tumor cells face multiple challenges including an acute demand of protein synthesis often driven by oncogene activation, limited nutrient and oxygen supply and exposure to chemo/radiotherapy, which forces them to develop adaptive mechanisms such as the Unfolded Protein Response (UPR). It is now well documented that the UPR, a homeostatic mechanism, is induced at different stages of cancer progression in response to intrinsic (oncogenic activation) or extrinsic (microenvironment) perturbations. Read More

Curr Treat Options Oncol 2019 03 14;20(4):31. Epub 2019 Mar 14.

Division of Medical Oncology, Department of Medicine, University of Washington, 825 Eastlake Ave East, Mail Stop K2-231, Seattle, WA, 98109, USA.

Opinion Statement: In a span of a few years, the surprising early successes of programmed cell death 1 (PD-1) inhibitors across a vast range of tumor types have transformed our understanding of cancer immunogenicity and provided proof of principle that T cells, if manipulated, can mediate meaningful tumor regression. In head and neck cancer, only a minority of patients respond to PD-1 therapy, but these small outcomes have fueled the enthusiasm for the next generation of immunotherapy-adoptive cell therapy-which employs recent advances in genetic engineering and cell culturing methods to generate T cells with enhanced anti-tumor efficacy for infusion back into the patient. Head and neck cancer is comprised of biologically distinct cancers, HPV-positive and HPV-negative, and the clinical responses to PD-1 inhibitors in both HPV-positive and HPV-negative head and neck patients have showcased better than any other cancer type that there are distinct pathways to immunogenicity that may lend themselves to different therapeutic approaches. Read More

Curr Treat Options Oncol 2018 10 27;19(12):68. Epub 2018 Oct 27.

UPMC Hillman Cancer Center, 5150 Centre Avenue, 5th floor, Room 552, Pittsburgh, PA, 15232, USA.

Opinion Statement: In head and neck cancer, we continue to work towards a more personalized approach to treatment of patients, where analysis of a patient's tumor guides targeting of molecular or immunologic pathways. Critically important to this pursuit is a better understanding of the direct biologic effect of a drug or combination on the tumor microenvironment in humans, as well as biomarker discovery. These goals are consistent with the primary purpose of a "window of opportunity" trial and while conduct of these trials requires a careful balance of benefits and potential risks, to date these trials have been both feasible and safe in HNSCC in the curative intent setting. Read More

Crit Rev Oncog 2018 ;23(3-4):161-171

UCLA Head and Neck Cancer Program, Jonsson Comprehensive Cancer Center, Ronald Reagan Medical Center, Los Angeles, CA, USA.

Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive disease with multiple mechanisms to impair immune-mediated recognition and control of tumor cell proliferation and metastasis. Based on successes experienced with cancer immunotherapy in the treatment of other solid tumors, considerable efforts are underway to develop immunotherapeutics that can enhance the host antitumor response to HNSCC. Promising results in preclinical studies and early clinical trials have been reported, prompting the FDA to approve the use of the immune checkpoint PD-1 receptor antagonist pembrolizumab for the treatment of platinum-refractory recurrent or metastatic HNSCC in 2016. Read More

Cancer 2018 10 6;124(19):3881-3889. Epub 2018 Oct 6.

Department of Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Background: Cetuximab combined with radiation therapy (RT) is an evidence-based treatment for locally advanced head and neck squamous cell carcinoma (HNSCC); however, locoregional failure remains the primary cause of cancer-related death in this disease. Intratumoral injection of epidermal growth factor receptor (EGFR)-antisense plasmid DNA (EGFR-AS) is safe and has been associated with promising lesional responses in patients who have recurrent/metastatic HNSCC. For the current study, the authors investigated the antitumor effects of cetuximab and EGFR-AS in preclinical HNSCC models and reported their phase 1 experience adding intratumoral EGFR-AS to cetuximab RT. Read More

J Immunother Cancer 2018 08 31;6(1):84. Epub 2018 Aug 31.

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N Broadway, 1550 Orleans St., CRB2 5M44, Baltimore, MD, 21287, USA.

Background: Low absolute lymphocyte count (ALC) has previously been established as a marker of poor prognosis in multiple cancer types. There is growing evidence that ALC may also be associated with response to immunotherapy. This study explores whether response to PD1 inhibitors in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is associated with pretreatment ALC. Read More

Swiss Med Wkly 2018 14;148:w14625. Epub 2018 May 14.

University Hospital Basel, Department of Internal Medicine, Medical Oncology, Basel, Switzerland / Cancer Immunology, Department of Biomedicine, University of Basel, Switzerland.

Head and neck squamous cell carcinoma (HNSCC) is a frequent tumour arising from multiple anatomical subsites in the head and neck region. The treatment for early-stage disease is generally single modality, either surgery or radiotherapy. The treatment for locally advanced tumours is multimodal. Read More

Eur J Cancer 2018 04 20;93:69-78. Epub 2018 Mar 20.

IIIrd Medical Department with Hematology and Medical Oncology, Paracelsus Medical University Salzburg, Salzburg, Austria; Salzburg Cancer Research Institute, Salzburg, Austria; Cancer Cluster Salzburg, Salzburg, Austria. Electronic address:

Background: Tumour heterogeneity and clonal evolution within a cancer patient are deemed responsible for relapse in malignancies and present challenges to the principles of targeted therapy, for which treatment modality is often decided based on the molecular pathology of the primary tumour. Nevertheless, the clonal architecture in distant relapse of head and neck cancer is fairly unknown.

Patients And Methods: For this project, we analysed a cohort of 386 patients within the Austrian Registry of head and neck cancer. Read More

Radiother Oncol 2017 09 31;124(3):370-378. Epub 2017 May 31.

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Germany; German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address:

Integrin-mediated cell adhesion to extracellular matrix (ECM) critically contributes to cancer cell therapy resistance and DNA double strand break (DSB) repair. c-Abl tyrosine kinase has been linked to both of these processes. Based on our previous findings indicating c-Abl hyperphosphorylation on tyrosine (Y) 412 and threonine (T) 735 upon beta1-integrin inhibition, we hypothesized c-Abl tyrosine kinase as an important mediator of beta1-integrin signaling for radioresistance. Read More

Mol Cancer Ther 2017 07 26;16(7):1257-1268. Epub 2017 Apr 26.

Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Head and neck squamous cell carcinomas (HNSCC) are frequently altered along the PI3K/AKT/mTORC signaling axis. Despite excellent preclinical data, the use of compounds targeting this pathway as monotherapy has been underwhelming in initial clinical trials, and identification of predictive biomarkers remains challenging. To investigate mTORC-specific inhibition, we tested catalytic mTORC (AZD8055) and PI3K/mTORC (NVP-BEZ-235) inhibitors ± cetuximab in a panel of HNSCC cell lines and patient-derived xenografts (PDX). Read More

Otolaryngol Clin North Am 2017 Apr;50(2):443-455

Department of Otolaryngology, University of Kansas School of Medicine, 3901 Rainbow Blvd, MS 3010, Kansas City, KS 66160, USA. Electronic address:

Cancers develop secondary to genetic and epigenetic changes that provide the cell with a survival advantage that promotes cellular immortality. Malignancy arises when tumors use mechanisms to evade detection and destruction by the immune system. Many malignancies seem to elicit an immune response, yet somehow manage to avoid destruction by the cells of the immune system. Read More

Future Oncol 2017 Mar;13(6):469-475

Department of Radiation Oncology, University of California San Francisco, CA, USA.

Future Oncol 2017 Mar;13(7):581-584

Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.

Cancer 2017 Apr 1;123(7):1259-1271. Epub 2016 Dec 1.

Cancer Therapeutics Evaluation Program.

Recent advances have permitted successful therapeutic targeting of the immune system in head and neck squamous cell carcinoma (HNSCC). These new immunotherapeutic targets and agents are being rapidly adopted by the oncologic community and hold considerable promise. The National Cancer Institute sponsored a Clinical Trials Planning Meeting to address the issue of how to further investigate the use of immunotherapy in patients with HNSCC. Read More

J Immunother Cancer 2016 15;4:83. Epub 2016 Nov 15.

Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI USA.

Background: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. Read More

Discov Med 2016 06;21(118):507-16

Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Squamous cell carcinoma is one of the most frequent tumors of the head and neck and often presents at an advanced-stage. Traditionally, treatment for head and neck squamous cell carcinoma (HNSCC) has included surgery, radiation, and chemotherapy depending on both the site and stage of disease. Although the treatment approach for local disease is often standardized, the management of recurrent and advanced disease is evolving. Read More

Curr Treat Options Oncol 2016 08;17(8):40

Department of Internal Medicine, Section of Medical Oncology, Attikon University Hospital, National Kapodistrian University of Athens, School of Medicine, 1St Rimini St, 12462, Haidari, Athens, Greece.

Opinion Statement: The discovery and antibody targeting of immune regulatory molecules such as programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathways have led to clinically meaningful anti-cancer results. Rapid advances are being made in a variety of tumor types resulting in regulatory approvals in melanoma, non small cell lung cancer, and renal cell cancer. Numerous ongoing studies are expected to establish the worth of PD-1 pathway inhibitors in other tumor types as well as in combinations with approved agents. Read More

J Egypt Natl Canc Inst 2016 Sep 6;28(3):141-8. Epub 2016 May 6.

Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India.

Head and neck squamous cell carcinoma (HNSCC) accounts for a large oncologic burden in the developing countries. In patients with locally advanced head and neck cancer multimodality treatment is warranted. Radiation therapy with concurrent chemotherapy has long been considered the standard for patients with disease involving the oropharynx, larynx and hypopharynx. Read More

Am J Clin Oncol 2016 08;39(4):396-406

Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.

Patients with squamous cell carcinoma of the head and neck (SCCHN) typically present with locally advanced (LA) stage III or IV disease and are treated with combined-modality therapy with chemotherapy, radiotherapy, and surgery (if resectable). These aggressive, upfront treatment measures are often associated with substantial morbidity, and about half the patients develop locoregional or distant recurrences. Thus, new therapeutic strategies are needed that offer similar efficacy benefits with less toxicity. Read More

Clin Cancer Res 2016 08 2;22(15):3884-93. Epub 2016 Mar 2.

Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands. Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Purpose: FGFR1 is a promising therapeutic target in multiple types of solid tumors, including head and neck squamous cell carcinoma (HNSCC). FGFR inhibitors have shown great therapeutic value in preclinical models. However, resistance remains a major setback. Read More

Mol Ther 2016 Feb 16;24(1):106-16. Epub 2015 Sep 16.

Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC.

Photodynamic therapy (PDT) is believed to promote hypoxic conditions to tumor cells leading to overexpression of angiogenic markers such as vascular endothelial growth factor (VEGF). In this study, PDT was combined with lipid-calcium-phosphate nanoparticles (LCP NPs) to deliver VEGF-A small interfering RNA (siVEGF-A) to human head and neck squamous cell carcinoma (HNSCC) xenograft models. VEGF-A were significantly decreased for groups treated with siVEGF-A in human oral squamous cancer cell (HOSCC), SCC4 and SAS models. Read More

Expert Opin Ther Targets 2015 Jun 5;19(6):795-805. Epub 2015 Feb 5.

University Hospital Heidelberg, Department of Oral and Maxillofacial Surgery , Im Neuenheimer Feld 400, 69120 Heidelberg , Germany +49 0 6221 56 38462 ; +49 0 6221 56 4222 ;

Introduction: Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by high resistance to radiotherapy, which critically depends on both altered signaling pathways within tumor cells and their dynamic interaction with the tumor microenvironment.

Areas Covered: This review covers EGFR-phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT)-mechanistic target of rapamycin (mTOR) signaling in HNSCC. The role of each pathway node in radioresistance is discussed. Read More

Cancer Lett 2015 Apr 14;359(1):65-74. Epub 2015 Jan 14.

Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan 32023, Taiwan, ROC; Center of Biomedical Technology, Chung Yuan Christian University, Taoyuan 32023, Taiwan, ROC; Center for Nanotechnology, Chung Yuan Christian University, Taoyuan 32023, Taiwan, ROC. Electronic address:

Combination therapy has become a major strategy in cancer treatment. We used anisamide-targeted lipid-calcium-phosphate (LCP) nanoparticles to efficiently deliver HIF1α siRNA to the cytoplasm of sigma receptor-expressing SCC4 and SAS cells that were also subjected to photodynamic therapy (PDT). HIF1α siRNA nanoparticles effectively reduced HIF1α expression, increased cell death, and significantly inhibited cell growth following photosan-mediated photodynamic therapy in cultured cells. Read More