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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 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

Int J Radiat Biol 2014 Aug 3;90(8):678-86. Epub 2014 Apr 3.

OncoRay - National Center for Radiation Research in Oncology, Medizinische Fakultät Carl Gustav Carus.

Purpose: Epidermal growth factor receptor (EGFR) is critically involved in progression and therapy resistance of squamous cell carcinoma (SCC). Albeit EGFR targeting could improve the effect of radiotherapy on patients' outcome, the clinical results failed to meet expectations from preclinical studies. In this work, we evaluated the potential of the radionuclide Yttrium-90 ((90)Y) bound to Cetuximab ((90)Y-Cetuximab) as novel targeting approach for SCC cells in vitro. Read More

Int J Clin Oncol 2014 Apr 28;19(2):220-9. Epub 2014 Feb 28.

Department of Otolaryngology, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan,

The multidisciplinary approach is becoming the standard for treatment of advanced head and neck cancer. Combined modality treatment preserves quality of life as well as improving the length of survival time. Molecular targeted drugs have become very important in the multidisciplinary approach for the treatment of advanced head and neck cancer. Read More

Pharmacol Ther 2014 Apr 23;142(1):88-98. Epub 2013 Nov 23.

Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address:

Approximately 600,000 new cases of head and neck cancer arise worldwide each year. Of these, a large majority are head and neck squamous cell carcinomas (HNSCC). Conventional treatments, including surgical excision followed by radiation and/or chemoradiotherapy have limited efficacy and are associated with substantial toxicity. Read More

Indian J Dent Res 2013 Mar-Apr;24(2):261-6

Department of Oral Medicine and Radiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India.

The majority of patients with head and neck cancer present with locally advanced disease. Locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) poses one of the most complex management challenges. This stage of disease is still potentially curable, but requires combined-modality therapy. Read More

Clin Cancer Res 2013 Jul 2;19(14):3808-19. Epub 2013 May 2.

Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland 20892, USA.

Purpose: Phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway activation is often associated with altered expression or mutations of PIK3CA, TP53/p73, PTEN, and TGF-β receptors (TGFBR) in head and neck squamous cell carcinomas (HNSCC). However, little is known about how these alterations affect response to PI3K/mTOR-targeted agents.

Experimental Design: In this preclinical study, PI3K/Akt/mTOR signaling was characterized in nine HNSCC (UM-SCC) cell lines and human oral keratinocytes. Read More

BMC Cancer 2012 Oct 10;12:463. Epub 2012 Oct 10.

Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

Background: Only a minority of cancer patients benefits from the combination of EGFR-inhibition and radiotherapy in head and neck squamous cell carcinoma (HNSCC). A potential resistance mechanism is activation of EGFR and/or downstream pathways by stimuli in the microenvironment. The aim of this study was to find molecular targets induced by the microenvironment by determining the in vitro and in vivo expression of proteins of the EGFR-signaling network in 6 HNSCC lines. Read More

Otolaryngol Pol 2012 Sep-Oct;66(5):307-12. Epub 2012 Jul 2.

Department of Thoracic Surgery Medical University of Lublin, Poland.

Head and neck cancers (HNC) are 6th most common malignancies according to the incidence rate. Over 85% of tumors of this region are epithelial tumors, especially squamous cell carcinomas (head and neck squamous cell carcinomas - HNSCC). Surgery, chemotherapy and radiotherapy are still the standard for the treatment of HNC. Read More

Laryngorhinootologie 2012 Mar 28;91 Suppl 1:S123-43. Epub 2012 Mar 28.

Hals-Nasen-Ohrenklinik, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen. thomas.hoff

Head and neck cancers, most of which are squamous cell tumours, have an unsatisfactory prognosis despite intensive local treatment. This can be attributed, among other factors, to tumour recurrences inside or outside the treated area, and metastases at more distal locations. These tumours therefore require not only the standard surgical and radiation treatments, but also effective systemic treatment. Read More

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2011 Jun;46(6):505-8

Department of Otorhinolaryngology Head and Neck Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China.

Objective: To investigate the prevalence and treatment of oral mucositis caused by concurrent chemoradiotherapy and/or molecular targeted therapy in the patients with advanced squamous cell carcinoma of the head and neck.

Methods: A retrospective study of the incidence and treatment of oral mucositis was performed in 179 patients (155 male and 24 female;124 patients at stage III and 55 patients at stage IV) receiving concurrent chemotherapy and (or) molecular targeted therapy between November 2007 and November 2010. Grade I, II, III and IV oral mucositis occurred respectively in 49, 50, 67 and 13 patients. Read More

Asia Pac J Clin Oncol 2011 Sep;7(3):236-51

Division of Cancer Services, Princess Alexandra Hospital, Brisbane, Australia.

Over the past three decades there has been a move toward organ preservation protocols in the management of locally advanced mucosal head and neck squamous cell carcinomas (LAHNSCC) with combinations of radiotherapy (RT), chemotherapy and, more recently, biological agents. Current standard chemoradiation strategies have reached the upper limits of toxicity. In addition, the traditional one size fits all approach of grouping patients according to traditional clinicopathological features fails to take into account the vast underlying biological heterogeneity of tumors and their host. Read More

Cancer Res 2011 Jul 13;71(13):4598-607. Epub 2011 May 13.

Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga, Japan.

RECQL1 and WRN proteins are RecQ DNA helicases that participate in suppression of DNA hyper-recombination and repair. In this study, we report evidence supporting their candidacy as cancer therapeutic targets. In hypopharyngeal carcinomas, which have the worst prognosis among head and neck squamous cell carcinomas (HNSCC) that are rapidly rising in incidence, we found that RECQL1 and WRN proteins are highly expressed and that siRNA-mediated silencing of either gene suppressed carcinoma cell growth in vitro. Read More

Anticancer Drugs 2011 Aug;22(7):656-64

Department of Otolaryngology, School of Medicine, University of Pittsburgh, Pennsylvania, USA.

Head and neck squamous cell cancer is the sixth most common cancer in the world. Despite advances in combined modality therapy, poor outcomes continue to be observed in the form of locoregional recurrence, metastasis, and development of second primary tumors. As tumors vary in their molecular and genetic etiology and because often there is already deregulation at the molecular level in otherwise histopathologically normal tissue, risk stratification using clinical and pathologic criteria alone has proved to be inadequate. Read More

Anticancer Drugs 2011 Aug;22(7):613-20

Radiotherapy Unit, Cancerology Regional University Henry S. Kaplan Center of Tours, Bretonneau Hospital, Tours, France.

Five hundred and fifty thousand new head and neck cancer cases are diagnosed each year worldwide. They are mostly locally advanced squamous cell carcinoma with a poor prognosis in terms of locoregional and distant failure. A major challenge for patients with locally advanced squamous cell carcinoma is to achieve a high cure rate while preserving functions. Read More

Bull Cancer 2010 Dec;97(12):1453-66

Institut Curie, 26, rue d'Ulm, 75248 Paris cedex 05, France.

The emergence of molecularly targeted therapy did not spare head and neck cancers. Head and neck squamous cell carcinomas (HNSCC) were indeed one of the first tumor types to get a molecularly targeted agent approved (cetuximab, a monoclonal antibody targeting EGFR), not only in the recurrent or metastatic setting but also in the locally advanced setting. However, the development of molecularly targeted agents inhibiting non-EGFR targets appears to be complex. Read More

Curr Opin Oncol 2010 May;22(3):212-20

Drug Development Program, Princess Margaret Hospital, Toronto, Ontario, Canada.

Purpose Of Review: This article reviewed the recent developments in molecular targeted therapy in head and neck cancers. A brief summary of other pathways of interest is also enclosed.

Recent Findings: The use of cetuximab in squamous cell head and neck cancer is associated with clinical benefit and, in some cases, survival. Read More

Mol Cancer Ther 2009 Aug 22;8(8):2255-65. Epub 2009 Jul 22.

Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.

To determine if the mammalian target of rapamycin (mTOR) inhibitor CCI-779 can sensitize head and neck squamous cell carcinoma (HNSCC) to radiotherapy (XRT) and compare the radiosensitizing effects to cisplatin with its known considerable toxicity. Radiosensitizing effects of CCI-779 were assayed on HNSCC cell lines in vitro. CCI-779 (5 mg/kg), cisplatin (1 mg/kg), and XRT (2 Gy) alone and in combination were evaluated for antitumor activity in mice bearing FaDu and SCC40 xenografts. Read More

Nat Rev Clin Oncol 2009 May;6(5):266-77

Department of Radiation Oncology, Genolier Swiss Medical Network, Genolier, Switzerland.

Therapeutic management of locally advanced, recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is often limited by a rather unfavorable efficacy and toxicity ratio. Since the 1990s, targeted molecular therapy has been extensively investigated both as a single modality and in combination with cytotoxic treatments, such as radiotherapy or chemotherapy. EGFR is commonly over expressed in HNSCC and is an attractive molecular target. Read More

Hematol Oncol Clin North Am 2008 Dec;22(6):1193-208, ix

Department of Radio-Oncology, Genolier Swiss Medical Network, CH 1272 Genolier, Switzerland.

Molecular markers will become increasingly important in directing treatment approaches in locally advanced squamous cell carcinomas of the head and neck (HNSCC). Several predictive markers have been identified that may be useful for selecting tumors most likely to respond to radiotherapy or chemotherapy. However, few markers have potential as therapeutic targets. Read More

ScientificWorldJournal 2008 Sep 21;8:909-19. Epub 2008 Sep 21.

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Cancers of the head and neck and of the lung are associated with high morbidity and mortality rates that have remained relatively unchanged for more than 3 decades, despite advances in radiation therapies and chemotherapies over the same time. It is generally believed that the efficacy of standard therapy regimens has reached a plateau for these cancers. The discovery of specific aberrant molecular signaling pathways in solid tumors has afforded promising new directions for newer "targeted" cancer therapeutics. Read More

Lancet 2008 May;371(9625):1695-709

Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15232, USA.

Most head and neck cancers are squamous cell carcinomas that develop in the upper aerodigestive epithelium after exposure to carcinogens such as tobacco and alcohol. Human papillomavirus has also been strongly implicated as a causative agent in a subset of these cancers. The complex anatomy and vital physiological role of the tumour-involved structures dictate that the goals of treatment are not only to improve survival outcomes but also to preserve organ function. Read More

Gan To Kagaku Ryoho 2007 Jul;34(7):1034-9

Curr Opin Oncol 2007 May;19(3):216-21

Wolters Kluwer Health Adis, Auckland, New Zealand.

(1) Head and neck squamous cell carcinoma is the sixth most frequently occurring cancer worldwide.(2) Chemotherapy has shown some success as part of multimodal treatment schedules for locally advanced, nonmetastatic head and neck squamous cell carcinoma, and too a much lesser extent for metastatic head and neck squamous cell carcinoma.(3) A recent meta-analysis of 32 studies involving >10,000 patients concluded that chemotherapy added to radiotherapy produces a large survival advantage relative to radiotherapy alone. Read More

Curr Opin Oncol 2007 May;19(3):177-9

Medical Oncology Department, Jules Bordet Institute, Brussels, Belgium.

There have been important advances in the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). For patients with unresectable disease, the use of platinum-based chemoradiotherapy has improved the 3-year survival rate from 15-20% to 35-50%. The results of recent studies involving sequential therapy of induction chemotherapy including taxanes and chemoradiation have shown encouraging survival rates, near to 60-70%. Read More

Nat Clin Pract Oncol 2007 Mar;4(3):172-80

Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, K4/316 Clinical Sciences Center, Madison, WI 53792, USA.

Widening indications for combining radiation therapy with cytotoxic or molecular-targeted drugs have mainly been driven by pragmatic clinical trials. With a flurry of novel drugs in various stages of preclinical and clinical development there is a need to revise the framework that has traditionally been used for discussing possible drug-radiation interactions, especially because many of the new drugs are directed at a specific molecular target. Spatial cooperation, cytotoxic enhancement, biological cooperation, temporal modulation and normal tissue protection are proposed as five primary exploitable mechanisms for the rational combination of drugs with radiation for cancer therapy. Read More

Clin Adv Hematol Oncol 2006 Aug;4(8):611-9

Division of Hematology and Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

In recent years, several therapeutic advances have been made in squamous cell carcinoma of the head and neck (SCCHN). However, despite multimodality therapy, patients with locally advanced SCCHN continue to demonstrate suboptimal 5-year survival rates. The addition of novel, targeted agents to traditional therapies holds promise for clinical benefit. Read More

Med Oncol 2006 ;23(1):1-15

Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.

Over the past decade important advances have been made in the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). Traditionally, chemotherapy has been incorporated in the treatment of SCCHN either before local treatment as induction, concomitantly with radiation, or following local treatment as adjuvant therapy. A number of randomized trials and meta-analyses have demonstrated that induction chemotherapy (usually based on the combination of cisplatin and 5-d continuous infusion of fluorouracil) followed by local treatment or concomitant chemoradiotherapy (CCRT) each prolongs survival and results in organ preservation in a significant number of patients. Read More

Expert Opin Pharmacother 2006 Mar;7(4):489-94

Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, M5G 2M9, Canada.

The Multidisciplinary Symposium on Head and Neck Cancer focused on the emerging data that underlie optimal treatment for head and neck cancers, with a particular focus on squamous cell carcinoma of the head and neck. In-depth discussions showcased the published Phase II and Phase III data on the treatment of locally advanced disease with both induction chemotherapy and concurrent chemoradiotherapy. Molecular targets of interest and relevance in this tumour type were identified, as were the agents which target these putative proteins or pathways of carcinogenesis. Read More