Personalized Medicine Approach for an Exceptional Response to Multiple-recurrent and Metastatic HER2-positive Oropharyngeal Squamous Cell Carcinoma

2017 ◽  
Vol 126 (4) ◽  
pp. 334-339 ◽  
Author(s):  
Nolan B. Seim ◽  
Stephen Y. Kang ◽  
Milan Bhandari ◽  
Riley G. Jones ◽  
Theodoros N. Teknos
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Chemotherapeutic Agent ◽  
Tumor Biology ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Her2 Positive ◽  
Recurrent Squamous Cell Carcinoma ◽  
Unexpected Outcomes

Introduction: Advanced stage squamous cell carcinoma of the head and neck carries an overall poor prognosis, and survivorship gains have remained relatively stagnant compared to other malignancies due to its complex tumor biology and lack of proven effective targeting agents. Methods: We present a case of an exceptional responder to molecular-targeted therapy for metastatic oropharyngeal squamous cell carcinoma using a chemotherapeutic agent FDA approved for breast cancer and targeting the HER2/Neu receptor in order to discuss the larger clinical implications. Results: The National Cancer Institute (NCI) has recently instituted the Exceptional Responders Initiative in order to identify such patients with unexpected outcomes in order to expedite the development of additional targeted therapies. This case illustrates the opportunity for cure using targeted oncogene identification in a scenario of recurrent squamous cell carcinoma with lung metastasis typically considered fatal. Conclusions: Molecular tumor analysis is an infrequently utilized tool in head and neck squamous cell carcinoma; however, as understanding of biologic mechanisms improves, additional molecular targets will become available and expand treatment opportunities such as HER2/Neu targeting. The Exceptional Responders Initiative is a unique strategy with potential to expedite progress.

Specific Targeting of HER2-Positive Head and Neck Squamous Cell Carcinoma Line HN5 by Idarubicin-ZHER2 Affibody Conjugate

2018 ◽  
Vol 19 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Marzieh Ghanemi ◽  
Aminollah Pourshohod ◽  
Mohammad Ali Ghaffari ◽  
Alireza kheirollah ◽  
Mansour Amin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Line ◽  
Squamous Cell ◽  
Optimum Concentration ◽  
Her2 Positive ◽  
Affibody Molecules ◽  
Specific Targeting ◽  
Mcf 7

Background:Expression of human epidermal growth factor receptor type 2 (HER2) in head and neck squamous cell carcinoma (HNSCC) cell line HN5 can be employed with great opportunities of success for specific targeting of anti-cancer chemotherapeutic agents.Objective:In the current study, HER2-specific affibody molecule, ZHER2:342 (an engineered protein with great affinity for HER2 receptors) was selected for conjugation to idarubicin (an anti-neoplastic antibiotic).Method:ZHER2:342 affibody gene with one added cysteine code at the its 5′ end was synthesized de novo and then inserted into pET302 plasmid and transferred to E. Coli BL21 hosting system. After induction of protein expression, the recombinant ZHER2 affibody molecules were purified using Ni- NTA resin and purity was analyzed through SDS-PAGE. Affinity-purified affibody molecules were conjugated to idarubicin through a heterobifunctional crosslinker, sulfosuccinimidyl 4-(Nmaleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC). Specific toxicity of idarubicin-ZHER2 affibody conjugate against two HER2-positive cells, HN5 and MCF-7 was assessed through MTT assay after an exposure time of 48 hours with different concentrations of conjugate.Results:Idarubicin in the non-conjugated form showed potent toxic effects against both cell lines, while HN5 cells were significantly more sensitive compared to MCF-7 cells. Dimeric ZHER2 affibody showed a mild decreasing effect on growth of both HN5 and MCF-7 cells at optimum concentration. Idarubicin-ZHER2 affibody conjugate at an optimum concentration reduced viability of HN5 cell line more efficiently compared to MCF-7 cell line.In conclusion, idarubicin-ZHER2 affibody conjugate in optimum concentrations can be used for specific targeting and killing of HN5 cells.

Association of Cystic Neck Metastases and Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma

2009 ◽  
Vol 133 (11) ◽  
pp. 1798-1803
Author(s):  
Jonathan B. McHugh
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Sexual Behaviors ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Treatment Modalities ◽  
Neck Metastases

Abstract Human papillomavirus is an established cause of oropharyngeal squamous cell carcinoma. Similar to cervical cancer, these cancers are usually caused by high-risk human papillomavirus types 16 and 18 and are associated with high-risk sexual behaviors. Human papillomavirus–associated oropharyngeal squamous cell carcinoma typically affects the palatine and lingual tonsils and frequently results in cystic neck metastases. The histopathology of this subset of head and neck squamous cell carcinoma is unique and typically characterized by poorly differentiated, nonkeratinizing morphology with a basaloid appearance. These tumors occur in younger patients and are more often seen in nonsmokers compared with conventional oral cavity and oropharyngeal squamous cell carcinomas. The incidence of human papillomavirus–associated squamous cell carcinoma is increasing. Recognition of this unique clinicopathologic subset of head and neck carcinoma is important because these patients typically respond more favorably to organ-sparing treatment modalities and have an improved prognosis.

Sequential methotrexate, 5-fluorouracil, and cisplatin in the treatment of recurrent squamous-cell carcinoma of the head and neck: failure of hypertonic saline to reduce the nephrotoxicity of cisplatin.

1986 ◽  
Vol 4 (11) ◽  
pp. 1670-1676 ◽  
Author(s):  
I W Dimery ◽  
S S Legha
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Hypertonic Saline ◽  
Squamous Cell ◽  
Renal Toxicity ◽  
Recurrent Squamous Cell Carcinoma ◽  
Duration Of Response ◽  
Median Cumulative Dose ◽  
To Receive

Fifty patients with histologically proven squamous-cell carcinoma of the head and neck, recurrent after surgery and/or radiation therapy, were treated with a triple-drug combination of methotrexate (MTX), 250 mg/m2 intravenously (IV) on day 1, followed by 5-fluorouracil (5-FU), 600 mg/m2 IV on days 1 and 2, followed by cisplatin, 50 to 60 mg/m2 IV on days 3 and 4. Patients were randomly assigned to receive cisplatin either in 300 mL of 3% saline or with standard mannitol diuresis along with appropriate hydration. The courses of treatment were repeated every 3 to 4 weeks. Among 47 evaluable patients, there were four complete responses (CRs) and 17 partial responses (PRs) (9% and 36%, respectively). The median duration of response was 23 weeks and the overall survival was 7 months. The median survival of responders v nonresponders was 12 months and 6 months, respectively. Nausea and vomiting was experienced by all patients and diarrhea was experienced by 36% of patients. Neutropenia occurred in 37 patients (79%) and resulted in fever or infection in 11 patients (23%) and death in two patients. Mild renal failure (persistent serum creatinine greater than 1.5 mg/ dL) was observed in ten patients (21%), six treated with 3% saline and four treated with mannitol. The median cumulative dose of cisplatin that lead to the development of renal impairment was 485 mg/m2 in the hypertonic saline arm and 550 mg/m2 in the mannitol arm (P = .40). The antitumor activity of this regimen was not superior to that of sequential MTX and 5-FU. The use of hypertonic saline was not effective in reducing the renal toxicity of cisplatin.

Phase II Trial of a Paclitaxel-Carboplatin Combination in Recurrent Squamous Cell Carcinoma of the Head and Neck

Oncology ◽  
2000 ◽  
Vol 60 (1) ◽  
pp. 66-71 ◽  
Author(s):  
X. Pivot ◽  
L. Cals ◽  
D. Cupissol ◽  
E. Guardiola ◽  
X. Tchiknavorian ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Phase Ii ◽  
Squamous Cell ◽  
Phase Ii Trial ◽  
Recurrent Squamous Cell Carcinoma
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