From molecular diagnostics to molecular targeted therapy with natural product small molecule inhibitors in oral squamous cell carcinoma

Abstract A better understanding of cancer biology has led to the development of molecular targeted therapy, which has dramatically improved the outcome of some cancer patients, especially when a biomarker of efficacy has been used for patients’ selection. In head and neck oncology, cetuximab that targets epidermal growth factor receptor is the only targeted therapy that demonstrated a survival benefit, both in the recurrent and in the locally advanced settings, yet without prior patients’ selection. We herein review the clinical development of targeted therapy in head and neck squamous cell carcinoma in light of the molecular landscape and give insights in on how innovative clinical trial designs may speed up biomarker discovery and deployment of new molecular targeted therapies. Given the recent approval of immune checkpoint inhibitors targeting programmed cell death-1 in head and neck squamous cell carcinoma, it remains to be determined how targeted therapy will be incorporated into a global drug development strategy that will inevitably incorporate immunotherapy.

Download Full-text

JQ1, a small molecule inhibitor of BRD4, suppresses cell growth and invasion in oral squamous cell carcinoma

Oncology Reports ◽

10.3892/or.2016.5037 ◽

2016 ◽

Vol 36 (4) ◽

pp. 1989-1996 ◽

Cited By ~ 25

Author(s):

Limei Wang ◽

Xiuyin Wu ◽

Ping Huang ◽

Zhijun Lv ◽

Yuping Qi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Growth ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Small Molecule ◽

Squamous Cell ◽

Small Molecule Inhibitor ◽

Molecule Inhibitor

Download Full-text

Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells

Cellular Physiology and Biochemistry ◽

10.1159/000445594 ◽

2016 ◽

Vol 38 (6) ◽

pp. 2426-2437 ◽

Cited By ~ 9

Author(s):

Wei Zhang ◽

Yuan Liu ◽

Yu Feng Li ◽

Yun Yue ◽

Xinghua Yang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Growth ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Small Molecule ◽

Squamous Cell ◽

Migration And Invasion ◽

Dependent Manner ◽

Gene And Protein Expression

Background/Aims: Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first “Survivin suppressant” but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. Survivin protein plays critical roles in oral squamous cell carcinoma (OSCC), suggesting that YM155 would be extremely valuable for OSCC. In this study, we tested our hypothesis whether YM155 could be an effective inhibitor of cell growth, invasion and angiogenesis in oral squamous cell carcinoma (OSCC) cells. Methods: SCC9 and SCC25 were treated with different concentration of YM155 for indicated time. Using MTT assay and flow cytometry analysis to detect cell growth and apoptosis; Using transwell and Wound healing assay to detect migration and invasion; Using reverse transcription-PCR, Western blotting and electrophoretic mobility shift assay for measuring gene and protein expression, and DNA binding activity of NF-κB. Results: YM155 inhibited survivin-rich expressed SCC9 cell growth in a dose- and time dependent manner. This was accompanied by increased apoptosis and concomitant attenuation of NF-κB and downregulation of NF-κB downstream genes MMP-9, resulting in the inhibition of SCC9 cell migration and invasion in vitro and caused antitumor activity and anti metastasis in vivo. YM155 treatment did not affect cell growth, apoptosis and invasion of surviving-poor expressed SCC25 cells in vitro. Conclusions: YM155 is a potent inhibitor of progression of SCC9 cells, which could be due to attenuation of survivin signaling processes. Our findings provide evidence showing that YM155 could act as a small molecule survivin inhibitor on survivin-rich expressed SCC9 cells in culture as well as when grown as tumor in a xenograft model. We also suggest that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed OSCC.

Download Full-text

Current Trends and Future Prospects of Molecular Targeted Therapy in Head and Neck Squamous Cell Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms22010240 ◽

2020 ◽

Vol 22 (1) ◽

pp. 240

Author(s):

Naoya Kitamura ◽

Shinya Sento ◽

Yasumasa Yoshizawa ◽

Eri Sasabe ◽

Yasusei Kudo ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Targeted Therapy ◽

Drug Therapy ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Molecular Targeted Therapy ◽

Future Prospects ◽

Current Trends ◽

Anti Cancer

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. Therefore, we summarize clinical trials of molecular targeted therapy and biomarkers in HNSCC from previous studies. Here we show the current trends and future prospects of molecular targeted therapy in HNSCC.

Download Full-text

Progress of molecular targeted therapy for head and neck cancer in clinical aspects

Molecular Biomedicine ◽

10.1186/s43556-021-00032-5 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Kenji Nakano

Keyword(s):

Squamous Cell Carcinoma ◽

Clinical Trials ◽

Head And Neck Cancer ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Squamous Cell ◽

Molecular Targeted Therapy

AbstractSince the body’s head and neck area affects many functions such as breathing, swallowing, and speaking, systemic treatments to head and neck cancer patients are important not only for survival but also for preserving functions and quality of life. With the progress that has been made in molecular targeted therapy, anti-EGFR antibody (cetuximab) and immune checkpoint inhibitors (nivolumab, pembrolizumab) have provided survival benefits to head and neck cancer patients and are approved for clinical practice. Clinical trials incorporating these new drugs for patients with locally advanced head/neck cancers are underway. However, the existing clinical evidence regarding molecular targeted drugs for head and neck cancers is based mostly on clinical trials allocated to squamous cell carcinoma patients. New targeted therapies for non-squamous cell carcinoma patients were recently reported, e.g., tyrosine kinase inhibitors for the treatment of thyroid cancers and HER2-targeted therapy for salivary gland cancers. With the goal of improving local control, molecular targeted treatment strategies as salvage local therapy are being investigated, including boron neutron capture therapy (BNCT) and near-infrared photoimmunotherapy (NIR-PIT). Herein the history and landscape of molecular targeted therapy for head and neck cancers are summarized and reviewed.

Download Full-text