Molecularly targeted cancer therapy: some lessons from the past decade

Huang, Min; Shen, Aijun; Ding, Jian; Geng, Meiyu

doi:10.1016/j.tips.2013.11.004

Cited by 251 publications

(190 citation statements)

References 91 publications

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“…For advanced stage disease, current surgical and chemoradiotherapeutic treatment regimens are frequently ineffective and often cause severe side effects (3). In addition, the use of targeted therapies for treating advanced HNSCC is limited to the EGFR inhibitor cetuximab (4). The high mortality rate of advanced HNSCC and varying therapeutic success highlight the need for novel therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Koole

Brunen

Kempen

et al. 2016

Clinical Cancer Research

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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. In this study, we have investigated the prognostic value of FGFR1 expression in HNSCC, the therapeutic relevance of targeting FGFR with AZD4547, and potential resistant mechanisms.Experimental Design: IHC and FISH were applied on tissue microarrays to investigate FGFR1 protein expression and FGFR1 gene copy numbers in 452 HNSCCs. The sensitivity of HNSCC cell lines to AZD4547, either as single or combination treatment with the EGFR inhibitor gefitinib, was assessed using long-term colony formation assays, short-term viability assays, and biochemical analysis.Results: FGFR1 protein overexpression occurred in 82% (36/ 44) of human papillomavirus (HPV)-positive HNSCC and 75% (294/392) of HPV-negative HNSCC and relates with poor overall survival and disease-free survival in HPV-negative HNSCC [HR, 3.07; 95% confidence interval (CI), 1.74-6.90; P ¼ 0.001 and HR, 1.53; 95% CI, 1.04-2.39; P ¼ 0.033]. Moreover, the FGFR1 gene was amplified in 3% (3/110) of HPV-negative HNSCC. Treatment of the high FGFR1-expressing cell line CCL30 with AZD4547 reduced cell proliferation and FGFR signaling. Two FGFR-amplified cell lines, SCC147 and BICR16, were resistant to AZD4547 treatment due to EGFR signaling. Combined AZD4547 and gefitinib treatment synergistically inhibited the proliferation of resistant cell lines.Conclusions: Here, we identify high FGFR1 expression as a candidate prognostic biomarker in HPV-negative HNSCC. Furthermore, we provide a rationale for treating FGFR1-expressing HNSCC with the FGFR inhibitor AZD4547 and for combining AZD4547 and gefitinib in FGFR inhibitor-resistant HNSCC patients. Clin Cancer Res; 22(15); 3884-93. Ó2016 AACR.

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Section: Introductionmentioning

confidence: 99%

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Koole

Brunen

Kempen

et al. 2016

Clinical Cancer Research

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“…A promising alternative is the use of molecular targeted strategies to disrupt mitosis without interfering with microtubule dynamics. As the targeted proteins only intervene in actively dividing cells, these strategies would not affect nondividing cells thereby decreasing the treatment-related adverse effects [7].…”

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confidence: 99%

Biodistribution and pharmacokinetics of Mad2 siRNA-loaded EGFR-targeted chitosan nanoparticles in cisplatin sensitive and resistant lung cancer models

et al. 2016

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Background: The present study focuses on biodistribution profile and pharmacokinetic parameters of EGFR-targeted chitosan nanoparticles (TG CS nanoparticles) for siRNA/cisplatin combination therapy of lung cancer. Material & methods: Mad2 siRNA was encapsulated in EGFR targeted and nontargeted (NTG) CS nanoparticles by electrostatic interaction. The biodistribution of the nanoparticles was assessed qualitatively and quantitatively in cisplatin (DDP) sensitive and resistant lung cancer xenograft model. Results: TG nanoparticles showed a consistent and preferential tumor targeting ability with rapid clearance from the plasma to infiltrate and sustain within the tumor up to 96 h. They exhibit a sixfold higher tumor targeting efficiency compared with the NTG nanoparticles. Conclusion: TG nanoparticles present as an attractive drug delivery platform for RNAi therapeutics against NSCLC.

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“…Remarkable advances in understanding the molecular mechanisms of cancer progression have made it possible to design molecularly targeted drugs for cancer therapy (Huang et al 2014). Traditional chemotherapy attacks rapidly dividing cells and thus side effects are inevitable, whereas molecularly targeted therapy focuses on molecular abnormalities specific to cancer and so is less harmful to normal cells.…”

Section: Molecularly Targeted Cancer Therapymentioning

confidence: 99%

“…Traditional chemotherapy attacks rapidly dividing cells and thus side effects are inevitable, whereas molecularly targeted therapy focuses on molecular abnormalities specific to cancer and so is less harmful to normal cells. Over 30 molecularly targeted anti-cancer drugs have been approved for clinical use [see Table 5, (Huang et al 2014)]. Molecularly targeted cancer drugs target growth factor receptors such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), signaling molecules such as RAS and mTOR, inhibitor of apoptosis proteins, angiogenesis regulators such as vascular endothelial growth factor receptor (VEGFR), and immune checkpoint proteins such as programmed death ligand 1 (PD-L1).…”

Section: Molecularly Targeted Cancer Therapymentioning

confidence: 99%

State of the art in medical applications using non-thermal atmospheric pressure plasma

Tanaka

Ishikawa

Mizuno

et al. 2017

Rev. Mod. Plasma Phys.

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Plasma medical science is a novel interdisciplinary field that combines studies on plasma science and medical science, with the anticipation that understanding the scientific principles governing plasma medical science will lead to innovations in the field. Non-thermal atmospheric pressure plasma has been used for medical treatments, such as for cancer, blood coagulation, and wound healing. The interactions that occur between plasma and cells/tissues have been analyzed extensively. Direct and indirect treatment of cells with plasma has broadened the applications of non-thermal atmospheric pressure plasma in medicine. Examples of indirect treatment include plasma-assisted immune-therapy and plasma-activated medium. Controlling intracellular redox balance may be key in plasma cancer treatment. Animal studies are required to test the effectiveness and safety of these treatments for future clinical applications.Keywords Plasma medical science Á Plasma cancer therapy Á Plasma-activated medium (PAM) Á Reactive oxygen species (ROS) Abbreviations ALKAnaplastic lymphoma kinase AMD Age-related macular degeneration APF Aminophenyl Fluorescein CNV

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Molecularly targeted cancer therapy: some lessons from the past decade

Cited by 251 publications

References 91 publications

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Biodistribution and pharmacokinetics of Mad2 siRNA-loaded EGFR-targeted chitosan nanoparticles in cisplatin sensitive and resistant lung cancer models

State of the art in medical applications using non-thermal atmospheric pressure plasma

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