Biomarkers, Tumor ; genetics ; metabolism ; Humans ; Molecular Targeted Therapy ; standards ; Mutation ; Neoplasms ; drug therapy ; genetics ; metabolism ; pathology

Antineoplastic Agents ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; genetics ; metabolism ; Genes, ras ; genetics ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Molecular Targeted Therapy ; methods ; Mutation ; Neoplasms ; drug therapy ; genetics ; metabolism ; Pancreatic Neoplasms ; drug therapy ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; metabolism ; Proto-Oncogene Proteins p21(ras) ; Receptor, Epidermal Growth Factor ; drug effects ; metabolism ; Signal Transduction ; ras Proteins ; genetics ; metabolism

Squamous cell lung cancer (SqCLC) is a unique clinical and histologic category of non-small cell lung cancer (NSCLC). Most of patients with SqCLC tend to be older, typically at advanced stage, associated with smoking and have more complications. With progress of targeted therapy of lung cancer, we identified several potential actionable genetic abnormalities such as FGFR. Several FGFR inhibitors have been approved for clinical use in different cancers. And some of these agents are currently under investigation in clinical trials for SqCLC. This article summarizes the current knowledge about FGFR aberrations, the relative inhibitors in development and clinical data in SqCLC.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Molecular Targeted Therapy ; methods ; Mutation ; Receptors, Fibroblast Growth Factor ; genetics ; metabolism

Personalising cancer treatment to optimise therapeutic efficacy while minimising exposure to the toxicities of ineffective drugs is the holy grail of medical oncology. Clinical parameters and conventional histopathological characterisations of cancers are no longer adequate to guide the practising oncologists in treatment planning. The explosion of knowledge in cancer molecular biology has led to the availability of tumour-specific molecules that serve as predictive and prognostic markers. In breast cancer, HER-2 positivity is a good predictor for success of anti-HER-2 trastuzumab monoclonal antibody therapy. K-ras mutational status predicts the likelihood of response to anti-EGFR monoclonal antibodies in advanced colorectal cancers. Similarly, EGFR mutational status in pulmonary adenocarcinoma is highly predictive for responses or otherwise to tyrosine kinase inhibitors. Notwithstanding our deeper understanding of tumour biology and the availability of predictive and prognostic laboratory tools, we are still far from achieving our dream of the perfect personalised cancer treatment, as each tumour in a particular patient is unique to itself. A much coveted, real-time, anti-tumour drug sensitivity testing in the future may one day pave the way for truly treating the right tumour with the right drug in the right patient.
Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; genetics ; Genomics ; methods ; Humans ; Neoplasms ; drug therapy ; genetics ; metabolism ; Prognosis

Phosphatide acid (PA) is a kind of multifunctional bioactive phospholipid. It has been proved that PA produced by lysophosphatide acid acyltransferase (LPAATbeta) was involved in several signalling pathways in tumor cells, leading to the proliferation, apoptosis, migration, invasion, respiratory burst, expression and release of cytokine form tumor cells. The fact that expression of LPAATbeta was higher in tumor tissues than in their homologous normal tissues, and that antitumor effect of inhibitng LPAATbeta on solid tumor and hematological malignancy suggested that the targeting LPAATbeta would be a promising method of antitumor treatment. In this paper, the relevant basic and preclinical researches of LPAATbeta on antitumor treatment were summarized.
Acyltransferases ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Neoplasms ; drug therapy ; enzymology ; Phosphatidic Acids ; metabolism ; physiology

OBJECTIVE: To analyze the impact of β-tubulin-III (TUBB3), thymidylate synthase (TS) and excision repair cross complementation group 1 (ERCC1) mRNA expression on chemoresponse and clinical outcome of patients with advanced gastric cancer treated with TXT/CDDP/FU (DCF) regimen chemotherapy. METHODS: The study population consisted of 48 patients with advanced gastric cancer. All patients were treated with DCF regimen palliative chemotherapy. The mRNA expressions of TUBB3, TS and ERCC1 of primary tumors were examined by multiplex branched-DNA liquid chip technology. RESULTS: The patients with low TUBB3 mRNA expression had higher response rate to chemotherapy than patients with high TUBB3 expression (P=0.011). There were no significant differences between response rate and TS or ERCC1 expression pattern. Median overall survival (OS) and median time to progression (TTP) were significantly longer in patients with low TUBB3 mRNA expression (P=0.002, P<0.001). TS or ERCC1 expression was not correlated with TTP and OS. In the combined analysis including TUBB3, TS and ERCC1, the patients with 0 or 1 high expression gene had better response rate, TTP and OS than the remaining patients (all P<0.001). Multivariate analysis revealed that ECOG (Eastern Cooperative Oncology Group)≥2 (HR=2.42, P=0.009) and TUBB3 (HR=2.34, P=0.036) mRNA expression significantly impacted on OS. CONCLUSION High TUBB3 mRNA expression is correlated with resistance to DCF regimen chemotherapy. TUBB3 might be a predictive and prognostic factor in patients with advanced gastric cancer treated with TXT-based chemotherapy. The combined evaluation of TUBB3, TS and ERCC1 expression can promote the individual treatment in advanced gastric cancer.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Drug Resistance, Neoplasm ; Endonucleases ; genetics ; metabolism ; Humans ; RNA, Messenger ; genetics ; metabolism ; Stomach Neoplasms ; drug therapy ; genetics ; Thymidylate Synthase ; genetics ; metabolism ; Treatment Outcome ; Tubulin ; genetics ; metabolism

Carcinoma ; drug therapy ; genetics ; metabolism ; pathology ; radiotherapy ; Desmoplastic Small Round Cell Tumor ; metabolism ; pathology ; Diagnosis, Differential ; Gene Rearrangement ; Head and Neck Neoplasms ; drug therapy ; genetics ; metabolism ; radiotherapy ; Humans ; Keratin-20 ; metabolism ; Keratin-7 ; metabolism ; Lymphatic Metastasis ; Male ; Mediastinal Neoplasms ; drug therapy ; genetics ; metabolism ; radiotherapy ; Melanoma ; metabolism ; pathology ; Neuroectodermal Tumors, Primitive ; metabolism ; pathology ; Nuclear Proteins ; genetics ; metabolism ; Oncogene Proteins ; genetics ; metabolism ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Rhabdomyosarcoma ; metabolism ; pathology ; Thymus Neoplasms ; drug therapy ; genetics ; metabolism ; radiotherapy

Hedgehog was first described in Drosophila melanogaster by the Nobel laureates Eric Wieschaus and Christiane Nüsslein-Volhard. The hedgehog (Hh) pathway is a major regulator of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of a rare familial disease, Gorlin syndrome, in 1996. Follow-up studies revealed activation of this pathway in basal cell carcinoma, medulloblastoma and, leukemia as well as in gastrointestinal, lung, ovarian, breast, and prostate cancer. Targeted inhibition of Hh signaling is now believed to be effective in the treatment and prevention of human cancer. The discovery and synthesis of specific inhibitors for this pathway are even more exciting. In this review, we summarize major advances in the understanding of Hh signaling pathway activation in human cancer, mouse models for studying Hh-mediated carcinogenesis, the roles of Hh signaling in tumor development and metastasis, antagonists for Hh signaling and their clinical implications.
Animals ; Antineoplastic Agents ; therapeutic use ; Basal Cell Nevus Syndrome ; drug therapy ; metabolism ; Carcinoma, Basal Cell ; drug therapy ; metabolism ; Cell Differentiation ; Cerebellar Neoplasms ; drug therapy ; metabolism ; Hedgehog Proteins ; antagonists & inhibitors ; metabolism ; Humans ; Medulloblastoma ; drug therapy ; metabolism ; Models, Animal ; Neoplasms ; drug therapy ; metabolism ; Patched Receptors ; Receptors, Cell Surface ; genetics ; metabolism ; Signal Transduction ; drug effects ; Skin Neoplasms ; drug therapy ; metabolism

MicroRNAs (miRNAs) are endogenous noncoding RNAs, about 22 nucleotides in length, that mediate post-transcriptional gene modulation by annealing to inexactly complementary sequences in the 3'-untranslated regions of target mRNAs. miRNA alterations are involved in the initiation and progression of human diseases. miRNA-expression profiling of human diseases has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. Recent evidence has suggested miRNAs as viable therapeutic targets for a wide range of human diseases. Several approaches were performed, the experimental examination of these techniques and the resultant findings not only indicate feasibility of interfering miRNA action in a gene-specific fashion but also may provide a new research tool for studying function of miRNAs. The new approaches also have the potential of becoming alternative gene therapy strategies.
Animals ; Drug Design ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Silencing ; Genetic Therapy ; methods ; Heart Diseases ; genetics ; metabolism ; therapy ; Humans ; Hypertension ; genetics ; metabolism ; therapy ; MicroRNAs ; genetics ; metabolism ; Neoplasms ; genetics ; metabolism ; therapy ; RNA, Messenger ; genetics

Animals ; Antifungal Agents ; chemistry ; pharmacology ; Drug Repositioning ; Hedgehog Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Neoplasms ; drug therapy ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Signal Transduction ; drug effects