Humans ; Histiocytosis ; Receptor Protein-Tyrosine Kinases

Humans ; Lymphoma, Large-Cell, Anaplastic ; Receptor Protein-Tyrosine Kinases

Over the past decade, several kinase inhibitors have been approved based on their clinical benefit in cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. To date, several major mechanisms of acquired resistance, such as secondary mutation of the epidermal growth factor receptor (EGFR) gene, amplification of the MET gene and overexpression of hepatocyte growth factor, have been reported. This review describes the recent findings on the mechanisms of primary and acquired resistance to EGFR tyrosine kinase inhibitors and acquired resistance to anaplastic lymphoma kinase inhibitors, primarily focusing on non-small cell lung carcinoma.
Drug Resistance* ; Epidermal Growth Factor* ; Hepatocyte Growth Factor ; Humans ; Lung ; Lymphoma* ; Phosphotransferases* ; Protein Kinase Inhibitors ; Protein-Tyrosine Kinases ; Receptor Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor*

BACKGROUND: Tyrosine kinase receptor (TKR) is an important protein for normal-development, growth and tumorigenesis in human tissues. The purpose of this study was to evaluate the effect of TKR in the progression of breast cancer. METHODS: The expressions of EphA2, c-met and c-erbB-2 were examined, by using immunohistochemical methods and RT-PCR, in samples of breast tissue that included 111 samples of normal epithelium, 34 samples of ductal carcinoma in situ (DCIS), and 109 samples of invasive ductal carcinomas (IDC). The results were compared with the prognostic parameters of breast cancer including the tumor grade, growth pattern, lymph node metastasis and the expressions of ER, PR, p53 and Ki-67. RESULTS: The protein expressions of the three TKRs were higher in DCIS and IDC than in normal epithelium. The protein expression of EphA2 was correlated with a tumor grade, a labeling index of Ki-67, and the protein expression of c-met. Overexpression of c-erbB-2 was correlated with lymph node metastasis. The mRNA levels of the three TKRs were correlated with each other in normal tissue and IDC. The level of c-met mRNA was higher in the low grade tumors. CONCLUSIONS: The three TKRs may play roles in the tumorigenesis of human breast cancer. The overexpressions of EphA2 and c-erbB-2 may be a poor prognostic parameter in breast cancers.
Breast Neoplasms ; Breast* ; Carcinogenesis ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Epithelium ; Humans* ; Lymph Nodes ; Neoplasm Metastasis ; Protein-Tyrosine Kinases* ; Receptor Protein-Tyrosine Kinases* ; RNA, Messenger ; Tyrosine*

The emergence of new therapeutic agents for non-small cell lung cancer (NSCLC) implies that histologic subtyping and molecular predictive testing are now essential for therapeutic decisions. Histologic subtype predicts the efficacy and toxicity of some treatment agents, as do genetic alterations, which can be important predictive factors in treatment selection. Molecular markers, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement, are the best predictors of response to specific tyrosine kinase inhibitor treatment agents. As the majority of patients with NSCLC present with unresectable disease, it is therefore crucial to optimize the use of tissue samples for diagnostic and predictive examinations, particularly for small biopsy and cytology specimens. Therefore, each institution needs to develop a diagnostic approach requiring close communication between the pulmonologist, radiologist, pathologist, and oncologist in order to preserve sufficient biopsy materials for molecular analysis as well as to ensure rapid diagnosis. Currently, personalized medicine in NSCLC is based on the histologic subtype and molecular status. This review summarizes strategies for tissue acquisition, histologic subtyping and molecular analysis for predictive testing in NSCLC.
Biopsy* ; Carcinoma, Non-Small-Cell Lung* ; Diagnosis ; Humans ; Precision Medicine ; Lymphoma ; Phosphotransferases ; Protein-Tyrosine Kinases ; Receptor Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor

BACKGROUND: The aim of this study was to determine the cytologic features of anaplastic lymphoma kinase (ALK) expressing pulmonary adenocarcinoma. METHODS: We analyzed the cytopathological findings of 15 cases of endobronchial ultrasound guided aspiration and a case of bronchial washing. These cases were selected based on the histomorphology of ALK-rearranged lung adenocarcinoma. RESULTS: Cytology showed mucinous (81.3%) and hemorrhagic (50%) backgrounds. The cells were arranged in tubulopapillary or tubulocribriform patterns (93.8%), and clusters (56.3%) admixed with signet ring cell features (87.5%). The tumor cells were monotonous and uniform with vesicular nuclei and a small nucleolus. CONCLUSIONS: The characteristic findings were sheets showing a tubulopapillary or tubulocribriform appearance, with vesicular nuclei and a bland chromatin pattern (p<0.001). Scattered signet ring cells were helpful in suggesting ALK-positive adenocarcinoma (p<0.001).
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung ; Chromatin ; Lung ; Lymphoma ; Mucins ; Phosphotransferases ; Receptor Protein-Tyrosine Kinases

Humans ; Lymphoma, Large-Cell, Anaplastic ; diagnosis ; enzymology ; therapy ; Receptor Protein-Tyrosine Kinases

ZD1839 (Iressa(R)) is a new anticancer agent, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that blocks signal transduction pathway implicated in the proliferation and survival of cancer cells and other host-dependent process promoting cancer growth. But this agent can induce cutaneous side effects including acneiform eruption, dry skin, and hair abnormality, which is related with the interruption of normal epidermal and hair follicular kinetics. We report a case of hair change and acneiform eruption induced by ZD1839 (Iressa(R)).
Acneiform Eruptions* ; Hair* ; Kinetics ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Signal Transduction ; Skin

Adult ; Humans ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; Male ; Receptor Protein-Tyrosine Kinases ; metabolism

receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors, new therapeutic strategies are needed to improve clinical outcomes. Immunotherapy through the use of immune checkpoint inhibitors has provided one of the most important breakthroughs in the management of solid tumors, including lung cancers, and has shown promising results in numerous clinical trials. This review will present the current status of immunotherapy for lung cancer and future perspectives on these treatments.]]>
Immunotherapy ; Lung Neoplasms ; Lung ; Lymphoma ; Phosphotransferases ; Prognosis ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor