Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic myelogenous leukemia (CML) is an example of a "well-differentiated" neoplasm that develops following neoplastic transformation of a precursor cell. The biology of astrocytic neoplasms can be interpreted in light of concepts that have emerged from studies of the myeloproliferative disorders. Astrocytomas may arise from a pluripotential precursor cell whose progeny, although transformed, retain the ability to differentiate, and do so along astrocytic lines. The result is a neoplasm composed of "mature" tumor cells, similar one to another, and resembling normal astrocytes. Malignant change, like blast crisis in CML, then occurs as a consequence of further molecular genetic events leading to accelerated growth and maturation arrest in a previously differentiating neoplastic cell. This hypothesis challenges the conventional view that astrocytomas arise from astrocytes and that malignant change occurs as a result of dedifferentiation. Extensions of this hypothesis may be relevant to the biology of other glial tumors.
 ...
PMID:The biology of astrocytoma: lessons learned from chronic myelogenous leukemia--hypothesis. 347 24

Tyrosine kinases are enzymes that regulate mitosis, differentiation, migration, neovascularization, and apoptosis. Their spectrum and association with specific malignancies offer multiple targets for therapeutic intervention. Chronic myelogenous leukemia (CML) represents an ideal target for a therapy using a selective inhibitor of the BCR-ABL tyrosine kinase. The 2-phenylpyrimidine derivative STI571 was rationally designed to inhibit ABL and BCR-ABL tyrosine kinase activities through competitive ATP-binding pocket interactions. Phase II data demonstrate hematologic and cytogenetic responses in interferon refractory chronic-phase, accelerated-phase and blast crisis patients. However, long-term observation is needed to confirm that response data result in prolongation of survival. STI571 is being studied in other malignancies, including leukemias characterized by expression of alternate molecular forms of BCR-ABL and those expressing protein tyrosine kinases with ATP-binding pockets structurally similar to ABL, e.g. c-kit and PDGF-R. Gastrointestinal stromal tumor (GIST) cells overexpress the stem cell factor receptor CD117, the product of the proto-oncogene c-kit. Inhibition of c-kit in vivo results in an immediate metabolic change of the tumor cells, detectable by positron emission tomography. Since c-kit overexpression is inhibited in small-cell lung cancer cell lines, a study with STI571 as second-line therapy of c-kit-positive small-cell lung cancer is in progress. Clinical studies are ongoing in malignancies associated with an enhanced activity of the PDGF-R, such as highgrade glioma, prostate cancer and leukemias with rearrangements of PDGF-R. The development of selective tyrosine kinase inhibitors is considered a promising approach for the design of new drugs. Clinical responses to STI571 in various malignancies may stimulate greater interest in the clinical use of tyrosine kinase inhibitors.
 ...
PMID:[Selective inhibition of tyrosine kinases - a new therapeutic principle in oncology]. 1160 Aug 16