Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixty years ago, 6-thioguanine (6-TG) was introduced into the clinic. We suggest its full potential in therapy may not have been reached. In this paper, we contrast 6-TG and the more widely used 6-mercaptopurine; discuss 6-TG metabolism, pharmacokinetics, dosage and schedule; and summarize many of the early studies that have shown infrequent but nevertheless positive results with 6-TG treatment of cancers. We also consider studies that suggest that combinations of 6-TG with other agents may enhance antitumor effects. Although not yet tested in man, 6-TG has recently been proposed to treat a wide variety of cancers with a high frequency of homozygous deletion of the gene for methylthioadenosine phosphorylase (MTAP), often codeleted with the adjacent tumor suppressor CDKN2A (p16). Among the cancers with a high frequency of MTAP deficiency are leukemias, lymphomas, mesothelioma, melanoma, biliary tract cancer, glioblastoma, osteosarcoma, soft tissue sarcoma, neuroendocrine tumors, and lung, pancreatic, and squamous cell carcinomas. The method involves pretreatment with the naturally occurring nucleoside methylthioadenosine (MTA), the substrate for the enzyme MTAP. MTA pretreatment protects normal host tissues, but not MTAP-deficient cancers, from 6-TG toxicity and permits administration of doses of 6-TG that are much higher than can now be safely administered. The combination of MTA/6-TG has produced substantial shrinkage or slowing of growth in two different xenograft human tumor models: lymphoblastic leukemia and metastatic prostate carcinoma with neuroendocrine features. Further development and a clinical trial of the proposed MTA/6-TG treatment of MTAP-deficient cancers seem warranted.
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PMID:6-thioguanine: a drug with unrealized potential for cancer therapy. 2492 12

Septin 2 (SEPT2) is a tumor-related gene belonging to the SEPT family that affects the cellular processes of hepatoma carcinoma cells, glioblastoma cells and mesangial cells and is highly expressed in breast cancer, biliary tract cancer and acute myeloid leukemia. Colorectal cancer (CRC) is the third most common type of malignancy in humans. In the present study, Oncomine database was used to compare the expression pattern of SEPT2 mRNA between CRC and normal tissues. Additionally, protein expression in 90 pairs of CRC and paracancerous tissues was analyzed by western blotting and immunohistochemistry (IHC). The results showed that SEPT2 was highly expressed in CRC tissues at the mRNA and protein levels. SEPT2 expression quantified by IHC was associated with lymph node metastasis, the degree of differentiation and TNM staging. Increased SEPT2 wass associated with reduced overall survival (OS) according to Kaplan-Meier analysis. COX proportional hazard analysis indicated that SEPT2 was an independent factor that influenced the OS of patients with CRC. Therefore, SEPT2 was associated with the occurrence, progression and prognosis of CRC and thus, may be a marker and prognostic indicator of CRC.
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PMID:Expression of septin 2 and association with clinicopathological parameters in colorectal cancer. 3140 40

Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved for the treatment of refractory metastatic colorectal cancer (mCRC), advanced gastrointestinal stromal tumors (GIST) previously treated with imatinib and sunitinib, and unresectable hepatocellular carcinoma (HCC) following progression on sorafenib. Regorafenib was initially approved for mCRC based on improved overall survival (OS) in the randomized, placebo-controlled, phase 3 CORRECT trial, which was confirmed in an expanded population of Asian patients in the randomized, placebo-controlled phase 3 CONCUR trial. Approvals in GIST, and more recently in HCC, were based on the results from the randomized, placebo-controlled, phase 3 GRID and RESORCE trials, respectively. In this review, we provide a comprehensive summary of the clinical evidence for approval of regorafenib in mCRC, GIST, and HCC, present emerging evidence of regorafenib activity in other tumor types (namely, gastroesophageal cancer, sarcomas, biliary tract cancer, and glioblastoma), and discuss trials in progress within the context of regorafenib's mechanism of action. We describe recent advances and key lessons learned with regorafenib, including the importance of managing common drug-related toxicities using dose-optimization strategies, the search for biomarkers to predict response to treatment, and highlight some of the unaddressed questions and future directions for regorafenib across tumors.
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PMID:Evolving role of regorafenib for the treatment of advanced cancers. 3219 97