Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Virtually all patients with advanced non-small-cell lung cancer (NSCLC) relapse. Docetaxel has an established, Food and Drug Administration-approved role as salvage therapy in previously treated, platinum-exposed patients. However, the response rate in phase III studies is < 15%, and median survival is only 6-8 months. Temozolomide, a novel triazene derivative with activity in melanoma and anaplastic astrocytoma, has demonstrated activity in C26 adenocarcinoma, Lewis lung cancer, and in phase I studies. A phase II trial was mounted using a unique schedule of oral temozolomide 75 mg/m2 daily for 6 weeks every 8-10 weeks, in patients with previously treated, advanced, incurable NSCLC. Eligibility stipulated an Eastern Cooperative Oncology Group performance status (PS) of 0-2, adequate end organ function, up to 1 prior chemotherapy for advanced (relapsed or metastatic) disease, and up to 1 prior regimen in the context of radiosensitization, adjuvant therapy, or induction. From March 2000 through January 2002, 47 patients (24 male, 23 female) were enrolled. The median age was 67 years. Sixteen patients had a PS of 2, 22 had a PS of 1, and 9 had a PS of 0. It was too early to evaluate 9 patients. Toxicity, with the exception of mild nausea and thrombocytopenia, was negligible. Three patients had a delayed recovery of platelets prompting discontinuation of treatment. Of the 38 evaluable patients, 1 patient had a complete response, 2 patients had a partial response, 12 had stable disease, and 19 had disease progression. Four patients were not evaluable. Six patients died within 30 days of taking temozolomide; 5 of these deaths were not related to treatment upon review by an independent data safety monitoring committee. Temozolomide, using a unique 6-week continuous schedule, has demonstrated activity in the salvage therapy of advanced NSCLC. Toxicity is modest, and accrual to this study continues.
Clin Lung Cancer 2002 May
PMID:Temozolomide in non-small-cell lung cancer: preliminary results of a phase II trial in previously treated patients. 1466 33

Thymic neuroendocrine tumours (TNETs) are uncommon but malignant neoplasms, usually associated with a poor prognosis. The number of cases reported is limited to a few hundreds and there are few prognostic factors available. All 28 patients (22 male, 6 female; median age 46.5 years) with thymic neuroendocrine tumour, treated at the Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden between 1985 and 2011 were studied. The overall 3, 5 and 10-year survival was 89%, 79% and 41% respectively. Ki67<10% (p=0.018) as well as surgical resection (p=0.001) and macroscopically radical primary surgery (p=0.034) was associated with increased survival. Staging & grading according to Masaoka and ENETS systems did not correlate with survival. However, a modified ENETS grading showed a positive correlation (p=0.015). Median time to progression was 20.5 months with Temozolomide and 18 months with platinum based therapy. Partial responses were noted in three patients (38%) treated with platinum based therapy and in two patients (20%) treated with Temozolomide based therapy. High proliferative rate, measured by Ki67 index, and absence of macroscopically radical primary resection as well as no surgical resection are three negative prognostic factors in patients with TNETs. Temozolomide or Platinum based chemotherapy should be considered as first-line medical therapy in patients with metastatic or non-resectable tumours.
Lung Cancer 2013 Mar
PMID:Treatment, prognostic markers and survival in thymic neuroendocrine tumours. a study from a single tertiary referral centre. 2328 64

Responses of patients with gliomas to temozolomide are determined by O(6)-methylguanine-DNA methyltransferase (MGMT) and mismatch repair (MMR) pathways. This phase II study (NCT00423150) investigated whether MGMT promoter methylation predicts response in patients with advanced aerodigestive tract and colorectal cancers (CRC). Tumor and serum samples were screened for MGMT promoter methylation. In methylation-positive patients, 150 mg/m(2) temozolomide was administered daily on a seven-day-on, seven-day-off schedule for each 28-day cycle. The primary efficacy endpoint was response rate (RR). MMR status was determined by a microsatellite instability assay. Among 740 patients screened, 86 were positive for MGMT promoter methylation and enrolled. Nineteen percent of the screened population (137/740) had confirmed tissue and/or serum MGMT promoter methylation, including 25% (57 of 229) for CRC, 36% (55 of 154) for esophageal cancer, 11% (12 of 113) for head and neck cancer, and 5% (13 of 242) for non-small cell lung carcinoma. Among patients with valid methylation results in both tissue and serum samples, concordance was 81% (339 of 419). The majority of enrolled patients (69 of 86; 80%) had microsatellite stable cancer. Overall RR was 6% (5 of 86 partial responses); all responders had microsatellite stable cancer. Temozolomide resulted in low RRs in patients enriched for MGMT methylation. MGMT methylation status varied considerably in the patient population. Although serum methylation assay is an option for promoter methylation detection, tissue assay remains the standard for methylation detection. The low RR of this cohort of patients indicates that MGMT methylation as a biomarker is not applicable to heterogeneous tumor types, and tumor-specific factors may override validated biomarkers.
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PMID:A phase II study of temozolomide in patients with advanced aerodigestive tract and colorectal cancers and methylation of the O6-methylguanine-DNA methyltransferase promoter. 2344 1

Temozolomide (TMZ) is a standard agent used in the treatment of various types of cancers, including lung carcinoma, but TMZ resistance is common and accounts for many treatment failures. We investigated miRNA-487b-5p (miR-487b-5p) was highly expressed in A549 and H1299 cells which acquired TMZ resistance. Suppression of miR-487b-5p had overt effects on cellular proliferation and migration in the presence of TMZ. On the other hand, knockdown of miR-487b-5p resulted in increased survival and moderate tumor growth in vivo. In addition, the decreased cellular proliferation following miR-487b-5p suppression was linked to enhanced autophagy, evident by drastically increased levels of LC3-II, BECLIN1, and LAMP2 when miR-487b-5p was knocked down. Further analysis revealed that LAMP2 might be the target gene of miR-487b-5p. In conclusion, our study suggested that miR-487b-5p may be a potential biomarker of acquired TMZ resistance in lung cancer cells, and miR-487b-5p inhibition can be further explored as a chemotherapy target in the treatment of TMZ-resistant lung carcinoma.
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PMID:miR-487b-5p Regulates Temozolomide Resistance of Lung Cancer Cells Through LAMP2-Medicated Autophagy. 2709 29

This manuscript addresses the role of O6-methylguanine-DNA methyltransferase (MGMT) as a biomarker in the oncogenesis of cancer and the opportunity of turning this gene into a drugable target in neuroendocrine tumours of the lung. Studies in brain tumours conclude that MGMT promoter methylation is considered a strong predictive factor for a favourable outcome for treatment with temozolomide, e.g. alkylating agent. We conducted a systematic review of MGMT in non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC) and other pulmonary neuroendocrine tumours (NETs) to evaluate whether MGMT is a prognostic and/or predictive factor to select patients with lung cancer who can benefit from treatment with temozolomide. In NSCLC MGMT promoter methylation is not a prognostic and predictive factor, hence temozolomide has no place. In SCLC and NET patients with a MGMT promoter methylation benefit of temozolomide has to be confirmed.Temozolomide can be considered a 'personalized' treatment if the predictive role of MGMT is further confirmed.
Lung Cancer 2017 05
PMID:O6-Methylguanine-DNA methyltransferase (MGMT): A drugable target in lung cancer? 2749 78