The goal of this clinical research study is to learn if the combination of brigatinib and either local consolidation therapy (such as radiotherapy or surgery) or chemotherapy (pemetrexed and carboplatin) can help to control the disease compared with brigatinib alone. The safety of these combinations will also be studied.

开始日期2025-12-01

申办/合作机构

The University of Texas MD Anderson Cancer Center

100 项与 DHFR x GART x TYMS 相关的临床结果

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100 项与 DHFR x GART x TYMS 相关的转化医学

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0 项与 DHFR x GART x TYMS 相关的专利（医药）

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项与 DHFR x GART x TYMS 相关的文献（医药）

2021-04-01·Oncogene1区 · 医学

Therapeutic targeting of the mitochondrial one-carbon pathway: perspectives, pitfalls, and potential

1区 · 医学

Review

作者: Zhao, Li Na ; Caldez, Matias J ; Zheng, Jie ; Björklund, Mikael ; Kaldis, Philipp

Most of the drugs currently prescribed for cancer treatment are riddled with substantial side effects. In order to develop more effective and specific strategies to treat cancer, it is of importance to understand the biology of drug targets, particularly the newly emerging ones. A comprehensive evaluation of these targets will benefit drug development with increased likelihood for success in clinical trials. The folate-mediated one-carbon (1C) metabolism pathway has drawn renewed attention as it is often hyperactivated in cancer and inhibition of this pathway displays promise in developing anticancer treatment with fewer side effects. Here, we systematically review individual enzymes in the 1C pathway and their compartmentalization to mitochondria and cytosol. Based on these insight, we conclude that (1) except the known 1C targets (DHFR, GART, and TYMS), MTHFD2 emerges as good drug target, especially for treating hematopoietic cancers such as CLL, AML, and T-cell lymphoma; (2) SHMT2 and MTHFD1L are potential drug targets; and (3) MTHFD2L and ALDH1L2 should not be considered as drug targets. We highlight MTHFD2 as an excellent therapeutic target and SHMT2 as a complementary target based on structural/biochemical considerations and up-to-date inhibitor development, which underscores the perspectives of their therapeutic potential.

2016-04-12·Oncotarget

Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome

Article

作者: Werner, Robert ; Mairinger, Fabian Dominik ; Wohlschlaeger, Jeremias ; Vollbrecht, Claudia ; Hager, Thomas ; Christoph, Daniel Christian ; Henry Walter, Robert Fred ; Schmid, Kurt Werner

PURPOSE25% of all lung cancer cases are neuroendocrine (NELC) including typical (TC) and atypical carcinoid (AC), large-cell neuroendocrine (LCNEC) and small cell lung cancer (SCLC). Prognostic and predictive biomarkers are lacking.EXPERIMENTAL DESIGNSixty patients were used for nCounter mRNA expression analysis of the folic-acid metabolism (ATIC, DHFR, FOLR1, FPGS, GART, GGT1, SLC19A1, TYMS) and DNA-repair (ERCC1, MLH1, MSH2, MSH6, XRCC1). Phenotypic classification classified tumors (either below or above the median expression level) with respect to the folic acid metabolism or DNA repair.RESULTSExpression of FOLR1, FPGS, MLH1 and TYMS (each p<0.0001) differed significantly between all four tumor types. FOLR1 and FPGS associated with tumor differentiation (both p<0.0001), spread to regional lymph nodes (FOLR1 p=0.0001 and FPGS p=0.0038), OS and PFS (FOLR1 p<0.0050 for both and FPGS p<0.0004 for OS). Phenotypic sorting revealed the Ft-phenotype to be the most prominent expression profile in carcinoids, whereas SCLC presented nearly univocal with the fT and LCNEC with fT or ft. These results were significant for tumor subtype (p<0.0001).CONCLUSIONSThe assessed biomarkers and phenotypes allow for risk stratification (OS, PFS), diagnostic classification and enhance the biological understanding of the different subtypes of neuroendocrine tumors revealing potential new therapy options and clarifying known resistance mechanisms.

2016-04-02·Acta Oncologica

Pemetrexed and interstitial lung disease

Letter

作者: Baral, D. ; Hewett, Y. ; Adhikari, B. ; Dongol, R. M. ; Shah, B. K.

To the Editor,Pemetrexed is an antifolate chemotherapy agent that acts by inhibiting thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase [1,2]. The US F...