Dataset Information

Arginine Methylation in Brain Tumors: Tumor Biology and Therapeutic Strategies.

ABSTRACT: Protein arginine methylation is a common post-translational modification that plays a pivotal role in cellular regulation. Protein arginine methyltransferases (PRMTs) catalyze the modification of target proteins by adding methyl groups to the guanidino nitrogen atoms of arginine residues. Protein arginine methylation takes part in epigenetic and cellular regulation and has been linked to neurodegenerative diseases, metabolic diseases, and tumor progression. Aberrant expression of PRMTs is associated with the development of brain tumors such as glioblastoma and medulloblastoma. Identifying PRMTs as plausible contributors to tumorigenesis has led to preclinical and clinical investigations of PRMT inhibitors for glioblastoma and medulloblastoma therapy. In this review, we discuss the role of arginine methylation in cancer biology and provide an update on the use of small molecule inhibitors of PRMTs to treat glioblastoma, medulloblastoma, and other cancers.

SUBMITTER: Bryant JP

PROVIDER: S-EPMC7827394 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Arginine Methylation in Brain Tumors: Tumor Biology and Therapeutic Strategies.

Bryant Jean-Paul JP Heiss John J Banasavadi-Siddegowda Yeshavanth Kumar YK

Cells 20210111 1

Protein arginine methylation is a common post-translational modification that plays a pivotal role in cellular regulation. Protein arginine methyltransferases (PRMTs) catalyze the modification of target proteins by adding methyl groups to the guanidino nitrogen atoms of arginine residues. Protein arginine methylation takes part in epigenetic and cellular regulation and has been linked to neurodegenerative diseases, metabolic diseases, and tumor progression. Aberrant expression of PRMTs is associ ...[more]

PMID: 33440687

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Project description:Tumor-related activities that seem to be operationally induced by the division of function, such as inflammation, neoangiogenesis, Warburg effect, immune response, extracellular matrix remodeling, cell proliferation rate, apoptosis, coagulation effects, present itself from a systems perspective as an enhancement of complexity. We hypothesized, that tumor systems-directed therapies might have the capability to use aggregated action effects, as adjustable sizes to therapeutically modulate the tumor systems' stability, homeostasis, and robustness. We performed a retrospective analysis of recently published data on 224 patients with advanced and heavily pre-treated (10% to 63%) vascular sarcoma, melanoma, renal clear cell, cholangiocellular, carcinoma, hormone-refractory prostate cancer, and multivisceral Langerhans' cell histiocytosis enrolled in nine multi-center phase II trials (11 centers). Each patient received a multi-targeted systems-directed therapy that consisted of metronomic low-dose chemotherapy, a COX-2 inhibitor, combined with one or two transcription modulators, pioglitazone +/- dexamethasone or IFN-alpha. These treatment schedules may attenuate the metastatic potential, tumor-associated inflammation, may exert site-specific activities, and induce long-term disease stabilization followed by prolonged objective response (3% to 48%) despite poor monoactivity of the respective drugs. Progression-free survival data are comparable with those of reductionist-designed standard first-line therapies. The differential response patterns indicate the therapies' systems biological activity. Understanding systems biology as adjustable size may break through the barrier of complex tumor-stroma-interactions in a therapeutically relevant way: Comparatively high efficacy at moderate toxicity. Structured systems-directed therapies in metastatic cancer may get a source for detecting the topology of tumor-associated complex aggregated action effects as adjustable sizes available for targeted biomodulatory therapies.

Dataset Information

Arginine Methylation in Brain Tumors: Tumor Biology and Therapeutic Strategies.

Publications

Arginine Methylation in Brain Tumors: Tumor Biology and Therapeutic Strategies.

Similar Datasets

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