Targeting GLS1 to cancer therapy through glutamine metabolism

AbstractGlutamine metabolism is one of the hallmarks of cancers which is described as an essential role in serving as a major energy and building blocks supply to cell proliferation in cancer cells. Many malignant tumor cells always display glutamine addiction. The “kidney-type” glutaminase (GLS1) is a metabolism enzyme which plays a significant part in glutaminolysis. Interestingly, GLS1 is often overexpressed in highly proliferative cancer cells to fulfill enhanced glutamine demand. So far, GLS1 has been proved to be a significant target during the carci nogenesis process, and emerging evidence reveals that its inhibitors could provide a benefit strategy for cancer therapy. Herein, we summarize the prognostic value of GLS1 in multiple cancer type and its related regulatory factors which are associated with antitumor activity. Moreover, this review a rticle highlights the remarkable reform of discovery and development for GLS1 inhibitors. On the basis of case studies, our perspectives for targeting GLS1 and development of GLS1 antagonist are discussed in the final part.
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research

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AbstractGlutamine metabolism is one of the hallmarks of cancers which is described as an essential role in serving as a major energy and building blocks supply to cell proliferation in cancer cells. Many malignant tumor cells always display glutamine addiction. The “kidney-type” glutaminase (GLS1) is a metabolism enzyme which plays a significant part in glutaminolysis. Interestingly, GLS1 is often overexpressed in highly proliferative cancer cells to fulfill enhanced glutamine demand. So far, GLS1 has been proved to be a significant target during the carci nogenesis process, and emerging evidence reveals that i...
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
Oncotarget. 2021 Aug 31;12(18):1821-1835. doi: 10.18632/oncotarget.28049. eCollection 2021 Aug 31.ABSTRACTSenolytics are basically anti-cancer drugs, repurposed to kill senescent cells selectively. It is even more difficult to selectively kill senescent cells than to kill cancer cells. Based on lessons of cancer therapy, here I suggest how to exploit oncogene-addiction and to combine drugs to achieve selectivity. However, even if selective senolytic combinations will be developed, there is little evidence that a few senescent cells are responsible for organismal aging. I also discuss gerostatics, such as rapamycin and othe...
Source: Oncotarget - Category: Cancer & Oncology Authors: Source Type: research
s Roa Viviana P. Montecinos Alfonso Gonzalez Cancer therapy may be improved by the simultaneous interference of two or more oncogenic pathways contributing to tumor progression and aggressiveness, such as EGFR and p53. Tumor cells expressing gain-of-function (GOF) mutants of p53 (mutp53) are usually resistant to EGFR inhibitors and display invasive migration and AKT-mediated survival associated with enhanced EGFR recycling. D-Propranolol (D-Prop), the non-beta blocker enantiomer of propranolol, was previously shown to induce EGFR internalization through a PKA inhibitory pathway that blocks the recycling of the rece...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
err Drug resistance is a major cause of cancer treatment failure, effectively driven by processes that promote escape from therapy-induced cell death. The mechanisms driving evasion of apoptosis have been widely studied across multiple cancer types, and have facilitated new and exciting therapeutic discoveries with the potential to improve cancer patient care. However, an increasing understanding of the crosstalk between cancer hallmarks has highlighted the complexity of the mechanisms of drug resistance, co-opting pathways outside of the canonical “cell death” machinery to facilitate cell survival in the f...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Source: Lung Cancer - Category: Cancer & Oncology Authors: Tags: NSCLC Chemotherapy Source Type: research
ConclusionsOur data indicate that exploring BC gene regulatory mechanisms associated with SEs through integrating RNA-seq and ChIP-seq data improves our understanding of BC biology and provides a basis for innovative therapies.
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research
ConclusionMET was found to be cytotoxic in GBM cells in vitro only at high, clinically not relevant concentrations, where it was effective in inducing apoptosis and necrosis. Sensitizing effects were only observed in combination with doxorubicin, but not with TMZ, and are dependent on cell line and the applied drug concentration. Therefore, our findings do not support the use of MET in the treatment of GBM in combination with TMZ, as no sensitizing effect of MET was observed.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, we found that regardless of the presence of multimorbidity, engaging in a healthier lifestyle was associated with up to 6.3 years longer life for men and 7.6 years for women; however, not all lifestyle risk factors equally correlated with life expectancy, with smoking being significantly worse than others. A Hydrogel Scaffold to Encourage Peripheral Nerve Regeneration https://www.fightaging.org/archives/2020/10/a-hydrogel-scaffold-to-encourage-peripheral-nerve-regeneration/ The nervous system of mammals is poorly regenerative at best. The use of implantable scaffold materials is one of the...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ich The nucleolus has been known for a long time to fulfill crucial functions in ribosome biogenesis, of which cancer cells can become addicted to in order to produce sufficient amounts of proteins for cell proliferation. Recently, the nucleolus has emerged as a central regulatory hub in many other cancer-relevant processes, including stress sensing, DNA damage response, cell cycle control, and proteostasis. This fostered the idea that nucleolar processes can be exploited in cancer therapy. Interestingly, a significant proportion of poly(ADP-ribose) polymerase 1 (PARP1) molecules are localized in the nucleolus and PARP...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Lung cancer is the leading cause of cancer death worldwide. Cigarette smoking is the most common risk factor for lung carcinoma; other risks include genetic factors and exposure to radon gas, asbestos, secondhand smoke, and air pollution. Nicotine, the primary addictive constituent of cigarettes, contributes to cancer progression through activation of nicotinic acetylcholine receptors (nAChRs), which are membrane ligand-gated ion channels. Activation of nicotine/nAChR signaling is associated with lung cancer risk and drug resistance. We focused on nAChR pathways activated by nicotine and its downstream signaling involved i...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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