<scp>MYC</scp> and therapy resistance in cancer: risks and opportunities

Donati, Giulio; Amati, Bruno

doi:10.1002/1878-0261.13319

Cited by 38 publications

(31 citation statements)

References 392 publications

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“…GSEA showed that E2F, MYC, mTORC1, glycolysis and mitotic spindle were significantly enriched in CRA. E2F and MYC played a vital role in the proliferation of tumor cells [ 24 , 25 ]. mTORC1 is involved in the metabolic regulation of tumors, and the upregulation of glycolysis is an essential feature of tumor metabolic reprogramming [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and clinical validation of key genes as the potential biomarkers in colorectal adenoma

et al. 2023

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Background Colorectal cancer (CRC), ranking third in cancer prevalence and second in mortality worldwide, is mainly derived from colorectal adenoma (CRA). CRA is a common benign disease in the intestine with rapidly increasing incidence and malignant potential. Therefore, this study aimed to recognize significant biomarkers and original pathogenesis in CRA. Methods Transcriptome data of GSE8671, GSE37364, and GSE15960 were downloaded from the Gene Expression Omnibus (GEO) datasets, and differentially expressed genes (DEGs) were screened. Functional pathways enrichment, protein–protein interaction (PPI) network, stem-correlation analysis, CIBERSORT, risk score and survival analyses were performed. RT-qPCR and immunohistochemical staining were applied to verify our results. Results Screening for significant DEGs in each dataset, we identified 230 robust DEGs, including 127 upregulated and 103 downregulated genes. Functional pathways enrichment showed that these DEGs were distinctly enriched in various tumor-associated pathways, such as growth factor activity, extracellular structure organization, neutrophil activation, and inflammatory response. We filtered out two hub genes via STRING and Modules analysis, including CA2 and HSD11B2. Stem-correlation analysis displayed that hub genes were negatively associated with stem-related genes (Olfm4, CD44, CCND1 and MYC). The CIBERSORT algorithm indicated that Macrophage2, activated mast cells, and Neutrophils promoted CRA progression through inflammation. Survival analysis showed that CA2 and HSD11B2 were positively associated with survival outcomes in CRC. Conclusion Our study has successfully identified the critical role of two core genes in the development and oncogenesis of CRA, which provides novel insight into the underlying pathogenesis, potential biomarkers and therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Identification and clinical validation of key genes as the potential biomarkers in colorectal adenoma

et al. 2023

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“…After JAK2/STAT3 inhibition, we observed a decrease in c-MYC protein expression in sarcoma cells treated with LFU and PTX combination in vitro . c-MYC is one of the common proto-oncogenes and plays an important role as a transcription factor in cell cycle and cell proliferation ( Donati and Amati, 2022 ). Previous studies have shown that MYC can bind directly to the promoter of PD-L1 gene, while PD-L1 can inhibit T cell responses in the tumor microenvironment, and further found that MYC inactivation in mouse tumors can down-regulate the expression of PD-L1 and enhance anti-tumor immune responses.…”

Section: Discussionmentioning

confidence: 99%

Low-frequency ultrasound irradiation increases paclitaxel-induced sarcoma cells apoptosis and facilitates the transmembrane delivery of drugs

et al. 2022

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Sarcoma is a malignant tumor derived from interstitial tissues and requires comprehensive treatment including chemotherapy. Paclitaxel (PTX) is an active agent against sarcoma, but its effect is not sufficiently acceptable and needs to be improved. Low-frequency ultrasound (LFU) has been documented to improve the efficacy of drugs by inducing reversible changes in membrane permeability; however, the effects of the combined use of LFU and PTX for sarcoma tumors remain unclear and warrant further investigation. We investigated the effects of 30 kHz LFU treatment combined with PTX on sarcoma cells A-204 and HT-1080 by analyzing in vitro apoptosis and cell growth inhibition rates, and determined their antitumor effects by examining tumor weights with or without LFU in the S180 sarcoma xenograft model. Drug concentrations in the subcutaneous tumors were measured using high performance liquid chromatography (HPLC). LFU combined with PTX significantly induced cell apoptosis, and blocked the cell cycle of sarcoma cells in G2/M phase, and furthermore, inhibited the activation of JAK2/STAT3 signaling pathway. Meanwhile, LFU combined with PTX inhibited the expression of PD-L1 in vitro, suggesting the potential of enhanced antitumor immunity by this treatment. LFU combined with PTX significantly inhibited the growth of S180 tumors transplanted subcutaneously in Institute of Cancer Research (ICR) mice, and its enhanced effect may be associated with increased local concentrations of PTX in tumor tissues in vivo, with no significant adverse subsequences on body weight observed. We conclude that the combination of LFU and PTX has synergistic antitumor effects and is a candidate for subcutaneous treatment of sarcoma by further increasing the intracellular concentration of PTX.

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“…Hence, MYC is still classified as a “difficult-to-drug” or even “undruggable” therapeutic target ( 113 ). All current possibilities to directly or indirectly inhibit oncogenic MYC are comprehensively summarized in recent excellent reviews ( 18 , 109 , 114 ). A description and illustration of selected principles and methods to inhibit MYC ( Figure 3 ) are given below.…”

Section: Myc: An Oncogenic Transcription Factor With Pleiotropic Func...mentioning

confidence: 99%

“…In fact, oncogenic MYC offers multiple molecular and metabolic dependencies, which could be exploited to target relevant synthetic-lethal interactions ( 114 ). An example is a recent screen of more than 800 protein kinase inhibitors, which influence the stability of the MYC protein.…”

Section: Myc: An Oncogenic Transcription Factor With Pleiotropic Func...mentioning

confidence: 99%

Strategies to target the cancer driver MYC in tumor cells

Weber

Hartl

2023

Front. Oncol.

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The MYC oncoprotein functions as a master regulator of cellular transcription and executes non-transcriptional tasks relevant to DNA replication and cell cycle regulation, thereby interacting with multiple proteins. MYC is required for fundamental cellular processes triggering proliferation, growth, differentiation, or apoptosis and also represents a major cancer driver being aberrantly activated in most human tumors. Due to its non-enzymatic biochemical functions and largely unstructured surface, MYC has remained difficult for specific inhibitor compounds to directly address, and consequently, alternative approaches leading to indirect MYC inhibition have evolved. Nowadays, multiple organic compounds, nucleic acids, or peptides specifically interfering with MYC activities are in preclinical or early-stage clinical studies, but none of them have been approved so far for the pharmacological treatment of cancer patients. In addition, specific and efficient delivery technologies to deliver MYC-inhibiting agents into MYC-dependent tumor cells are just beginning to emerge. In this review, an overview of direct and indirect MYC-inhibiting agents and their modes of MYC inhibition is given. Furthermore, we summarize current possibilities to deliver appropriate drugs into cancer cells containing derailed MYC using viral vectors or appropriate nanoparticles. Finding the right formulation to target MYC-dependent cancers and to achieve a high intracellular concentration of compounds blocking or attenuating oncogenic MYC activities could be as important as the development of novel MYC-inhibiting principles.

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MYC and therapy resistance in cancer: risks and opportunities

Cited by 38 publications

References 392 publications

Identification and clinical validation of key genes as the potential biomarkers in colorectal adenoma

Identification and clinical validation of key genes as the potential biomarkers in colorectal adenoma

Low-frequency ultrasound irradiation increases paclitaxel-induced sarcoma cells apoptosis and facilitates the transmembrane delivery of drugs

Strategies to target the cancer driver MYC in tumor cells

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