China
Africa
Explore chapters and articles related to this topic
Targeting Subgroup-specific Cancer Epitopes for Effective Treatment of Pediatric Medulloblastoma
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sidharth Mahapatra, Naveenkumar Perumall
MYC overexpression has been linked with poor prognosis, specifically in Group 3 MB which has the highest incidence of MYC overexpression [2, 34, 70, 78, 79]. The overall incidence of MYC amplification in Group 3 MB is approximately 10-17% [65]. Studies that combined whole genome sequencing with transcription profiling shed light on the role of epigenetic silencing in the development of Group 3 and 4 MB; they revealed the importance of transcriptional silencing of histones [80] . A clustering of mutations influencingthe methylation of H3K27 (histone H3 lysine 27) and H3K4 (histone 3 lysine 4) was noted and linked with tumor stemness and invasiveness [75, 76]. MYC is a strong activator of EZH2, an H3K27 methyl-transferase, overexpressed in non-SHH/WNT MB [75, 81]. Both proteins promote stem-like states and antagonize the process of neural cell differentiation, leading to elevations in stem cell markers, Oct4, Sox2, and Nanog [82, 83]. These markers have, in turn, been associated with aggressiveness of MB [83]. Thus, a link between high MYC expression and tumor aggressiveness has been elucidated from these studies. In turn, MYC deprivation in orthotopic xenograft models of non-SHH/WNT MB has demonstrated tumor cell senescence and apoptosis [84]. As a result, MYC targeting has become a preferred model of study for the generation of targeted therapeutics in non-SHH/WNT MB.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Many heritable diseases result from DNA mutations that block gene expression, although some disorders are caused by epigenetic modifications that cause gene silencing. For example, cancer cells can invoke the epigenetic silencing of tumor suppressor genes that would normally block tumorigenesis. Similarly, inappropriate gene activation can also lead to diseases. For example, Burkitt’s lymphoma is caused by overexpression of myc, the function of which is to promote cell proliferation. As might be anticipated, in healthy cells the myc gene is usually located in an area of “closed” chromatin, as expression is not required. However, in affected lymphocytes, an epigenetic change can move the myc gene into a region of “open” chromatin through abnormal chromosomal rearrangements, thus leading to overexpression and stimulation of the unregulated proliferation of lymphocytes, leading to the clinical symptoms of lymphoma.
Oncogenes and Cancer
Published in Pimentel Enrique, Oncogenes, 2020
In some of the above mentioned tumor cell lines, numerous DMs chromosomes and HSRs chromosomes were observed. Since such cytogenetic abnormalities are present in a number of tumor cell lines, as well as in direct preparations of tumor specimens,130-135 they might correspond to amplification of certain proto-oncogenes and perhaps also of other genes. In some tumor cell lines no DMs or HSRs have been observed in spite of the presence of amplification of proto-oncogenes,129 but in other cell lines an association between these cytogenetic abnormalities and amplification of specific oncogene has been established. For example, the c-myc gene was found to be amplified in cell lines derived from human neuroblastomas and by means of in situ molecular hybridization it was demonstrated that HSRs are the chromosomal sites of amplified DNA.115 However, the degree of amplification varied considerably between different human neuroblastoma cell lines (from 5- to 8-fold or 12- to 140-fold), and in one cell line no such amplification was detected (it was also not detected in cell lines derived from human melanoma, retinoblastoma and colon carcinoma). Whereas the c-myc gene is normally located on human chromosome 8q, the detected amplified sequences, that included a domain distantly related to c-myc, occupied different chromosomal locations.112
Gene expression analysis and the risk of relapse in favorable histology Wilms’ tumor
Published in Arab Journal of Urology, 2023
Mariam M. Abdel-Monem, Omali Y. El-Khawaga, Amira A. Awadalla, Ashraf T. Hafez, Asmaa E. Ahmed, Mohamed Abdelhameed, Ahmed Abdelhalim
c-MYC is capable of driving cellular proliferation or apoptosis depending on other cellular signals. It stimulates cellular proliferation, glycolysis, mitochondrial biogenesis and malignant transformation. c-MYC is overexpressed in many neoplastic diseases, either due to mutation of its gene or due to the induction of its expression by a number of upstream oncogenic pathways. Both c-MYC and HIF1α act together to promote cancer cell growth and progression. c-MYC overexpression could be responsible for the increased cellular metabolism induced by malignant transformation or the result of complex metabolic changes that occur when cells turn malignant [19]. We have observed elevated bFGF and c-MYC levels in WT tissue compared to autologous renal tissue with significantly higher levels in tumors that relapsed.
The evolution of cyclin dependent kinase inhibitors in the treatment of cancer
Published in Expert Review of Anticancer Therapy, 2021
Komal Jhaveri, Howard A Burris 3rd, Timothy A Yap, Erika Hamilton, Hope S Rugo, Jonathan W Goldman, Stephen Dann, Feng Liu, Gilbert Y Wong, Heike Krupka, Geoffrey I Shapiro
Tumor metabolic reprogramming appears to be an important factor in adaptive responses to drug‐induced stress and may reveal weaknesses of cancer cells [122,123]. A study combining metabolic analysis with transcriptomic data found metabolic changes associated with CDK4/6 depletion, reporting that MYC upregulation and its downstream network, which includes mTOR signaling and glutaminolysis, is an adaptation to CDK4/6 inhibition [124]. MYC overexpression is associated with drug resistance, and reduction or inhibition of CDK4/6 in cancer cells can result in de novo addiction to MYC, and to glutaminase and mTOR signaling, and a compromised adaptation to hypoxia [124]. Of particular note, Hydbring et al. described direct phosphorylation of MYC by CDK2/Cyclin E as a mechanism for overcoming Ras driven oncogene induced senescence [125,126]. In addition, CDK2 knockout mice displayed prolonged survival in the Emu-MYC background, correlating with increased cellular senescence [127]. Therapeutic combinations of CDK4/6 inhibitors with agents depleting MYC mRNA or protein may exploit these dependencies. MYC stabilization can be mediated by AURKA activity where it drives G2/M cell cycle progression and inhibition of AURKA results in degradation of MYC protein [128]. In 11/41 HR+ breast cancer patients who were refractory to CDK4/6 inhibitor therapy, AURKA amplification was observed and likely contributed to CDK4/6 inhibitor resistance [88]. Amplification and overexpression of MYC may also be targeted by CDK1 inhibition, CDK9 inhibition, or BET bromodomain inhibition [29,30,129,130].
Identification of Key mRNAs and Pathways in Colorectal Cancer
Published in Nutrition and Cancer, 2021
Xiaolin Hou, Nengyi Hou, Junwen Fu, Xuelai He, Haibo Xiong, Wei Xie, Guiqing Jia, Xiaofei Zuo, Xianpeng Qin, Minghui Pang
Hub gene was identified by the PPI network, the upregulated genes, include TOP2A, MYC, and PAICS, and the downregulated genes, including AKT1, ACTB, CALM1, UBC, MYH14, CYCS, and TGFB1. For the upregulated genes, TOP2A is a DNA topoisomerase, the gene encoding this enzyme functions as the target for several anticancer agents. MYC is a family of regulator genes and proto-oncogenes that code for transcription factors. PAICS is a novel cancer metabolic target, which is essential for the cancer cell. For the downregulated genes, Akt is a downstream mediator of the PI 3-K pathway, which results in the recruitment of Akt to the plasma membrane, in human protein atlas (https://www.proteinatlas.org/), CALM1, TGFB1, and UBC, the low expression is associate with poor prognostics. These hub genes may play a vital role in cancer cell development and metabolism.