Somatic Genomic Mosaicism in Multiple Myeloma

Ye, Christine J.; Chen, Jason; Guo, Liang; Heng, Henry H.Q.

doi:10.3389/fgene.2020.00388

Cited by 12 publications

(13 citation statements)

References 53 publications

(85 reference statements)

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“…Despite such complexities, as recently pointed out by White-Gilbertson and Voelkel-Johnson [142], the field of cancer cell dormancy (e.g., through formation of PGCCs) "is at an exciting moment, when bench-to-bedside research has the potential to make a difference in the lives of many cancer patients." For those who are interested in further reading, we suggest seminal/recent papers on reversible cancer cell polyploidy and senescence [87,88,95,99,100,104,118,142,143] that were discussed herein as well as papers on related topics such as therapy-induced autophagy [95,144,145] and genome chaos/micronucleation [146][147][148] that were beyond the scope of the current review.…”

Section: Resultsmentioning

confidence: 99%

Cellular Responses to Platinum-Based Anticancer Drugs and UVC: Role of p53 and Implications for Cancer Therapy

Murray

Mirzayans

2020

IJMS

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Chemotherapy is intended to induce cancer cell death through apoptosis and other avenues. Unfortunately, as discussed in this article, moderate doses of genotoxic drugs such as cisplatin typical of those achieved in the clinic often invoke a cytostatic/dormancy rather than cytotoxic/apoptosis response in solid tumour-derived cell lines. This is commonly manifested by an extended apoptotic threshold, with extensive apoptosis only being seen after very high/supralethal doses of such agents. The dormancy response can be associated with senescence-like features, polyploidy and/or multinucleation, depending in part on the p53 status of the cells. In most solid tumour-derived cells, dormancy represents a long-term survival mechanism, ultimately contributing to disease recurrence. This review highlights the nonlinearity of key aspects of the molecular and cellular responses to bulky DNA lesions in human cells treated with chemotherapeutic drugs (e.g., cisplatin) or ultraviolet light-C (a widely used tool for unraveling details of the DNA damage-response) as a function of the level of genotoxic stress. Such data highlight the growing realization that targeting dormant cancer cells, which frequently emerge following conventional anticancer treatments, may represent a novel strategy to prevent or, at least, significantly suppress cancer recurrence.

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Section: Resultsmentioning

confidence: 99%

Cellular Responses to Platinum-Based Anticancer Drugs and UVC: Role of p53 and Implications for Cancer Therapy

Murray

Mirzayans

2020

IJMS

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“…It also suggests that the goal of eliminating cancer in our generation is not realistic [ 2 ]. There are many examples of such a trade-off: a large portion of liver cells change their normal karyotype to polyploidy for the liver tissue’s function; antibody production can also introduce genome-level changes outside the antibody-specific region [ 46 ]; inflammation is necessary for response to injury and infection, but is also linked to chromosomal changes, including aneuploidy [ 47 ]. All of these trade-offs, reflected in genome-level alterations, contribute to and reflect CIN.…”

Section: Cin: a Necessary Evilmentioning

confidence: 99%

“…In summary, CIN is unavoidable for advanced life systems both from internal sources (fuzzy inheritance seems to have been favored by evolution for evaluability) and environmental challenges [ 3 ]. It is essential for cellular adaptation as it can be linked to arrays of non-genomic and genomic variations, including epigenetic changes, gene mutations, copy number variations, genomic transfer among cells, chromosomal aberrations and genome chaos, and somatic mosaicism, involving many biological processes [ 13 , 46 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. Among them, some non-genomic changes, including epigenetic variations, represent a lesser degree of impact in terms of inducing CIN, and genome chaos represents an extremely high degree of impact.…”

Section: Cin: a Necessary Evilmentioning

confidence: 99%

Origins and Consequences of Chromosomal Instability: From Cellular Adaptation to Genome Chaos-Mediated System Survival

Sharpe

Heng

2020

Genes

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When discussing chromosomal instability, most of the literature focuses on the characterization of individual molecular mechanisms. These studies search for genomic and environmental causes and consequences of chromosomal instability in cancer, aiming to identify key triggering factors useful to control chromosomal instability and apply this knowledge in the clinic. Since cancer is a phenomenon of new system emergence from normal tissue driven by somatic evolution, such studies should be done in the context of new genome system emergence during evolution. In this perspective, both the origin and key outcome of chromosomal instability are examined using the genome theory of cancer evolution. Specifically, chromosomal instability was linked to a spectrum of genomic and non-genomic variants, from epigenetic alterations to drastic genome chaos. These highly diverse factors were then unified by the evolutionary mechanism of cancer. Following identification of the hidden link between cellular adaptation (positive and essential) and its trade-off (unavoidable and negative) of chromosomal instability, why chromosomal instability is the main player in the macro-cellular evolution of cancer is briefly discussed. Finally, new research directions are suggested, including searching for a common mechanism of evolutionary phase transition, establishing chromosomal instability as an evolutionary biomarker, validating the new two-phase evolutionary model of cancer, and applying such a model to improve clinical outcomes and to understand the genome-defined mechanism of organismal evolution.

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“…These BCMA-targeted agents bring therapeutic benefits to RRMM patients with advantages and disadvantages. The optimal combination and sequencing of these agents call for further studies in the future [ 53 ].…”

Section: Introductionmentioning

confidence: 99%

Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting

Hou

et al. 2021

J Hematol Oncol

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Antibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malignancies. LOXO-305, asciminib, “off-the-shelf” universal CAR-T cells and BCMA-directed immunotherapeutics as well as data from clinical trials on many novel agents and regimens were updated at the 2020 American Society of Hematology (ASH) Annual Meeting. Major developments and updates for the therapy of hematological malignancies were delineated at the recent Winter Symposium and New York Oncology Forum from the Chinese American Hematologist and Oncologist Network (CAHON.org). This study summarized the latest updates on novel agents and regimens for hematological malignancies from the 2020 ASH annual meeting.

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Somatic Genomic Mosaicism in Multiple Myeloma

Cited by 12 publications

References 53 publications

Cellular Responses to Platinum-Based Anticancer Drugs and UVC: Role of p53 and Implications for Cancer Therapy

Cellular Responses to Platinum-Based Anticancer Drugs and UVC: Role of p53 and Implications for Cancer Therapy

Origins and Consequences of Chromosomal Instability: From Cellular Adaptation to Genome Chaos-Mediated System Survival

Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting

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