Effect of stress-induced polyploidy on melanoma reprogramming and therapy resistance

Meierjohann, Svenja

doi:10.1016/j.semcancer.2021.02.005

Cited by 12 publications

(2 citation statements)

References 154 publications

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“…It has been recently shown that PGCCs recapitulate properties of the blastomere-stage embryonic program of dedifferentiation (16,20,22,24,25). PGCCs are also known to contribute to therapy resistance in various types of solid tumors, including ovarian (16), prostate (19,(26)(27)(28), colon (29), and breast cancers (30) and melanoma (31). However, whether PGCCs account for resistance to PARPi in HGSC remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Targeting polyploid giant cancer cells potentiates a therapeutic response and overcomes resistance to PARP inhibitors in ovarian cancer

Zhang

Yao

et al. 2023

Sci. Adv.

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To understand the mechanism of acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) olaparib, we induced the formation of polyploid giant cancer cells (PGCCs) in ovarian and breast cancer cell lines, high-grade serous cancer (HGSC)–derived organoids, and patient-derived xenografts (PDXs). Time-lapse tracking of ovarian cancer cells revealed that PGCCs primarily developed from endoreplication after exposure to sublethal concentrations of olaparib. PGCCs exhibited features of senescent cells but, after olaparib withdrawal, can escape senescence via restitutional multipolar endomitosis and other noncanonical modes of cell division to generate mitotically competent resistant daughter cells. The contraceptive drug mifepristone blocked PGCC formation and daughter cell formation. Mifepristone/olaparib combination therapy substantially reduced tumor growth in PDX models without previous olaparib exposure, while mifepristone alone decreased tumor growth in PDX models with acquired olaparib resistance. Thus, targeting PGCCs may represent a promising approach to potentiate the therapeutic response to PARPi and overcome PARPi-induced resistance.

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Section: Introductionmentioning

confidence: 99%

Targeting polyploid giant cancer cells potentiates a therapeutic response and overcomes resistance to PARP inhibitors in ovarian cancer

Zhang

Yao

et al. 2023

Sci. Adv.

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“…Melanoma derives from the genetic mutations in melanocytes, existing in the skin, eye, inner ear, and leptomeninges (1)(2)(3). Uveal melanoma (UM) is a rare ocular malignant tumor with a rapidly increasing incidence worldwide (4).…”

Section: Introductionmentioning

confidence: 99%

Integration of Bulk RNA Sequencing and Single-Cell RNA Sequencing to Reveal Uveal Melanoma Tumor Heterogeneity and Cells Related to Survival

et al. 2022

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Molecular classification based on transcriptional characteristics is often used to study tumor heterogeneity. Human cancer has different cell populations with distinct transcription in tumors, and their heterogeneity is the focus of tumor therapy. Our purpose was to explore the tumor heterogeneity of uveal melanoma (UM) through RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq). Based on the consensus clustering assays of the prognosis-related immune gene set, the immune subtype (IS) of UM and its corresponding immune characteristics were comprehensively analyzed. The heterogeneous cell groups and corresponding marker genes of UM were identified from GSE138433 using scRNA-seq analysis. Pseudotime trajectory analysis and SCENIC analysis were conducted to explore the trajectory of cell differentiation and the regulatory network of single-cell transcription factors (TFs). Based on 37 immune gene sets, UM was divided into two different immune subtypes (IS1 and IS2). The two kinds of ISs have different characteristics in prognosis, immune-related molecules, immune score, and immune cell infiltration. According to 11,988 cells of scRNA-seq data from six UM samples, 11 cell clusters and 10 cell types were identified. The subsets of C1, C4, C5, C8, and C9 were related to the prognosis of UM, and different TF–target gene regulatory networks were involved. These five cell subsets differentiated into 3 different states. Our results provided valuable information about the heterogeneity of UM tumors and the expression patterns of TFs in different cell types.

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Characterization of polyploidy in cancer: Current status and future perspectives

Ghosh,

Choudhury,

Ghosh

et al. 2024

International Journal of Biological Macromolecules

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Effect of stress-induced polyploidy on melanoma reprogramming and therapy resistance

Cited by 12 publications

References 154 publications

Targeting polyploid giant cancer cells potentiates a therapeutic response and overcomes resistance to PARP inhibitors in ovarian cancer

Targeting polyploid giant cancer cells potentiates a therapeutic response and overcomes resistance to PARP inhibitors in ovarian cancer

Integration of Bulk RNA Sequencing and Single-Cell RNA Sequencing to Reveal Uveal Melanoma Tumor Heterogeneity and Cells Related to Survival

Characterization of polyploidy in cancer: Current status and future perspectives

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