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Comment
. 2019 Oct 10:18:1176935119881633.
doi: 10.1177/1176935119881633. eCollection 2019.

Drug Tolerant Cells: An Emerging Target With Unique Transcriptomic Features

Divya Niveditha  1 , Harshita Sharma  1 , Anirudha Sahu  1 , Syamantak Majumder  1 , Rajdeep Chowdhury  1 , Shibasish Chowdhury  1
Affiliations
Comment

Drug Tolerant Cells: An Emerging Target With Unique Transcriptomic Features

Divya Niveditha et al. Cancer Inform. .

Abstract

Long-term outcome of cancer therapy is often severely perturbed by the acquisition of drug resistance. Recent evidence point toward the survival of a subpopulation of tumor cells under acute drug stress that over time can re-populate the tumor. These transiently existing, weakly proliferative, drug-tolerant cells facilitate tumor cell survival until more stable resistance mechanisms are acquired. From a therapeutic perspective, understanding the molecular features of the tolerant cells is critical to attenuation of resistance. In this article, we discuss the transcriptomic features of drug-tolerant osteosarcoma cells that survive a high dose of cisplatin shock. We present the unique transcriptome of the minimally dividing tolerant cells in comparison with the proliferative persisters or resistant cells derived from the tolerant cells. Targeting the tolerant cells can represent an efficient therapeutic strategy impeding tumor recurrence.

Keywords: Osteosarcoma; RNA sequencing; drug resistance; drug-tolerant persister; epigenetic alteration.

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Conflict of interest statement

Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Heatmap representing expression pattern of resistance-associated genes in cisplatin shock (OS-P) cells. The probable pathways that these genes can directly or indirectly regulate, as analyzed through KEGG database, is also indicated. KEGG indicates Kyoto Encyclopedia of Genes and Genomes; OS, osteosarcoma; OS-P, drug-tolerant persisters.
Figure 2.
Figure 2.
Volcano plot representing differential expression pattern of transcripts in OS-P cells compared with OS, along with labeled epigenetic genes. The up-regulated transcripts are in red and down-regulated transcripts are in green. Transcripts with fold change “±10” are in blue. Epigenetic genes having more or less than 10-fold differential expression are labeled. OS indicates osteosarcoma; OS-P, drug-tolerant persisters.
Figure 3.
Figure 3.
Heatmap showing the reversed expression pattern of resistance-associated genes in OS-P cells compared with OS-EP. OS indicates osteosarcoma; OS-EP, cells that resumed proliferation yielding the “extended persisters” after a drug stress; OS-P, drug-tolerant persisters.
See this image and copyright information in PMC

Comment on

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