Evidence map›Paper›PMID 36627897›Full record

ReviewCancer drug resistance (Alhambra, Calif.)2022

Drug and apoptosis resistance in cancer stem cells: a puzzle with many pieces.

Ahmad R Safa

Open access · diamondAbstract readReview
In one paragraph

Review in Cancer drug resistance (Alhambra, Calif.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 54 citations in OpenAlex.

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  19. EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

1 author at 1 institution in 1 country.

Ahmad R SafaDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Indiana University School of Medicine

Funding

Role of Proteinase-3 in Apoptosis and Drug ResistanceR01CA101743 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAFA, AHMAD R · 2003 to 2007
$1.5M
DRUG RESISTANCE DUE TO LOSS OF BETA2 MICROGLOBULINR01CA080734 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI SAFA, AHMAD R · 1999 to 2005
$1.4M
The Role of MEF1 in Multidrug ResistanceR01CA090878 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAFA, AHMAD R · 2001 to 2004
$1.1M
NCI NIH HHS R01 CA080734NCI NIH HHS R01 CA090878NCI NIH HHS R01 CA101743
6 · The paper itself

Abstract

Resistance to anticancer agents and apoptosis results in cancer relapse and is associated with cancer mortality. Substantial data have provided convincing evidence establishing that human cancers emerge from cancer stem cells (CSCs), which display self-renewal and are resistant to anticancer drugs, radiation, and apoptosis, and express enhanced epithelial to mesenchymal progression. CSCs represent a heterogeneous tumor cell population and lack specific cellular targets, which makes it a great challenge to target and eradicate them. Similarly, their close relationship with the tumor microenvironment creates greater complexity in developing novel treatment strategies targeting CSCs. Several mechanisms participate in the drug and apoptosis resistance phenotype in CSCs in various cancers. These include enhanced expression of ATP-binding cassette membrane transporters, activation of various cytoprotective and survival signaling pathways, dysregulation of stemness signaling pathways, aberrant DNA repair mechanisms, increased quiescence, autophagy, increased immune evasion, deficiency of mitochondrial-mediated apoptosis, upregulation of anti-apoptotic proteins including c-FLIP [cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein], Bcl-2 family members, inhibitors of apoptosis proteins, and PI3K/AKT signaling. Studying such mechanisms not only provides mechanistic insights into these cells that are unresponsive to drugs, but may lead to the development of targeted and effective therapeutics to eradicate CSCs. Several studies have identified promising strategies to target CSCs. These emerging strategies may help target CSC-associated drug resistance and metastasis in clinical settings. This article will review the CSCs drug and apoptosis resistance mechanisms and how to target CSCs.

Indexed as

anti-apoptotic proteinsapoptosisBcl-2 familyCancer stem cells (CSCs)c-FLIPdeath receptor pathwaysdrug resistance

Identifiers

PMID36627897
PMCPMC9771762
OpenAlexW4289536480

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.