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PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
This process is orchestrated by autophagy-related genes (ATGs), evolutionarily conserved from yeast to mammals .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Initiation occurs under nutrient deprivation or stress, leading to mTORC1 inactivation and activation of the ULK1/2 complex .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The ULK complex, comprising ULK1/2, ATG13, and ATG101, promotes phagophore formation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
PI3P production by the VPS34 complex I, modulated by Bcl-2, recruits WIPI proteins and facilitates Atg12-Atg5-Atg16L1 complex formation, driving LC3 lipidation and autophagosome maturation .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Autophagy exhibits a context-dependent dual role in tumor biology.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
On the one hand, it functions as a cytoprotective mechanism under metabolic and oxidative stress, enabling tumor cells to sustain viability under hypoxia, nutrient scarcity, or therapeutic insult .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In GIST, c-KIT mutations are associated with aberrant autophagy activation, enhancing resistance to apoptosis and contributing to therapeutic resistance .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Enhanced autophagic flux under stress conditions delays senescence, facilitates immune evasion, and sustains tumor proliferation .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Conversely, persistent or excessive autophagy may elicit autophagic cell death.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In GIST, knockout of ATGs such as ATG7 sensitizes tumor cells to IM, highlighting autophagy as a mechanism of drug resistance and a potential therapeutic target .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Elevated expression of autophagy markers correlates with unfavorable prognosis in several cancers .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Inhibition of autophagy using lysosomal blockers like chloroquine impedes autophagosome-lysosome fusion, potentiating IM-induced cytotoxicity .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
This dualistic nature of autophagy underscores its therapeutic complexity and offers the potential for context-specific modulation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Research on the therapeutic effects of IM in GISTs has traditionally emphasized its capacity to induce apoptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
However, apoptosis and autophagy, often initiated by overlapping upstream signaling pathways, engage in distinct and sometimes opposing cellular functions.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Apoptosis is widely recognized as a tumor-suppressive mechanism, whereas the role of autophagy remains context-dependent, influenced by tumor stage, oncogenic mutations, and microenvironmental conditions .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Emerging evidence suggests that IM resistance may be mediated, at least in part, through autophagy, regulated by various molecular factors, including ncRNAs .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Accordingly, elucidating the interplay between TKI-induced autophagy and apoptosis in GISTs may uncover novel strategies to overcome drug resistance (Fig. 3).Fig.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
3Role of Autophagy in GIST Cell Drug Resistance (Created by BioRender).
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
This figure explores the response of GIST cells to IM treatment.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Autophagy levels significantly increase post-treatment, especially in drug-resistant GIST cells.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Chloroquine, an autophagy inhibitor, may promote apoptosis by blocking autophagy, suggesting potential therapeutic effects Role of Autophagy in GIST Cell Drug Resistance (Created by BioRender).
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
This figure explores the response of GIST cells to IM treatment.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Autophagy levels significantly increase post-treatment, especially in drug-resistant GIST cells.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Chloroquine, an autophagy inhibitor, may promote apoptosis by blocking autophagy, suggesting potential therapeutic effects A pivotal study by Miselli et al. (2008) examined surgical specimens from 11 GIST patients with confirmed molecular characteristics who received IM therapy, compared to 2 untreated patients.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The IM-treated group exhibited elevated expression of the pre-autophagic marker Beclin1/PI3KIII and reduced anti-autophagic Beclin1/Bcl-2 complex levels.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Notably, apoptosis-related proteins were undetectable in these samples.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These findings suggest that in untreated tumors, IM may induce anti-tumor activity via KIT autophagy, whereas in pretreated tumors, a subset of GIST cells may transition into a quiescent state-retaining proliferative potential upon IM discontinuation or acquisition of resistance mutations .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Further supporting this notion, Gupta et al. demonstrated that GIST cell survival and dormancy during IM therapy are associated with a stabilized tumor burden.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Despite limited apoptotic induction by IM, autophagic vesicle formation was observed as early as 8 h post-treatment, particularly in IM-sensitive cells.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Importantly, a negative correlation between autophagy and apoptosis was established.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These findings underscore autophagy's critical role in maintaining GIST cells in a quiescent, reversible, non-proliferative state.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
This dormancy allows tumor cells to withstand intrinsic vulnerabilities and therapeutic stress, ultimately contributing to recurrence and the development of drug resistance.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Autophagy is tightly regulated by several signaling pathways, among which mTOR and AMP-activated protein kinase (AMPK) are the most prominent.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The mechanistic target of rapamycin (mTOR) serves as a negative regulator of autophagy by integrating upstream signals such as PI3K/Akt.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
It suppresses autophagy initiation by phosphorylating ULK1 complex components, including ULK1 and Atg13.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In GIST, hyperactivation of mTOR correlates with increased tumor growth, invasiveness, and therapeutic resistance.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Notably, mTOR signaling enhances cellular metabolism and restrains autophagic cell death, contributing to treatment evasion .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
As a result, mTOR inhibitors like rapamycin have been widely explored as modulators of autophagy and potential anticancer agents.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Rapamycin has demonstrated efficacy in suppressing GIST cell proliferation and enhancing chemotherapy sensitivity .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Conversely, AMPK functions as a cellular energy sensor and positive regulator of autophagy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Under energy stress, AMPK inhibits mTOR signaling and directly activates autophagy to restore metabolic homeostasis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In GIST, AMPK activation has been shown to inhibit tumor cell proliferation and promote apoptosis while enhancing autophagy and alleviating mTOR-mediated suppression .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Beyond autophagy induction, AMPK modulates lipid metabolism and glycolysis, creating a more vulnerable metabolic state in tumor cells.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Small-molecule AMPK activators have improved chemotherapeutic responses in preclinical GIST models, highlighting their potential as therapeutic agents .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In summary, mTOR and AMPK are opposing autophagy regulators and play critical roles in GIST pathogenesis and drug response.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Therapeutically targeting this regulatory axis offers promising opportunities to overcome resistance in GIST and other malignancies.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Silencing of autophagy-related genes ATG7 and ATG12 via RNA interference, or pharmacological inhibition of lysosomes using antimalarial agents, has synergized with IM to induce GIST cell death .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Song et al. reported that autophagy activity is significantly elevated in IM-resistant GIST cell lines compared to sensitive ones.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Importantly, co-treatment with chloroquine, a lysosomal inhibitor, and IM suppressed autophagy via the MAPK/ERK pathway, enhancing cytotoxicity and overcoming drug resistance .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Chloroquine disrupts autophagosome-lysosome fusion, and its combination with IM reduces LC3-II expression, increases chemotherapy sensitivity, and exerts potent tumor-suppressive effects in GIST mouse models (Fig. 3).
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Beyond lysosomal inhibition, targeting heat shock proteins (HSPs) has emerged as another promising strategy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
As molecular chaperones, HSPs stabilize oncogenic proteins such as mutant KIT.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Inhibition of HSP90 using NVP-AUY922 (AUY922) facilitates KIT degradation via proteasomal and autophagic pathways.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
AUY922 effectively suppresses the growth of both IM-sensitive (GIST882) and IM-resistant (GIST48) cells.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
However, when autophagy is blocked, the KIT protein accumulates, highlighting the critical role of autophagy in KIT turnover induced by HSP90AA1 inhibition .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Subsequent studies demonstrated that rapamycin, an mTOR inhibitor, reduces total and phosphorylated KIT levels in IM-resistant GIST cells.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Combined treatment with rapamycin and AUY922 produces a synergistic antiproliferative effect in vitro .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Mechanistically, the tyrosine kinase WEE1 promotes KIT degradation by repressing Beclin1 and enhancing the LC3BII/I ratio, thus facilitating autophagic flux .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
A reciprocal relationship between autophagy and apoptosis has been widely observed in GIST.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The X-linked inhibitor of apoptosis protein (XIAP), which suppresses apoptosis, becomes stabilized in IM-treated GIST-882 cells due to decreased ubiquitination.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
It is accompanied by increased autophagy, suggesting that the ubiquitin–proteasome system may modulate autophagic activity and contribute to secondary resistance .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Autophagy regulation also involves post-translational and epigenetic mechanisms.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
ATG5 is stabilized by the deubiquitinase USP13 in a PAK1-dependent manner, with USP13 is transcriptionally regulated by the methyltransferase METTL3 .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In addition, recent studies have uncovered a neurotrophic signaling axis in GIST.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The GDNF-GFRA1 pathway interacts with the lysosomal calcium channel MCOLN1, activating Ca-dependent TFEB signaling.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
TFEB subsequently upregulates lysosomal gene expression, amplifies autophagic flux, and inhibits apoptosis under TKI treatment.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Dual inhibition of GFRA1 and autophagy demonstrates promising potential for overcoming drug resistance in GIST therapy .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Ferroptosis is a distinct form of PCD characterized by iron-dependent lipid peroxidation and reactive oxygen species (ROS) accumulation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Unlike apoptosis or necrosis, ferroptosis is driven by intracellular iron overload, which catalyzes Fenton reactions to generate hydroxyl radicals that damage polyunsaturated fatty acids (PUFAs) in membrane phospholipids, ultimately leading to cell death .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Beyond its role in tumor suppression, ferroptosis is implicated in various pathological conditions, including neurodegenerative, cardiovascular, and hepatic diseases.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
A central ferroptosis regulator is glutathione peroxidase 4 (GPX4), which protects cells by reducing lipid peroxides.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Inhibition or loss of GPX4 function induces ferroptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The small-molecule RSL3 is a well-characterized GPX4 inhibitor that irreversibly inactivates GPX4, promoting lipid peroxidation and cell death.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
RSL3 has shown potent anti-tumor activity across multiple cancer models and enhances chemotherapy efficacy, particularly in drug-resistant tumors .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Co-administration with other ferroptosis inducers, such as FIN56, amplifies tumor cell death .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Furthermore, GPX4 inhibitors elevate ROS levels, stimulate T and NK cell activation, and improve tumor immune surveillance .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In vivo studies confirm their tolerability and efficacy against solid tumors, including GIST .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Ferroptosis induction in GIST is primarily mediated by ROS generated through mitochondrial respiration and the NADPH oxidase (NOX) family.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These ROS disrupt membrane integrity, triggering ferroptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Their clearance depends largely on the xc-glutathione (GSH)-GPX4 axis, with additional antioxidant inputs from coenzyme Q10 and tetrahydrobiopterin (Fig. 4).
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
GPX4 utilizes GSH, supplied by cysteine imported through the xc cystine/glutamate antiporter system, to neutralize lipid ROS and maintain redox homeostasis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Fig. 4Metabolic Regulation and Drug Targets in Ferroptosis Pathway (Created by BioRender).
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
This figure outlines the key molecular mechanisms of the ferroptosis pathway, including the interactions between GSH, PUFAs, and iron ions.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Drugs such as IM and vorinostat may also enhance anti-tumor effects by modulating ferroptosis-related pathways Metabolic Regulation and Drug Targets in Ferroptosis Pathway (Created by BioRender).
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
This figure outlines the key molecular mechanisms of the ferroptosis pathway, including the interactions between GSH, PUFAs, and iron ions.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Drugs such as IM and vorinostat may also enhance anti-tumor effects by modulating ferroptosis-related pathways The xc antiporter consists of SLC7A11 (xCT) and SLC3A2 subunits, which exchange extracellular cystine for intracellular glutamate .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These transporters are crucial in regulating redox balance, iron metabolism, and susceptibility to ferroptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Targeting GPX4 or SLC7A11 has emerged as a promising strategy to sensitize GIST cells to chemotherapy via ferroptosis induction.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Nevertheless, issues such as treatment specificity and resistance remain challenges for future clinical applications.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In addition to GPX4 and SLC7A11, ferroptosis is modulated by proteins involved in iron homeostasis, such as hepcidin and ferritin, which control intracellular iron availability .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Increasing evidence highlights ferroptosis as a novel therapeutic avenue, especially in tumors unresponsive to conventional chemotherapy or targeted therapy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Agents like RSL3 activate ferroptosis pathways and effectively inhibit tumor cell proliferation .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
However, the context-dependent nature of ferroptosis and its specific regulatory mechanisms in different tumor types warrant further investigation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The redox state of intracellular iron significantly influences cellular sensitivity to ferroptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Additionally, the cytoskeleton, modulated by phosphorylation of heat shock protein family B member 1 (HSPB1), plays a role in iron uptake and lipid ROS generation .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Before the introduction of IM, inhibitors of HSPs attracted attention as potential therapeutics.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
For example, the HSP90 inhibitor IPI-504 was shown to induce KIT degradation, suppress cell proliferation, and reduce tumor burden, highlighting its clinical potential.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Since HSP family members may also modulate ferroptosis, further investigation is warranted into their role in GIST ferroptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Ferroptosis has recently emerged as a therapeutic strategy and prognostic marker in GIST.