ICD Cancer Research Results

ICD, immunogenic cell death (ICD): Click to Expand ⟱
Source:
Type: type of cell death
Immunogenic cell death (ICD) is a form of regulated cell death that stimulates the immune system against dying cells.
ICD is characterized by the release or exposure of specific damage‐associated molecular patterns (DAMPs) that function as “danger signals.” Key DAMPs (or ICD markers) include:
• Calreticulin (CRT) exposure
• ATP release
• High mobility group box 1 protein (HMGB1) release
• Heat shock proteins (such as HSP70 and HSP90)
• Type I interferon (IFN) responses (indirectly involved through downstream signaling)

Higher expression/exposure of ICD markers such as calreticulin, ATP, extracellular HMGB1 (with favorable redox states), HSP70/90 when released, and type I IFN responses are generally associated with enhanced antitumor immunity and improved prognosis in several cancer types.
Scientific Papers found: Click to Expand⟱
1360- Ash,  immuno,    Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer
- in-vitro, Lung, H1650 - in-vitro, Lung, A549 - in-vitro, CRC, HCT116 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
PD-L1↑,
eff↓, The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process.
ROS↑,
ER Stress↑,
Apoptosis↑,
BAX↑,
Bak↑,
BAD↑,
Bcl-2↓,
XIAP↓,
survivin↓,
cl‑PARP↑,
CHOP/DDIT3↑,
p‑eIF2α↑, phosphorylation of the eukaryotic initiation factor eIF-2
ICD↑,
eff↑, WFA Sensitizes LLC Syngeneic Mouse Tumors to α-PD-L1 In Vivo

1376- BBR,  immuno,    Berberine sensitizes immune checkpoint blockade therapy in melanoma by NQO1 inhibition and ROS activation
- in-vivo, Melanoma, NA
OS↑, BBR could sensitize ICB to inhibit tumor growth and increased the survival rate of mice.
ROS↑,
NQO1↓,
ICD↑,

7970- BUL,    Bullatacin triggers immunogenic cell death of colon cancer cells by activating endoplasmic reticulum chaperones
- in-vitro, Colon, SW480 - in-vitro, Colon, HT-29
Apoptosis↑, bullatacin induced apoptosis in both SW480 cells and HT-29 cells in a time-dependent manner at 10 nM, as assessed by flow cytometry
ICD↑, CRT and HSP90 (biomarkers of early ICD) significantly accumulated on the cell membrane surface after approximately 6 h of treatment with bullatacin.
e-CRT↑,
e-HSP90↑,
ER Stress↑, bullatacin triggered ICD via activation of the endoplasmic reticulum stress (ERS) signalling pathway.
e-HMGB1↑, Bullatacin promotes the release of HMGB1, HSP90 and HSP70 in late apoptotic cells
e-HSP70/HSPA5↑,
e-HSP90↑,
CHOP/DDIT3↑, 10 nM bullatacin significantly upregulated the mRNA expression of calnexin and CHOP in two colon cancer cell lines
eff↑, which may be excellent strategies enhancing tumour immunogenicity can be applied to improve the efficacy of cancer immunotherapy.

1601- Cu,    The copper (II) complex of salicylate phenanthroline induces immunogenic cell death of colorectal cancer cells through inducing endoplasmic reticulum stress
- in-vitro, CRC, NA
i-CRT↓, Cu(sal)phen induced the release of calreticulin (CRT), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1), the main molecular markers of ICD (immunogenic cell death)
ICD↑,
i-ATP↓,
i-HMGB1↓,
ER Stress↑, accumulation of ROS and inducing ERS
ROS↑,
DCells↑, promoted the maturation of dendritic cells (DCs)
CD8+↑, and activation of CD8+T cells
IL12↑, secretion of interleukin-12 (IL-12) and interferon-γ (IFN-γ)
IFN-γ↑,
TGF-β↓, while downregulating transforming growth factor-β (TGF-β) levels

5010- DSF,  Cu,  Rad,    Disulfiram/Copper Combined with Irradiation Induces Immunogenic Cell Death in Melanoma
- in-vivo, Melanoma, B16-F10
Apoptosis↑, DSF/Cu + IR significantly increased the cellular apoptosis and increased ICD markers:
ICD↑,
HMGB1↑, high-mobility group box 1 (HMGB1) release, and decreased intracellular ATP levels. I
ATP↓,
TumCG↓, DSF/Cu combined with IR treatment inhibited tumor growth and enhanced tumor-infiltrating immune cells in the B16F10-bearing C57BL/6 model

8029- IVM,    Ivermectin in Cancer Treatment: Should Healthcare Providers Caution or Explore Its Therapeutic Potential?
- Review, Var, NA
TumCP↓, Ivermectin's anticancer effects, including inhibition of cancer cell proliferation, induction of apoptosis, and modulation of signaling pathways (e.g., Wnt/β-catenin, Akt/mTOR) across various cancers.
Apoptosis↑,
Wnt↓,
β-catenin/ZEB1↓,
Akt↓, Ivermectin inhibited the Akt/mTOR pathway, a key regulator of tumor growth and metabolism
mTOR↓,
BBB∅, exhibiting minimal toxicity to humans due to poor penetration of the blood–brain barrier
ROS↑, In colorectal cancer, it induces reactive oxygen species (ROS)-mediated mitochondrial apoptosis by disrupting mitochondrial membrane potential, activating caspases (e.g., caspase-3/9
MMP↓,
Casp3↓,
Casp9↑,
TumCCA↑, Ivermectin induced caspase-dependent apoptosis and G0/G1-phase cell cycle arrest, partly through increased p53 expression in cells with wild-type p53, promoting cell death
P53↑,
cMyc↓, downstream genes like c-Myc and MMP-9 [
MMP9↓,
HSP27↓, inhibits HSP27, which is synergistically lethal to cells with oncogenic activation of EGFR o
ICD↑, induces immunogenic cancer cell death (ICD) and robust T-cell infiltration
eff↑, synergizes with anti-PD1 antibody to control tumor growth and induce protective immunity
*AntiP↑, Ivermectin has become a cornerstone therapy for treating human parasitic diseases like onchocerciasis and strongyloidiasis.

8028- IVM,    Ivermectin as an Alternative Anticancer Agent: A Review of Its Chemical Properties and Therapeutic Potential
- Review, Var, NA
*BioAv↝, IVM’s distinct physicochemical profile, including high lipophilicity, poor aqueous solubility, and moderate acid stability, which collectively affect its bioavailability and pharmacokinetic behavior.
Apoptosis↑, induction of apoptosis, inhibition of tumor cell proliferation, and modulation of the tumor microenvironment across a range of malignancies.
TumCP↓,
Wnt↓, IVM inhibits the Wnt/β-catenin signaling pathway in gastric cancer cells, leading to suppressed tumor growth and metastasis.
β-catenin/ZEB1↓,
TumCG↓,
TumMeta↓,
PI3K↓, IVM disrupts the PI3K/AKT/mTOR pathway in pancreatic cancer, resulting in increased apoptosis and reduced cell proliferation.
Akt↓,
mTOR↓,
TumPF↓,
CSCs↓, IVM selectively suppresses CSCs in breast cancer models and downregulates genes associated with cellular stemness,
eff↑, combining IVM with immune checkpoint inhibitors, such as anti-PD1 antibodies, enhances antitumor immune responses and induces complete tumor regression in breast cancer models.
ChemoSen↑, Combination of Paclitaxel + Ivermectin or Paclitaxel + Pitavastatin produced maximum cytotoxicity and strong synergy in both chemoresistant lines, surpassing the effect of each drug alone
mtDam↑, IVM induces mitochondrial dysfunction (↓ψm, ↓ATP) with ↑ROS, inhibits NF-κB (↓p-p65), increases Bax/Bcl-2 and activates caspases 9/3
MMP↓,
ATP↓,
ROS↑,
NF-kB↓,
BAX↑,
Casp3↑,
Casp9↑,
ICD↑, induces immunogenic cell death
Ki-67↓, ↓Ki67, PSA
PSA↓,
YAP/TEAD↓, interferes with multiple oncogenic pathways, including WNT/TGF-β, PAK1/STAT3, YAP1, Akt/mTOR, and Wnt/β-catenin.

8027- IVM,    Progress in Understanding the Molecular Mechanisms Underlying the Antitumour Effects of Ivermectin
- Review, Var, NA
*AntiP↑, Ivermectin was soon adopted in 1987 as a human medicine that was originally used for the treatment of onchocerciasis, a parasitic infection.
TumCD↑, Ivermectin causes cell death in cancer cell lines by inducing PAK1-mediated cytostatic autophagy,
PAK1↑,
TumAuto↑,
Casp↑, caspase-dependent apoptosis and immunogenic cell death (ICD) through the modulation of some pathways, including the WNT-T cell factor (TCF), Hippo and Akt/mTOR pathways.
ICD↑,
TCF↝, Ivermectin Serves as a WNT-T Cell Factor (TCF) Pathway Response Blocker
Hippo↓,
Akt↓, Ivermectin inhibits the Akt/mTOR signalling pathway by increasing the ubiquitination-mediated degradation of PAK1,
mTOR↓,
angioG↓, In addition, ivermectin induces the multidrug resistance protein (MDR), has potent anti-mitotic activity, targets angiogenesis and inhibits cancer stem-like cells (CSCs).
CSCs↓, Ivermectin Is an Inhibitor of CSCs
MMP↓, collapse of the mitochondrial membrane potential (ΔΨm) and the release of cytochrome c,
Cyt‑c↑,
Apoptosis↑, ivermectin induces apoptosis in glioblastoma and HeLa cells by enhancing cytochrome c release, upregulating Bax and p53 expression, downregulating Bcl-2 expression and decreasing the levels of cyclin E, cyclin D1, CDK2, CDK6 and CDK4
BAX↑,
P53↑,
Bcl-2↓,
cycE/CCNE↓,
cycD1/CCND1↓,
CDK2↓,
CDK6↓,
CDK4↓,
YAP/TEAD↓, Ivermectin Inhibits Proliferation by Inhibiting Yea-Associated Protein 1 (YAP1)
TFE3↑, Ivermectin treatment increases TFE3(Ser321) dephosphorylation, activates TFE3 nuclear translocation and stimulates activation of the TFE3 reporter in human melanoma cells
mTORC1↓, Ivermectin treatment also clearly decreases phosphorylation of the mTORC1 substrate p-70S6K, which results in induction of mTORC1 deactivation.
mitResp↓, Ivermectin Inhibits Mitochondrial Respiration
OCR↓, inhibitory effect of ivermectin on the basal oxygen consumption rate (OCR) and maximum OCR in U87, T98G
compI↓, ivermectin inhibits mitochondrial respiration by decreasing the activity of respiratory complex I enzyme
MMP↓, ivermectin decreased the mitochondrial membrane potential,
ROS↑, Consistently, obviously increased levels of ROS and mitochondrial superoxide as well as decreased ATP levels were also found in glioblastoma, HBMECs and chronic myeloid leukaemia (CML) cells treated with ivermectin
SOD2↑,
ATP↓,
eff↓, (ALCAR, a mitochondrial fuel) and N-acetyl-l-cysteine (NAC, an antioxidant) reversed the inhibitory effects of ivermectin in renal cell carcinoma (RCC) cells, which indicates that mitochondria are the target of ivermectin.
mitA↓, Ivermectin Exerts Anti-Mitotic Activity
P-gp/ABCB1↓, Ivermectin Is a P-Glycoprotein (P-Gp) Inhibitor
TumVol↓, After 10 to 42 days, treatment with ivermectin can reduced the tumour volume by more than 50%.

8026- IVM,  immuno,    Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer
- vitro+vivo, BC, 4T1
ICD↑, FDA-approved anti-parasitic drug ivermectin induces immunogenic cancer cell death (ICD) and robust T cell infiltration into breast tumors.
Imm↝, ivermectin also selectively targets immunosuppressive populations including myeloid cells and Tregs, resulting in enhanced Teff/Tregs ratio
eff↑, While neither agent alone showed efficacy in vivo, combination therapy with ivermectin and checkpoint inhibitor anti-PD1 antibody achieved synergy in limiting tumor growth (p = 0.03) and promoted complete responses
TumVol↓, Mean tumor volume over time was significantly decreased by the ivermectin and anti-PD1 antibody combination relative to no treatment

8047- IVM,    The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug
- Review, Var, NA
Half-Life↝, it has a mean peak plasma level of ~4 h after oral administration with a second peak at 6-12 h because of enterohepatic recycling. its half-life is approximately 19 h
MDR1↓, Ivermectin as an inhibitor of the multi-drug resistance (MDR) phenotype
P-gp/ABCB1↓, concluding that ivermectin is also a substrate and an inhibitor of P-glycoprotein
mtDam↑, Ivermectin as an inductor of mitochondrial dysfunction and oxidative damage
ROS↑,
OCR↓, ivermectin inhibits in a dose-dependent manner the basal and maximum oxygen consumption rate (OCR), most likely by decreasing the enzyme activity of respiratory complex I but not II, IV or V,
compI↓,
MMP↓, both the membrane potential and electrochemical proton gradient decrease while a significant increase in mitochondrial superoxide and decreased ATP are observed.
mt-SOD↑,
ATP↓,
p‑Akt↓, Results showed that ivermectin decreases phosphorylation of Akt (S473), mTOR (S2481)
p‑mTOR↓,
eff↓, abolition of the inhibitory effect of ivermectin in these renal cancer cell lines when co-treated with acetyl-L-carnitine (ALCAR) or N-acetyl-L-cysteine (NAC)
ICD↑, Ivermectin as an inductor of immunogenic cell death (ICD)
TumAuto↑, Ivermectin as an inductor of autophagy
PAK1↓, Ivermectin in ovarian and glioblastoma cancer cell lines promotes ubiquitination-mediated degradation of the oncogenic kinase PAK1
Wnt↓, Ivermectin as an inhibitor of the WNT-TCF pathway
TCF↓,
Nanog↓, 0.5 µM it reduces NANOG and SOX2 gene expression by 80%,
SOX2↓,
CSCs↓, Ivermectin as a stem-cell cancer inhibitor
CD44↓, ivermectin preferentially inhibits the viability of CSCs-enriched populations (CD44+/CD24-) and cells growing in spheroids,
CD24↓,
Dose↝, Thus, the in vitro and in vivo results with ivermectin strongly suggest that its antitumor effects in cancer patients can be achieved at feasible doses.


Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

TFE3↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

compI↓, 2,   ICD↑, 10,   NQO1↓, 1,   ROS↑, 7,   mt-SOD↑, 1,   SOD2↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 4,   i-ATP↓, 1,   mitResp↓, 1,   MMP↓, 5,   mtDam↑, 2,   OCR↓, 2,   XIAP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

cMyc↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 3,   p‑Akt↓, 1,   Apoptosis↑, 6,   BAD↑, 1,   Bak↑, 1,   BAX↑, 3,   Bcl-2↓, 2,   Casp↑, 1,   Casp3↓, 1,   Casp3↑, 1,   Casp9↑, 2,   Cyt‑c↑, 1,   Hippo↓, 1,   survivin↓, 1,   TumCD↑, 1,   YAP/TEAD↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 2,   e-CRT↑, 1,   i-CRT↓, 1,   p‑eIF2α↑, 1,   ER Stress↑, 3,   HSP27↓, 1,   e-HSP70/HSPA5↑, 1,   e-HSP90↑, 2,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 2,   cl‑PARP↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   mitA↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CD24↓, 1,   CD44↓, 1,   CSCs↓, 3,   mTOR↓, 3,   p‑mTOR↓, 1,   mTORC1↓, 1,   Nanog↓, 1,   PI3K↓, 1,   SOX2↓, 1,   TCF↓, 1,   TCF↝, 1,   TumCG↓, 2,   Wnt↓, 3,  

Migration(tgid=13) ⓘ

Ki-67↓, 1,   MMP9↓, 1,   PAK1↓, 1,   PAK1↑, 1,   TGF-β↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   TumPF↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB∅, 1,   P-gp/ABCB1↓, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

DCells↑, 1,   HMGB1↑, 1,   e-HMGB1↑, 1,   i-HMGB1↓, 1,   IFN-γ↑, 1,   IL12↑, 1,   Imm↝, 1,   NF-kB↓, 1,   PD-L1↑, 1,   PSA↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   Dose↝, 1,   eff↓, 3,   eff↑, 5,   Half-Life↝, 1,   MDR1↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

Ki-67↓, 1,   PD-L1↑, 1,   PSA↓, 1,  

Functional Outcomes(tgid=23) ⓘ

OS↑, 1,   TumVol↓, 2,  

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 1,  
Total Targets: 96

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiP↑, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↝, 1,  
Total Targets: 2

Scientific Paper Hit Count for: ICD, immunogenic cell death (ICD)
5 Ivermectin
3 immunotherapy
2 Copper and Cu NanoParticles
1 Ashwagandha(Withaferin A)
1 Berberine
1 Bullatacin
1 Disulfiram
1 Radiotherapy/Radiation
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:1080  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

Home Page