Ivermectin / mTOR Cancer Research Results

IVM, Ivermectin: Click to Expand ⟱

Features:

Ivermectin — a semisynthetic avermectin-derived macrocyclic lactone and prescription antiparasitic drug, commonly abbreviated IVM and marketed orally as Stromectol. It is formally an anthelmintic/antiparasitic agent derived from avermectins originally isolated from Streptomyces avermitilis. Its established therapeutic action is activation/modulation of invertebrate glutamate-gated chloride channels, producing paralysis and death of susceptible parasites. In oncology, ivermectin is an investigational drug-repurposing candidate rather than an approved anticancer therapy. Preclinical cancer models report multiple effects including PAK1/AKT/mTOR suppression, mitochondrial dysfunction and oxidative stress, WNT-TCF inhibition, Hippo/YAP1 suppression, chloride-dependent cytotoxicity, and immunogenic cell-death/immune modulation.

Primary mechanisms (ranked):

PAK1 degradation with downstream AKT/mTOR suppression and induction of cytostatic/autophagic programs, particularly demonstrated in breast-cancer models.
Mitochondrial dysfunction with ↓ mitochondrial membrane potential, ↓ respiration and ↓ ATP, producing secondary ROS accumulation, oxidative damage and intrinsic apoptosis in several cancer models.
WNT/β-catenin-TCF pathway suppression, reducing WNT-dependent transcription, proliferation, cyclin D1 and cancer-cell growth in responsive models.
Hippo/YAP1 signaling suppression, including ↓ YAP1 expression/nuclear accumulation and ↓ downstream CTGF in susceptible tumor models.
ATP/P2X4/P2X7 signaling modulation and immunogenic cancer-cell death, with increased antitumor T-cell activity and reduced immunosuppressive populations in preclinical breast-cancer models; this provides the rationale for current immune-checkpoint-inhibitor combination trials.
Chloride-channel-associated membrane effects, including chloride-dependent hyperpolarization/cytotoxicity demonstrated in leukemia cells.
Importin α/β-mediated nuclear transport inhibition, potentially affecting transcription factors and other cargo; mechanistically established but tumor relevance varies substantially by model.
JAK/STAT, glycolytic and other metabolic suppression in selected tumor models; these are context-dependent rather than universal ivermectin mechanisms.

Bioavailability / PK relevance: Oral ivermectin is highly lipophilic and poorly water-soluble. After a fasting 12-mg oral dose, reported mean peak plasma concentrations are approximately 31–47 ng/mL at about 4 hours, with a plasma half-life of approximately 18 hours. It is primarily metabolized by CYP3A4 and eliminated predominantly in feces. A high-fat meal can increase systemic bioavailability approximately 2.5-fold. P-glycoprotein-mediated efflux is important in limiting CNS exposure; disruption or inhibition of this protective transport mechanism can increase neurotoxicity risk. Drug interactions and altered hepatic metabolism become particularly important when considering nonstandard high or repeated oncology dosing.

In-vitro vs systemic exposure relevance: A major translational limitation is the exposure gap. Standard antiparasitic dosing produces peak circulating concentrations in the tens of ng/mL, corresponding to only roughly 0.04–0.06 µM, whereas many direct anticancer experiments use approximately 2.5–20 µM or higher ivermectin. Thus, common in-vitro anticancer concentrations can exceed conventional human systemic exposure by tens to several hundred-fold. Some tumor-selective or immune-modulatory effects may occur at lower exposures, and oncology trials are testing repeated dosing, but direct extrapolation of micromolar cell-culture cytotoxicity to standard oral dosing is not justified.

Clinical evidence status: Approved antiparasitic; oncology investigational. The anticancer evidence remains predominantly preclinical, with substantial cell-culture, organoid, xenograft and immunologic evidence but very limited human efficacy data. A Phase I/II study of ivermectin plus pembrolizumab or balstilimab in metastatic triple-negative breast cancer is recruiting, and a separate randomized Phase II ICONIC study is planned to evaluate ivermectin with standard immune-checkpoint inhibition in solid tumors. No completed large randomized controlled trial has established ivermectin as an effective cancer treatment, and it has no FDA or Health Canada oncology indication.

Ivermectin Mechanistic Profile

Rank	Pathway / Axis	Cancer Cells	Normal Cells	Primary Effect	Notes / Interpretation
1	PAK1 / AKT / mTOR	PAK1 ↓ AKT ↓ mTOR ↓ Autophagic flux ↑	↔ / not established	Cytostatic autophagy and reduced proliferation	Strong mechanistic evidence in breast-cancer models; ivermectin promotes ubiquitination-mediated degradation of PAK1 with subsequent suppression of AKT/mTOR signaling.
2	Mitochondrial bioenergetics	Mitochondrial membrane potential ↓ Mitochondrial respiration ↓ ATP ↓	↔ / ↓ (high exposure)	Bioenergetic failure and apoptosis	Demonstrated particularly in renal, colorectal and esophageal cancer models. Preferential effects over corresponding normal cells have been reported in some models but should not be generalized to all tissues.
3	Mitochondrial ROS and oxidative damage	ROS ↑ (dose-dependent)	↔ / ↑ (high exposure)	Oxidative stress and intrinsic apoptosis	ROS is principally a downstream consequence of mitochondrial dysfunction rather than a universal primary molecular target. NAC or mitochondrial metabolic rescue can attenuate ivermectin cytotoxicity in several experimental systems.
4	WNT / β-catenin / TCF	WNT-TCF transcription ↓ β-catenin signaling ↓ CCND1 ↓	↔ / not established	Reduced proliferation and WNT-dependent tumor growth	Well-characterized preclinical repurposing mechanism, particularly relevant to tumors dependent on canonical WNT-TCF signaling.
5	Hippo / YAP1 / CTGF	YAP1 ↓ YAP1 nuclear localization ↓ CTGF ↓ (model-dependent)	↔ / not established	Reduced oncogenic transcription and proliferation	Demonstrated in gastric and other YAP-dependent cancer models. Sensitivity is heterogeneous, and recent organoid work indicates substantial tumor-to-tumor and time-dependent variation.
6	ATP / P2X4 / P2X7 immune signaling	Immunogenic cell death ↑	Antitumor T-cell activity ↑ Immunosuppressive populations ↓ (model-dependent)	Conversion toward an immunologically active tumor microenvironment	Preclinical breast-cancer studies provide the rationale for combining ivermectin with PD-1 pathway inhibition. Human therapeutic benefit remains unproven.
7	Chloride-dependent membrane signaling	Intracellular Cl⁻ ↑ Membrane hyperpolarization ↑ Cell death ↑	Lower effect (model-dependent)	Preferential leukemia-cell cytotoxicity	One of the earliest experimentally demonstrated anticancer mechanisms. Evidence is strongest in leukemia and should not be assumed to be dominant in solid tumors.
8	JAK / STAT signaling	JAK2 ↓ p-STAT3 ↓ p-STAT5 ↓ (model-dependent)	↔ / not established	Reduced survival and metabolic signaling	Demonstrated in selected models including glioma; not established as a universal ivermectin target across cancer types.
9	Glycolytic metabolism	GLUT4 ↓ HK2 ↓ PFK1 ↓ Pyruvate ↓ ATP ↓ (model-dependent)	↔ / ↓ (high concentration only)	Reduced glycolytic capacity and enhanced metabolic stress	Strongly demonstrated in particular glioma models through GLUT4/JAK/STAT signaling, but insufficient evidence supports treating glycolysis as a universal primary ivermectin mechanism.
10	Intrinsic apoptosis	Bax ↑ Bcl-2 ↓ Caspase activity ↑ PARP cleavage ↑	↔ / ↑ (high exposure)	Programmed tumor-cell death	Common downstream phenotype following mitochondrial dysfunction, ROS accumulation and signaling disruption.
11	Importin α / β nuclear transport	Importin-dependent nuclear transport ↓	↓ (exposure-dependent)	Reduced nuclear localization of susceptible cargo	Biochemically important ivermectin activity, but it is not cancer-cell-specific and its contribution to antitumor effects varies by substrate and tumor context.
12	HIF hypoxia signaling	HIF-1α nuclear localization ↓ HIF transcription ↓ (model-dependent)	↓ (context-dependent)	Reduced cellular hypoxia-response transcription	Likely linked partly to importin α/β inhibition. Relevant in hypoxic models but not sufficiently universal to rank as a core ivermectin anticancer mechanism.
13	Cancer stemness and invasion	Stemness ↓ Migration ↓ Invasion ↓ (model-dependent)	↔ / not established	Reduced aggressive tumor phenotype	Reported across several preclinical systems and probably reflects convergence of WNT, YAP, AKT and related pathways rather than a single direct target.
14	NRF2 antioxidant response	↔ / context-dependent	↔ / context-dependent	Not established as a core ivermectin mechanism	Evidence is insufficient to assign a consistent ivermectin-induced NRF2 direction across cancers. It should not currently be presented as a standard ivermectin pathway.
15	Clinical Translation Constraint	Effective experimental exposure often exceeds standard human exposure	Neurotoxicity and systemic toxicity risk ↑ with excessive exposure	Limits translation of direct in-vitro cytotoxicity	Standard oral dosing produces approximately 0.04–0.06 µM peak plasma concentrations, whereas many cancer-cell experiments use several µM. CYP3A4 metabolism, food-dependent exposure, P-glycoprotein-mediated CNS protection, concomitant drugs and repeated high dosing are important clinical constraints. Current oncology studies are investigational and efficacy remains unconfirmed.

mTOR, mammalian target of rapamycin: Click to Expand ⟱

Source: HalifaxProj (inhibit)

Type:

mTOR (mechanistic target of rapamycin) is a central regulator of cell growth, proliferation, metabolism, and survival. It is a serine/threonine kinase that integrates signals from nutrients, growth factors, and cellular energy status.
mTOR promotes protein synthesis and cell growth by activating downstream targets such as S6 kinase and 4E-BP1. In cancer, this pathway can become hyperactivated, leading to uncontrolled cell proliferation.

mTor Inhibitors:
-rapamycin (Sirolimus): classic natural product mTOR inhibitor
-Curcumin
-Resveratrol
-Epigallocatechin Gallate (EGCG)
-Honokiol

Scientific Papers found: Click to Expand⟱

8038-

IVM,

Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction

in-vitro,

PC,

*AntiP↑, Ivermectin, an antiparasitic drug, exerts antitumor effects in various cancer types.
AntiTum↑,
ChemoSen↑, ivermectin–gemcitabine combination treatment suppressed pancreatic cancer more effectively than gemcitabine alone treatment.
TumCP↓, ivermectin–gemcitabine combination inhibited cell proliferation via G1 arrest of the cell cycle, as evidenced by the downregulation of cyclin D1 expression and the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcriptio
TumCCA↑,
cycD1/CCND1↓,
mTOR↓,
STAT3↑, and activator of transcription 3 (STAT-3) signaling pathway.
Apoptosis↑, Ivermectin–gemcitabine increased cell apoptosis by inducing mitochondrial dysfunction via the overproduction of reactive oxygen species and decreased the mitochondrial membrane potential.
mtDam↑,
ROS↑,
MMP↓,
OCR↓, combination treatment also decreased the oxygen consumption rate and inhibited mitophagy, which is important for cancer cell death.
MitoP↓,

8039-

IVM,

Ivermectin-Induced Apoptotic Cell Death in Human SH-SY5Y Cells Involves the Activation of Oxidative Stress and Mitochondrial Pathway and Akt/mTOR-Pathway-Mediated Autophagy

in-vitro,

neuroblastoma,

SH-SY5Y

*toxicity↑, Ivermectin (IVM) could cause potential neurotoxicity; however, the precise molecular mechanisms remain unclear.
TumCD↑, The results show that IVM treatment (2.5–15 μM) for 24 h could induce dose-dependent cell death in SH-SY5Y cells.
ROS↑, Compared to the control, IVM treatment significantly promoted the production of ROS, mitochondrial dysfunction, and cell apoptosis.
mtDam↑,
Apoptosis↑,
MitoP↑, IVM treatment also promoted mitophagy and autophagy, which were charactered by the decreased expression of phosphorylation (p)-Akt and p-mTOR proteins, increased expression of LC3II, Beclin1, ATG5, PINK, and Pakin1 proteins and autophagosome formatio
TumAuto↑,
p‑Akt↓,
p‑mTOR↓,
LC3II↑,
Beclin-1/ATG6↑,
ATG5↑,
PINK1↑,
PARK2↑,
tumCV↓, At 6 h and 12 h, IVM treatment at 15 μM significantly decreased the cell viabilities to 44.3% and 35.6% (both p < 0.01), respectively;
MDA↑, IVM treatment at the doses of 10 and 15 μM significantly increased the levels of MDA to 0.25 nmol/mg and 0.76 nmol/mg protein (both p < 0.01) (Figure 3B), respectively; increased the activities of SOD to 1.61 U/mg and 3.48 U/mg protein (both p < 0.
SOD↑,
Catalase↑,
eff↓, NAC treatment at 10 mM significantly inhibited the IVM-induced production of ROS
MMP↓, IVM treatment significantly decreased the ΔΨm in a dose-dependent manner.
BAX↑, IVM treatment significantly increased the expressions of Bax, cleaved caspase-3, cleaved caspase-9, cleaved PARP-1 proteins, and CytC proteins, and decreased the expressions of Bcl-2 and pro-caspase-3 proteins.
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
Cyt‑c↑,
Bcl-2↓,
proCasp3↓,
Bax:Bcl2↑, IVM treatment at 10 μM significantly increased the ratio of Bax/Bcl-2 to 2.6-fold
eff↑, Inhibition of Autophagy Improves Ivermectin-Induced Cytotoxicity, Oxidative Stress, and Apoptotic Cell Death
*AntiP↑, IVM has been widely used as an antiparasitic drug in human and veterinary medicines
*Inflam↓, IVM exhibited several new threptic effects, including anti-cancer, anti-inflammation, anti-diabetic, and antiviral effects
*AntiDiabetic↑,
*AntiViral↑,
BBB∅, In relation to the current recommended dose, IVM is not thought to readily cross the blood–brain barrier in humans
toxicity↝, It has been reported that an IVM overdose could induce neurotoxicity in SARS-CoV-2 patients and the main neurotoxic symptoms include confusion, ataxia, weakness, hypotension, and seizures

8040-

IVM,

Ivermectin, a potential anticancer drug derived from an antiparasitic drug

Review,

Var,

Akt↓, inhibition by IVM of the Akt/mTOR pathway to induce autophagy and p-21-activated kinase 1(PAK1)was the target of IVM for breast cancer
mTOR↓,
TumAuto↑,
TumCP↓, IVM could inhibit the proliferation of the canine breast tumor cell lines CMT7364 and CIPp by blocking the cell cycle without increasing apoptosis, and the mechanism of IVM may be related to the inhibition of the Wnt pathway
TumCCA↑,
Wnt↓,
YAP/TEAD↓,
MMP↓, IVM could significantly reduce the mitochondrial membrane potential and inhibit mitochondrial respiration and ATP production.
mitResp↓,
ATP↓,
eff↓, acetyl-L-cysteine (NAC), could reverse IVM-induced inhibition
eff↑, it was found that IVM could enhance the drug activity of the anti-androgen drug enzalutamide in the prostate cancer cell line LNCaP and reverse the resistance of the prostate cancer cell line PC3 to docetaxel
ROS↑, induction of reactive oxygen species (ROS) production.
ChemoSen↑, IVM can enhance the efficacy of cisplatin to improve the treatment of epithelial ovarian cancer, and the mechanism is related to the inhibition of the Akt/mTOR pathway
PAK1↓, IVM also had a cytotoxic effect on a variety of nasopharyngeal cancer cells in vitro, and the mechanism is related to the reduction of PAK1 kinase activity to inhibit the MAPK pathway.
MAPK↓,
EMT↓, IVM could reduce the metastasis of lung cancer cells by inhibiting EMT.
Beclin-1/ATG6↑, IVM in the breast cancer cell lines MCF-7 and MDA-MB-231 significantly increased intracellular autophagic flux and the expression of key autophagy proteins such as LC3, Bclin1, Atg5
ATG5↑,
CSCs↓, Further studies showed that IVM could inhibit CSCs by regulating the PAK1-STAT3 axis
STAT3↝,
P-gp/ABCB1↓, Several studies have confirmed that IVM could reverse drug resistance by inhibiting P-gp and MDR-associated proteins
MDR1↓,
HSP27↓, Inhibit HSP27 Prostate cancer, Lung cancer Colorectal cancer
Chl↑, Activate chloride channels Leukemia
TFE3↑, Increase TFE3 Activity Melanoma

8047-

IVM,

The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug

Review,

Var,

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.

8049-

IVM,

Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer

vitro+vivo,

BC,

breast cancer xenografts

*AntiP↑, Ivermectin, a broad-spectrum antiparasitic drug, has recently been characterized as a potential anticancer agent due to observed antitumor effects.
AntiCan↑,
AntiTum↑,
PAK1↓, decreased P21-activated kinase 1 (PAK1) expression via the ubiquitination-mediated degradation pathway.
p‑Akt↓, decreases the phosphorylation level of Akt, resulting in the blockade of the Akt/mTOR signaling pathway.
Akt↓,
mTOR↓,
TumCG↓, In breast cancer xenografts, the ivermectin-induced cytostatic autophagy leads to suppression of tumor growth.

1168-

IVM,

SRF,

Ivermectin synergizes sorafenib in hepatocellular carcinoma via targeting multiple oncogenic pathways

in-vitro,

HCC,

TumMeta↓,
mTOR↓,
EMT↓,
CSCsMark↓,
STAT3↓,

8020-

IVM,

Ivermectin induces PAK1-mediated cytostatic autophagy in breast cancer

vitro+vivo,

BC,

AntiP↑, Ivermectin is a broad-spectrum antiparasitic drug that has recently been demonstrated to exhibit potent anticancer activity against colon cancer, ovarian cancer, melanoma and leukemia.
TumAuto↑, We recently found that ivermectin markedly inhibits the growth of breast cancer cells by stimulating cytostatic macroautophagy/autophagy in vitro and in vivo.
Akt↓, inhibits the AKT-MTOR signaling pathway by promoting ubiquitination-mediated degradation of PAK1 (p21 [RAC1] activated kinase 1), leading to increased autophagic flux.
mTOR↓,
PAK1↓,
selectivity↑, marked growth inhibition after 24-h treatment with ivermectin in a range of breast cancer cell lines, with no obvious effects on nontumorigenic human breast cells.

8027-

IVM,

Progress in Understanding the Molecular Mechanisms Underlying the Antitumour Effects of Ivermectin

Review,

Var,

*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%.

8028-

IVM,

Ivermectin as an Alternative Anticancer Agent: A Review of Its Chemical Properties and Therapeutic Potential

Review,

Var,

*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.

8029-

IVM,

Ivermectin in Cancer Treatment: Should Healthcare Providers Caution or Explore Its Therapeutic Potential?

Review,

Var,

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
Synergy↑, 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.

8031-

IVM,

Antiparasitic agents in oncology: Innovative mechanisms, emerging evidence and clinical potential in cancer treatment

Review,

Nor,

*AntiP↑, Drugs originally developed to treat parasitic infections, including ivermectin, mebendazole, niclosamide, albendazole, artesunate, flubendazole, and other antiparasitic agents, have demonstrated compelling anticancer properties across a wide range of
Wnt↓, inhibition of key oncogenic pathways (including Wnt/β-catenin, PI3K/Akt/mTOR, and Hedgehog signaling), immunomodulation, and targeting cancer stem cell populations.
β-catenin/ZEB1↓,
PI3K↓,
Akt↓,
mTOR↓,
HH↓,
Imm↑, immunostimulatory properties
CSCs↓,
P-gp/ABCB1↓, modulation of the P-glycoprotein drug efflux pump, activation of chloride ion channels, and inhibition of oncogenic signaling.
Chl↓,
angioG↓, demonstrated anti-angiogenic

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome(tgid=24) ⓘ

AntiP↑, 1,
Total Targets: 102

Pathway results for Effect on Normal Cells:

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↝, 1,

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↑, 1, toxicity↑, 1,

Infection & Microbiome(tgid=24) ⓘ

AntiP↑, 6, AntiViral↑, 1,
Total Targets: 6

Scientific Paper Hit Count for: mTOR, mammalian target of rapamycin

11 Ivermectin
1 Sorafenib (brand name Nexavar)

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#:10  Target#:209  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

Ivermectin / mTOR Cancer Research Results

Ivermectin Mechanistic Profile

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Pathway results for Effect on Normal Cells:

Immune & Inflammatory Signaling(tgid=16) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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