Ivermectin / EMT Cancer Research Results

IVM, Ivermectin: Click to Expand ⟱

Features:

Ivermectin , Medicationthat treats some parasitic diseases

Ivermectin (IVM; brands include Stromectol; Rx antiparasitic) — a macrocyclic lactone anthelmintic used for certain parasitic infections. Oncology relevance is primarily repurposing research (preclinical + early trials), not an approved anticancer indication.

Primary mechanisms (conceptual rank):
1) Parasite MoA: glutamate-gated Cl⁻ channel modulation → paralysis/death (invertebrate-selective)
2) Repurposing (cancer): multi-pathway inhibition (Wnt/β-catenin ↓; STAT3 ↓; PI3K/AKT/mTOR ↓; PAK1-linked signaling ↓; model-dependent)
3) Tumor cell stress programs (autophagy/apoptosis ↑; context-dependent)
4) Tumor microenvironment/immune modulation (context-dependent; exploratory)

Bioavailability / PK relevance: Oral; half-life ~18 h; primarily CYP3A4 metabolism; excretion mainly fecal. High-fat meal can increase bioavailability (~2.5× reported in product monograph). CNS exposure is normally limited by P-glycoprotein at the BBB (risk increases if P-gp function is impaired or inhibited).

In-vitro vs oral exposure: Many reported anticancer effects use concentrations that may exceed typical systemic exposure from standard antiparasitic dosing (high concentration only for direct tumor cytotoxicity in many models).

Clinical evidence status: Approved antiparasitic; oncology evidence = preclinical + small/early human studies (no oncology RCT approval/indication).

Ivermectin — Cancer vs Normal Cell Pathway Map

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	Wnt/β-catenin	↓ (model-dependent)	↔	R/G	Reduced proliferation / stemness programs	Frequently cited repurposing axis; relevance highest in Wnt-dependent contexts.
2	STAT3	↓ (model-dependent)	↔	R/G	Anti-survival transcription blockade	Often presented as a central anti-tumor signaling node in repurposing literature.
3	PI3K/AKT/mTOR	↓ (model-dependent)	↔	R/G	Reduced anabolic survival signaling	Commonly co-reported with Wnt/STAT3 effects; may contribute to cytostatic phenotypes.
4	PAK1-linked signaling	↓ (model-dependent)	↔	R/G	Reduced migration / growth signaling	Repurposing reviews highlight PAK1 as a putative node; tumor-type dependence is high.
5	Autophagy	↑ or ↔ (context-dependent)	↔ / ↑ (stress-dependent)	R/G	Stress adaptation vs growth suppression	Often cytostatic; can support survival or contribute to death depending on context.
6	Glycolysis / Warburg (glucose uptake, lactate output)	↓ (model-dependent; secondary to energy stress; high concentration only)	↔ / ↓ (high concentration only)	R/G	Reduced glycolytic flux / lactate production	Often downstream of mitochondrial ATP stress and PI3K/AKT/mTOR inhibition; not a uniformly demonstrated primary ivermectin target and typically requires higher experimental exposure.
7	Apoptosis (intrinsic; caspases)	↑ (model-dependent; high concentration only)	↔ / ↑ (high exposure)	R/G	Programmed cell death	Typically downstream of pathway inhibition/stress; exposure gap common.
8	ROS	↑ or ↔ (context-dependent)	↔	P/R	Secondary stress contributor	Not a canonical primary target; can emerge downstream of stress signaling.
9	NRF2 (protective vs resistance role)	↔ / ↑ (adaptive; context-dependent)	↔ / ↑ (adaptive)	R/G	Stress-response adjustment	Secondary; could blunt efficacy if antioxidant adaptation dominates.
10	HIF-1α	↔ / ↓ (model-dependent)	↔	G	Not a consistent primary axis	Reported variably; treat as secondary unless tumor model is hypoxia-driven.
11	Ferroptosis	↔ (insufficiently established)	↔	R/G	Not canonical	Not a standard ivermectin-first claim; include only with specific supporting studies.
12	Ca²⁺ signaling	↔	↔	P/R	No primary role	Include only if a model explicitly measures Ca²⁺/ER-stress endpoints.
13	Clinical Translation Constraint	↓ (constraint)	↓ (constraint)	—	Exposure + evidence + BBB safety context	Most tumor-directed effects are preclinical and often high-concentration. PK/food effects (high-fat meal ↑ exposure), CYP3A4 metabolism, and P-gp BBB protection (neurotoxicity risk if impaired/inhibited) are key constraints; oncology trials remain early.

TSF legend:
P: 0–30 min (primary/rapid effects)
R: 30 min–3 hr (acute signaling/stress response)
G: >3 hr (gene-regulatory/phenotype outcomes)

EMT, Epithelial-Mesenchymal Transition: Click to Expand ⟱

Source:

Type:

Biological process in which epithelial cells lose their cell polarity and cell-cell adhesion properties and gain mesenchymal traits, such as increased motility and invasiveness. This process is pivotal during embryogenesis and wound healing. Hh signaling pathway is able to regulate the EMT. Snail, E-cadherin and N-cadherin, key components of EMT; EMT-related factors, E-cadherin, N-cadherin, vimentin; The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin.
EMT is regulated by various signaling pathways, including TGF-β, Wnt, Notch, and Hedgehog pathways. Transcription factors such as Snail, Slug, Twist, and ZEB play critical roles in repressing epithelial markers (like E-cadherin) and promoting mesenchymal markers (like N-cadherin and vimentin).
EMT is associated with increased tumor aggressiveness, enhanced migratory and invasive capabilities, and resistance to apoptosis.

Scientific Papers found: Click to Expand⟱

1168-

IVM,

SRF,

Ivermectin synergizes sorafenib in hepatocellular carcinoma via targeting multiple oncogenic pathways

in-vitro,

HCC,

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

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:

Proliferation, Differentiation & Cell State ⓘ

CSCsMark↓, 1, EMT↓, 1, mTOR↓, 1, STAT3↓, 1,

Migration ⓘ

TumMeta↓, 1,
Total Targets: 5

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: EMT, Epithelial-Mesenchymal Transition

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