Ivermectin / mTOR 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)

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⟱

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: mTOR, mammalian target of rapamycin

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