Ivermectin / cycD1/CCND1 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

RankPathway / AxisCancer CellsNormal CellsTSFPrimary EffectNotes / Interpretation
1Wnt/β-catenin ↓ (model-dependent)↔R/G Reduced proliferation / stemness programs Frequently cited repurposing axis; relevance highest in Wnt-dependent contexts.
2STAT3 ↓ (model-dependent)↔R/G Anti-survival transcription blockade Often presented as a central anti-tumor signaling node in repurposing literature.
3PI3K/AKT/mTOR ↓ (model-dependent)↔R/G Reduced anabolic survival signaling Commonly co-reported with Wnt/STAT3 effects; may contribute to cytostatic phenotypes.
4PAK1-linked signaling ↓ (model-dependent)↔R/G Reduced migration / growth signaling Repurposing reviews highlight PAK1 as a putative node; tumor-type dependence is high.
5Autophagy ↑ 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.
7Apoptosis (intrinsic; caspases) ↑ (model-dependent; high concentration only)↔ / ↑ (high exposure)R/G Programmed cell death Typically downstream of pathway inhibition/stress; exposure gap common.
8ROS ↑ or ↔ (context-dependent)↔P/R Secondary stress contributor Not a canonical primary target; can emerge downstream of stress signaling.
9NRF2 (protective vs resistance role) ↔ / ↑ (adaptive; context-dependent)↔ / ↑ (adaptive)R/G Stress-response adjustment Secondary; could blunt efficacy if antioxidant adaptation dominates.
10HIF-1α ↔ / ↓ (model-dependent)↔G Not a consistent primary axis Reported variably; treat as secondary unless tumor model is hypoxia-driven.
11Ferroptosis ↔ (insufficiently established)↔R/G Not canonical Not a standard ivermectin-first claim; include only with specific supporting studies.
12Ca²⁺ signaling ↔↔P/R No primary role Include only if a model explicitly measures Ca²⁺/ER-stress endpoints.
13Clinical 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)
cycD1/CCND1, cyclin D1 pathway: Click to Expand ⟱
Source:
Type:
Also called CCND1 Gatekeeper of Cell-Cycle Commitment
The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression.
Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.
Cyclin D1 is often found to be overexpressed in various cancers.
Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.
Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.
In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.
Scientific Papers found: Click to Expand⟱
1167- IVM,    The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer
- vitro+vivo, NA, NA
Wnt↓, TCF↓, TumCP↓, Apoptosis↑, β-catenin/ZEB1↓, cycD1/CCND1↓,

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:


Cell Death ⓘ

Apoptosis↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

TCF↓, 1,   Wnt↓, 1,  

Migration ⓘ

TumCP↓, 1,   β-catenin/ZEB1↓, 1,  
Total Targets: 6

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: cycD1/CCND1, cyclin D1 pathway
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#:73  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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