What is the proposed mechanism of ivermectin in treating cancer?

1. Direct disruption of cancer-cell signaling: PAK1 and downstream pathways

A recurring theme in preclinical reviews is that ivermectin acts like a molecular multitool, targeting kinases such as p21-activated kinase 1 (PAK1) and thereby perturbing multiple downstream signaling cascades including Akt/mTOR and Wnt/β‑catenin, which reduces proliferation and can induce cell‑cycle arrest in diverse cancer cell lines ^{[1] [5] [4]}.

2. Ion flux, mitochondrial damage and reactive oxygen species as proximate triggers of death

Several studies report that ivermectin increases chloride ion influx or perturbs mitochondrial function, causing membrane hyperpolarization and a burst of reactive oxygen species (ROS); in colorectal and leukemia models ROS and mitochondrial dysfunction are linked to caspase activation and cell death, with ROS scavengers reversing ivermectin’s cytotoxicity in vitro ^{[1] [2] [6]}.

3. Multiple programmed‑death modalities — apoptosis, autophagy and pyroptosis

Preclinical work shows ivermectin can activate classic caspase‑dependent apoptosis (caspase‑3, PARP cleavage), induce autophagy through Akt/mTOR inhibition, and even trigger pyroptotic features (caspase‑1 activity) in some cancer models, suggesting the drug does not have one single death mechanism but rather pushes stressed tumor cells toward several lethal outcomes depending on context ^{[6] [1] [2]}.

4. Immune effects: purinergic signaling, immunogenic cell death and synergy with checkpoints

Independent reports demonstrate ivermectin is a positive allosteric modulator of the ATP/P2X4/P2X7/Pannexin‑1 axis in both immune and tumor cells, promoting extracellular ATP accumulation and immunogenic cancer cell death (ICD) that increases T‑cell tumor infiltration and selectively reduces immunosuppressive myeloid cells and Tregs — mechanistic data used to explain observed synergy with PD‑1 blockade in breast cancer models ^[3].

5. Synergy with other agents and proposed therapeutic niches

Across in vitro and animal studies ivermectin enhanced the activity of chemotherapeutics (e.g., paclitaxel, daunorubicin) and experimental agents (e.g., recombinant methioninase), fueling proposals to repurpose it as an adjunct rather than a stand‑alone cytotoxic; these combination rationales are the basis for early-phase trials listed by the NCI and for calls to study ivermectin as a partner to immunotherapy ^{[7] [4] [8]}.

6. Limits of the evidence and the social context shaping interest

All of the mechanistic claims above derive from preclinical and small-animal work; systematic reviews and cancer‑care organizations stress there is effectively no robust clinical evidence that ivermectin treats cancer in humans and the FDA has not approved it for oncology — clinicians warn that social‑media narratives and anecdote-driven promotion have amplified use despite safety and drug‑interaction concerns ^{[4] [9] [10] [11]}.

7. Hidden agendas, alternative interpretations and research priorities

Enthusiasm is propelled both by legitimate drug‑repurposing logic (cheap, well‑characterized molecule) and by non‑scientific forces—viral anecdotes, influencers, and conflation with COVID‑era ivermectin debates — making rigorous clinical trials essential to separate promising mechanism from illusion; investigators must prioritize dose, safety, mechanisms in human tumors, and objective combination strategies rather than extrapolating from cell lines ^{[5] [9] [12]}.

Bottom line

Mechanistically, ivermectin appears to attack cancer on multiple fronts — kinase signaling (PAK1 → Akt/mTOR/Wnt), ion channels/mitochondria → ROS, induction of diverse programmed‑cell‑death pathways, and by modulating purinergic immune signaling to promote ICD — creating plausible combination strategies with chemotherapy and immune checkpoint inhibitors, but these preclinical mechanisms have not yet produced convincing clinical proof of benefit, and clinicians urge caution amid misinformation ^{[1] [2] [3] [6] [4] [9]}.