itraconazole / LC3B Cancer Research Results

itraC, itraconazole: Click to Expand ⟱
Features:
Itraconazole is a medication used in the management and treatment of fungal infections.

Itraconazole (ITZ; brand Sporanox) — oral triazole antifungal (drug). Oncology relevance is mainly repurposing research (not an approved anticancer indication).

Primary mechanisms (conceptual rank):
1) ↓ Ergosterol synthesis via fungal CYP51 inhibition (primary approved antifungal MoA)
2) ↓ Hedgehog signaling (SMO pathway inhibition; anticancer repurposing)
3) ↓ Angiogenesis / endothelial signaling (anti-angiogenic effects reported; AKT/mTOR signaling suppression in endothelium models)
4) ↑ Autophagy / cell-cycle arrest (model-dependent anticancer phenotypes)

Bioavailability / PK relevance: Oral bioavailability ~55%; capsules absorb best with a full meal; reduced by low gastric acidity (PPIs/H2 blockers). Strong CYP3A4 inhibitor with major drug–drug interaction burden; boxed warning/avoid in ventricular dysfunction/CHF except for serious infections.

In-vitro vs oral exposure: Many anticancer in-vitro effects occur at concentrations that may exceed (or sit near the upper range of) achievable systemic exposure; clinical relevance is formulation/PK-limited and indication-specific.

Clinical evidence status: Approved antifungal; oncology evidence is preclinical + small human/phase II repurposing signals (no oncology RCT approval).


Cancer pathways:
-inhibit VEGF
-inhibit Hedghog Signaling Pathway
-P-glycoprotein Inhibition
-mTOR Pathway

Itraconazole — Cancer vs Normal Cell Pathway Map

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Hedgehog (SMO → GLI) ↓ (model-dependent) ↔ R/G Reduced HH-driven proliferation Repurposing core: inhibits SMO/HH signaling in HH-dependent tumors (e.g., BCC contexts); not an approved oncology indication.
2 Angiogenesis (endothelial growth signaling) ↓ vascular support ↓ endothelial proliferation (context-dependent) R/G Anti-angiogenic effect Identified in repurposing screens as anti-angiogenic; often framed via endothelial signaling suppression (AKT/mTOR in some models).
3 AKT / mTOR ↓ (model-dependent) ↓ (endothelium; context-dependent) R/G Reduced anabolic/survival signaling Reported in endothelial and some tumor models; often tied to growth inhibition and vascular effects.
4 Autophagy ↑ (model-dependent) ↔ / ↑ (stress-dependent) R/G Stress adaptation / growth arrest Often described as autophagic growth arrest; can be cytostatic or contribute to death depending on context.
5 Cell cycle ↓ proliferation ↔ G Checkpoint arrest Phenotype reported across models; typically requires sustained exposure.
6 Apoptosis (intrinsic; caspases) ↑ (model-dependent) ↔ / ↑ (high exposure) R/G Programmed cell death Usually secondary to pathway inhibition / metabolic stress; varies by tumor type and exposure.
7 ROS ↔ (not primary) ↔ P/R No dominant redox program ROS is not a canonical primary ITZ mechanism versus HH/angiogenesis; include only with model-specific evidence.
8 NRF2 ↔ ↔ R/G No primary modulation No consistent NRF2-first mechanism at therapeutic exposure in the repurposing literature.
9 Ferroptosis ↔ (insufficiently established) ↔ R/G Not a canonical ITZ axis Not a standard mechanistic claim for ITZ; treat as investigational unless a specific study supports it.
10 HIF-1α ↓ (indirect; context-dependent) ↔ G Hypoxia/angiogenesis coupling reduction Primarily indirect via anti-angiogenic effects; tumor hypoxia biology can be complex.
11 Ca²⁺ signaling ↔ ↔ P/R No primary role Not a recognized primary ITZ axis.
12 Clinical Translation Constraint ↓ (constraint) ↓ (constraint) — DDIs + exposure variability Major constraints: CYP3A4 inhibition (drug–drug interactions), absorption dependence on meal/acidity, CHF/ventricular dysfunction warning, and repurposing effects that may require higher exposure or specific tumor dependence (HH).

TSF legend: P: 0–30 min (direct target engagement); R: 30 min–3 hr (acute signaling shifts); G: >3 hr (gene-regulatory/phenotype outcomes)
LC3B, microtubule-associated protein 1 light chain 3 beta: Click to Expand ⟱
Source:
Type:
LC3B (microtubule-associated protein 1 light chain 3 beta) is a key protein involved in the autophagy pathway and is widely used as a marker to assess autophagic activity in cells. While not a classical immunogenic cell death (ICD) marker, its expression in tumors has been linked with several prognostic implications, often reflecting the balance between autophagy’s tumor-suppressive and tumor-promoting roles.

• LC3B plays a central role in autophagosome formation.
• Its conversion from LC3BI (cytosolic form) to LC3BII (lipidated, membrane-bound form) is a key indicator of autophagy activation.
• LC3B is sometimes evaluated together with other autophagy-related proteins (such as Beclin-1) to generate an overall picture of autophagic activity in the tumor.

– In several cancers (e.g., pancreatic, colorectal, and breast cancers), elevated LC3B levels have been associated with enhanced autophagy, which can promote tumor cell survival under stress conditions (such as hypoxia or chemotherapy).
– Certain studies, particularly in early-stage tumors or specific subtypes, have found that higher LC3B correlates with improved outcomes.
Scientific Papers found: Click to Expand⟱
2177- itraC,    Itraconazole improves survival outcomes in patients with colon cancer by inducing autophagic cell death and inhibiting transketolase expression
- Study, Colon, NA - in-vitro, CRC, COLO205 - in-vitro, CRC, HCT116
OS↑, tumCV↓, Casp3↑, TumCCA↑, HH↓, TumAuto↑, LC3B↑, p62↑, TKT↓,

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:


Redox & Oxidative Stress ⓘ

TKT↓, 1,  

Cell Death ⓘ

Casp3↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Autophagy & Lysosomes ⓘ

LC3B↑, 1,   p62↑, 1,   TumAuto↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

HH↓, 1,  

Functional Outcomes ⓘ

OS↑, 1,  
Total Targets: 9

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: LC3B, microtubule-associated protein 1 light chain 3 beta
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#:312  Target#:1081  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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