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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Peroxisome proliferator-activated receptorα/γ agonist pioglitazone for rescuing relapsed or refractory neoplasias by

Dennis Christoph Harrer1, Florian Lüke1,2, Tobias Pukrop1,3

  • 1Department of Internal Medicine III, Hematology and Oncology, University Hospital Regensburg, Regensburg, Germany.

Frontiers in Oncology
|January 26, 2024
PubMed

Insights

Pioglitazone, a PPARα/γ agonist, effectively reprograms cancer hallmarks in relapsed or refractory cancers. This tumor tissue editing approach induces cancer cell death and controls resistance, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Relapsed or refractory (r/r) metastatic neoplasias present significant therapeutic challenges.
  • Understanding tumor plasticity and ligand-receptor cross-talk is crucial for developing novel treatments.

Purpose of the Study:

  • To investigate if tumor-specific cancer hallmarks can be targeted using tissue editing approaches with pioglitazone.
  • To evaluate the efficacy of pioglitazone in combination with other modulators in r/r cancers.

Main Methods:

  • Seven clinical trials involving pioglitazone, a dual peroxisome-proliferator activated receptor α/γ (PPARα/γ) agonist.
  • Combinations included transcriptional modulators (all-trans retinoic acid, interferon-α, dexamethasone), metronomic low-dose chemotherapy (MCT), and epigenetic modifiers (azacitidine).
  • Tumor tissue editing strategies were employed to exploit tumor plasticity.

Main Results:

  • Pioglitazone initiated tumor-specific reprogramming of cancer hallmarks, controlling inflammation and inducing differentiation.
  • Complete remission (CR) was observed in r/r non-promyelocytic acute myeloid leukemia (AML) and r/r renal clear cell carcinoma (RCCC).
  • Long-term disease control was achieved in melanoma by managing metastasis and acquired resistance (M-CRAC).

Conclusions:

  • PPARα/γ agonists demonstrate tumor-type agnostic biomodulatory efficacy.
  • Pioglitazone integrated into tissue editing protocols is a promising therapeutic agent for r/r cancers, particularly for managing M-CRAC.
  • Low-dose MCT combined with transcriptional modulators effectively reprograms cancer hallmarks and induces tumor cell death.
Keywords:
all-trans retinoic acidanakoinosisdexamethasoneinterferon-αphenotypic plasticitypioglitazonetranscriptional modulationtumor tissue editing

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