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Targeted Cancer Therapies

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Drug Repurposing by Tumor Tissue Editing.

Florian Lüke^1,2, Dennis Christoph Harrer¹, Pan Pantziarka³

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

Frontiers in Oncology

|July 11, 2022

Summary

This summary is machine-generated.

This study explores a novel cancer therapy approach using drug combinations to alter tumor tissue, making it more susceptible to existing treatments. This "tissue editing" strategy offers new therapeutic possibilities beyond direct tumor cell elimination.

Keywords:

PPAR γ anakoinosis biomodulation mTOR metronomic chemotherapy molecular diagnostics pioglitazone umbrella trial

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Area of Science:

Oncology
Pharmacology
Cancer Research

Background:

Conventional cancer therapy often focuses on direct tumor cell apoptosis.
An alternative strategy involves modifying tumor tissue biology through drug combinations.
This includes inducing differentiation, transdifferentiation, or altering cell death mechanisms.

Purpose of the Study:

To investigate the therapeutic potential of "tissue editing" using regulatorily active drug combinations.
To explore how modifying tumor tissue can create new targets for approved drugs.
To establish a framework for selecting and administering drugs for this novel approach.

Main Methods:

Utilizing repurposed, regulatorily active drug combinations to target different tumor cell compartments.
Employing a two-step drug repurposing procedure: establishing new tissue states and then targeting them.
Developing novel preclinical functional assays to test drug combinations in tumor tissue.

Main Results:

Combinatory drug administration can induce biological changes in tumor tissues, creating new therapeutic 'hallmarks'.
Modified tumor tissues present novel target sites, enhancing the efficacy of previously less active drugs.
Regulatorily active doses can be lower than maximum tolerable doses, integrating both inhibitory and stimulatory drug activities.

Conclusions:

Tissue editing represents a paradigm shift in cancer therapy, moving beyond direct cell killing.
This approach facilitates systematic drug repurposing by creating new therapeutic vulnerabilities.
Novel drug selection and administration strategies, including metronomic scheduling, are crucial for successful tissue editing and targeting.