Improving drug delivery to solid tumors: priming the tumor microenvironment

Area of Science:

• Oncology
• Nanomedicine
• Cancer Biology

Background:

• Tumor growth alters the microenvironment, driving progression, invasion, metastasis, and drug resistance.
• Enhanced permeability and retention (EPR) effect and active targeting strategies face limitations due to tumor barriers.
• Abnormal tumor vasculature, extracellular matrix, and interstitial hypertension impede drug distribution.

Purpose of the Study:

• To investigate the tumor microenvironment as a target for improving cancer drug delivery.
• To explore strategies for modulating the tumor microenvironment to overcome drug resistance.
• To evaluate the potential of
• solid tumor priming
• in enhancing therapeutic efficacy.

Main Methods:

• Review of recent evidence on tumor microenvironment barriers to drug delivery.
• Analysis of mechanisms hindering nanoparticle and small-molecule drug distribution.
• Examination of
• solid tumor priming
• strategies, including vascular normalization and solid stress alleviation.

Main Results:

• Tumor microenvironment abnormalities present significant barriers to effective drug delivery.
• Imperfect EPR and targeting effects are linked to vascular dysfunction, matrix changes, and high interstitial pressure.
• Solid tumor priming strategies show promise in improving drug delivery and anticancer efficacy.

Conclusions:

• The abnormal tumor microenvironment is a viable target for enhancing drug delivery and overcoming resistance.
• Solid tumor priming offers a novel approach to improve chemotherapy and combination regimens.
• Modulating the tumor microenvironment may lead to reassessment of previously ineffective cancer therapies.