Related Experiment Video
Updated: May 24, 2026
07:00
In Vitro 3D Cell-Cultured Arterial Models for Studying Vascular Drug Targeting Under Flow
Published on: March 14, 2021
Vascular disrupting agents: a delicate balance between efficacy and side effects
Antoine Hollebecque1, Christophe Massard, Jean-Charles Soria
1Service d'Innovations Thérapeutiques Précoces, Département de Médecine, Institut Gustave Roussy, Villejuif, France.
Current Opinion in Oncology
|March 14, 2012
Summary
Vascular disrupting agents (VDAs) show promise in cancer therapy by targeting tumor blood vessels. However, their clinical development is hindered by toxicities and a lack of predictive biomarkers, limiting their efficacy in trials.
Area of Science:
- Oncology
- Vascular Biology
- Drug Development
Background:
- Targeting tumor vasculature is a key strategy in cancer therapy.
- Vascular disrupting agents (VDAs) induce tumor necrosis by targeting abnormal tumor blood vessels.
- VDAs represent a unique class of anticancer compounds with potential therapeutic applications.
Purpose of the Study:
- To review the clinical development of VDAs, focusing on their safety and efficacy.
- To summarize the current status of VDAs in cancer treatment.
- To highlight challenges and future directions for VDA clinical trials.
Main Methods:
- Systematic review of clinical trial data for VDAs.
- Analysis of safety profiles, including cardiovascular, neurological, and hematological toxicities.
- Evaluation of efficacy data across various tumor types, including anaplastic thyroid carcinoma (ATC) and nonsmall cell lung carcinoma (NSCLC).
Main Results:
- VDAs have shown clinical activity in diverse tumor types such as ATC, NSCLC, ovarian cancer, and sarcoma.
- Clinical development has been challenged by significant toxicities, particularly cardiovascular and neurological when used as single agents, and hematological toxicity in combination regimens.
- Several negative Phase II/III trials in NSCLC, ATC, and castration-refractory metastatic prostate cancer underscore the high risk of failure.
- Lack of predictive biomarkers to identify responsive patients is a major limitation.
Conclusions:
- VDAs are a distinct class of anticancer agents with demonstrated activity but face significant hurdles in clinical development.
- Toxicity profiles require careful management, especially when combined with chemotherapy.
- The identification and validation of molecular predictors of efficacy are critical for the successful advancement of VDAs.
- While objective responses have been observed, VDAs have not consistently demonstrated a survival advantage in major clinical trials, particularly in combination therapies.
Related Concept Videos
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:29Venous Thrombosis III: Interprofessional Care
Venous thrombosis requires effective prevention and treatment strategies to improve patient outcomes and reduce potential complications.Prevention StrategiesHealthcare providers must prioritize preventing venous thromboembolism (VTE) for all adult patients upon admission. Interventions depend on bleeding and thrombosis risk, medical history, current medications, diagnoses, planned procedures, and patient preferences. Patients on bed rest should change positions every two hours and, if not...
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
Angina pectoris, a primary symptom of ischemic heart disease, requires careful pharmacological interventions. In this context, calcium channel blockers (CCBs) and ranolazine have emerged as crucial pharmacotherapeutic agents, providing deep insights into the complexities of angina management.
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
01:21Cytotoxic Edema: Pathophysiology
Cytotoxic edema is a form of cerebral edema characterized by intracellular swelling of neurons, astrocytes, and other glial cells. It develops when the mechanisms responsible for maintaining ionic gradients across the cell membrane become impaired. Under normal physiological conditions, the sodium–potassium ATPase actively transports sodium ions out of the cell and potassium ions into the cell, preserving osmotic balance and enabling electrical signaling. This pump requires a continuous supply...
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...