Endovascular Chemotherapy: Selective Targeting for Brain Cancer.

Abstract

Establishing an effective and robust management option for brain cancers has proven to bean elusive challenge for the fields of neurosurgery and neuro-oncology. Despite decades of research efforts to improve treatment outcomes and increase patient survivability, brain cancer remains among the most fatal of all cancer classes. A significant barrier to this endeavor is the blood-brain barrier, a major protective border for brain tissue that primarily precludes the optimal delivery of chemotherapeutic drugs to the patient's brain circulation through tight junction formations and selective transporter proteins. This issue is often compounded by tumor location, particularly in inoperable regions near functional brain parenchyma. These obstacles necessitate the development of selectively targeted delivery of chemotherapeutic agents, such as endovascular super-selective intra-arterial injections. Recent experimental studies demonstrate the effectiveness of focused ultrasound to unseal the blood-brain barrier selectively and reversibly. Together, these new technologies can be leveraged to circumvent the limited permeability of the blood-brain barrier, thus improving drug delivery to tumoral locations and potentially enabling a more effective treatment alternative to surgical resection. This review attempts to place into context the necessity of these newer selective chemotherapeutic modalities by briefly highlighting commonly encountered brain cancers and explaining the prominent challenges that face chemotherapy delivery, as well as describing the current preclinical and clinical progress in the development of facilitatory focused ultrasound with selective endovascular chemotherapy.