The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses
The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses
The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses
Abstract
Despite scientific advances in understanding the causes and treatment of human malignancy, a persistent challenge facing basic and clinical investigators is how to adequately treat primary and metastatic brain tumors. The blood-brain barrier is a physiologic obstruction to the delivery of systemic chemotherapy to the brain parenchyma and central nervous system (CNS). A number of physiologic properties make the endothelium in the CNS distinct from the vasculature found in the periphery. Recent evidence has shown that a critical aspect of this barrier is composed of xenobiotic transporters which extrude substrates from the brain into the cerebrospinal fluid and systemic circulation. These transporters also extrude drugs and toxins if they gain entry into the cytoplasm of brain endothelial cells before they enter the brain. This review highlights the properties of the blood-brain barrier, including the location, function, and relative importance of the drug transporters that maintain this barrier. Primary and metastatic brain malignancy can compromise this barrier, allowing some access of chemotherapy treatment to reach the tumor. The responsiveness of brain tumors to systemic treatment found in past clinical research is discussed, as are possible explanations as to why CNS tumors are nonetheless able to evade therapy. Finally, strategies to overcome this barrier and better deliver chemotherapy into CNS tumors are presented.
blood-brain barrier chemotherapy drug transporters ABC transporters
http://m.clincancerres.aacrjournals.org ... d=17363519
Debbie
Primary and Metastatic Brain Tumors
Primary and Metastatic Brain Tumors
Primary and Metastatic Brain Tumors
May 01, 2014 | Cancer Management
By Nicole A. Shonka, MD, Jay S. Loeffler, MD, Daniel P. Cahill, MD, PhD, and John de Groot, MD
Overview
Intracranial neoplasms can arise from any of the structures or cell types present in the cranial vault, including the brain, meninges, pituitary gland, skull, and even residual embryonic tissue. The overall annual incidence of primary brain tumors in the United States is approximately 20 cases per 100,000 person-years. In 2014, it is estimated that cancer of the brain and central nervous system (CNS) will be diagnosed in 22,810 men and women.. The 5-year relative survival rate following this diagnosis is 33.8%.
The most common primary brain tumors are meningiomas, representing 34.7% of all primary intracranial tumors. Gliomas are the second most common primary brain tumor, at 30%, and account for 80% of malignant primary intracranial tumors. In children, primary brain tumors are the most common of the solid tumors and the second most frequent cause of cancer death after leukemia.
Brain metastases (secondary brain tumors) occur in approximately 15% of cancer patients as a result of hematogenous dissemination of systemic cancer, and the incidence may be rising because of better control of systemic disease. Lung and breast cancers are the most common solid tumors that metastasize to the CNS. Proportionate to their incidence, melanoma and testicular and renal carcinomas have the greatest propensity to metastasize to the brain, but their relative rarity explains the low incidence of these neoplasms in large series of patients with brain metastases. Patients with brain metastases from nonpulmonary primaries have a 70% incidence of lung metastases. Although many physicians presume that all brain metastases are multiple, in fact, half are single and many are potentially amenable to focal therapies.
http://www.cancernetwork.com/cancer-man ... ain-tumors
Primary and Metastatic Brain Tumors
May 01, 2014 | Cancer Management
By Nicole A. Shonka, MD, Jay S. Loeffler, MD, Daniel P. Cahill, MD, PhD, and John de Groot, MD
Overview
Intracranial neoplasms can arise from any of the structures or cell types present in the cranial vault, including the brain, meninges, pituitary gland, skull, and even residual embryonic tissue. The overall annual incidence of primary brain tumors in the United States is approximately 20 cases per 100,000 person-years. In 2014, it is estimated that cancer of the brain and central nervous system (CNS) will be diagnosed in 22,810 men and women.. The 5-year relative survival rate following this diagnosis is 33.8%.
The most common primary brain tumors are meningiomas, representing 34.7% of all primary intracranial tumors. Gliomas are the second most common primary brain tumor, at 30%, and account for 80% of malignant primary intracranial tumors. In children, primary brain tumors are the most common of the solid tumors and the second most frequent cause of cancer death after leukemia.
Brain metastases (secondary brain tumors) occur in approximately 15% of cancer patients as a result of hematogenous dissemination of systemic cancer, and the incidence may be rising because of better control of systemic disease. Lung and breast cancers are the most common solid tumors that metastasize to the CNS. Proportionate to their incidence, melanoma and testicular and renal carcinomas have the greatest propensity to metastasize to the brain, but their relative rarity explains the low incidence of these neoplasms in large series of patients with brain metastases. Patients with brain metastases from nonpulmonary primaries have a 70% incidence of lung metastases. Although many physicians presume that all brain metastases are multiple, in fact, half are single and many are potentially amenable to focal therapies.
http://www.cancernetwork.com/cancer-man ... ain-tumors
Debbie