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Gene Therapy
The first definition of Gene Therapy was given in the 1970s. Gene therapy meant replacing a gene that was not functional with its functional version. When talking about cancers, Gene Therapy more widely refers to delivering genetic information capable of either directly killing the cancer cells or stimulating the immune system to fight them. There are different types of Gene Therapy, depending on the vehicle (what carries the drug and takes it to the tumor site) used. Common vehicles are viruses which can carry different genes such as: suicide genes, tumor suppressor genes and immunomodulatory genes.

Suicide Genes
Suicide gene therapy involves delivering an inactive prodrug with the enzyme that is supposed to activate the drug itself. This enzyme is the suicide gene. Suicide genes have the advantage of having a bystander cytotoxic effect which is the capability of spreading the cytotoxicity of the drug from the site of affection to the neighboring cells. An example of suicide gene is HSV-TK.

Tumore Suppressor Genes
Tumor suppressor genes are often deleted or inactivated in tumors. They are critical as they help regulate cell proliferation and apoptosis. The purpose of delivering tumor suppressor genes is to restore tumor suppressor activity. One of the most important regulators fro controlling growth and apoptosis is p53 (which is inactive in 65% of secondary glioblastomas).

Immunomodulatory Genes
Immunomodulatory genes are genes engineered in such a way that they can activate and gather an immune response against the tumor. Therefor, the Immune System of the patient can fight cancer cells. An example of virus capable of carrying those types of genes is IFN-beta (Interferon beta) Though, viruses besides carrying genes that affect the tumor cells, can also be the infecting agent itself. Those types of viruses are called Oncolytic Viruses. They have two major advantages: they tend to be specific towards tumor cells that specifically affect the brain and while attacking cancer cells, they are capable of not lysing normal cells, leaving them undamaged.

Stem Cells
Other vehicles are stem cells (SC) which have an advantage that other vehicles do not have: they can migrate and reach dispersed tumor cells in the brain which is a feature of glioblastoma.

Neural Stem Cells
Neural Stem Cells (NSC) fit well in the environment of the brain as a consequence of their ability to differentiate into neurons or glial cells. Among their advantages are the capability of carrying the virus towards more peripherical areas than compared to using viruses alone, the ability of protecting the virus and they are removed from the patient's body after therapy through their own lysis. Common Neural Stem Cells are interleukins like IL-4, IL-12 and IL-23.

Mesenchymal Stem Cells
Mesenchymal Stem Cells (MSC) are adult and non-hematopoietic stem cells. They can be isolated and then expanded in vitro. They have the property of going towards sites of injury and inflammation. Since tumors act as wounds, they tend to attract those types of cells, leading to a strong response of the Immune System against the cancer cells.

Embryonic Stem Cells
Embryonic Stem Cells (ESC) are cells part of the inner cell mass of the blastocyst during gestation and can proliferate with no limits. They can be converted to cells that are strongly attracted to gliomas. Their disadvantage is that they are difficult to obtain and culture.

Chemotherapeutic combinations
Temozolomide (TMZ), a common chemotherapeutic used in treating cancers is a pro-drug. It must be activated by the metabolism of the body to fight cancer cells. Among novel therapies to fight brain cancer, are the combination of different chemotherapeutics/inhibitors with the purpose of enhancing the efficacy of temozolomide.

RIST Therapy
The RIST Therapy is a combination of chemotherapeutics and inhibitors (their initials give the name to the therapy). Those are: Rapamycin, irinotecan, sunitinib and temozolomide. This kind of therapy is called multi target combination (MTC). This approach is a consequence of the fact that tumor cells use different pathways to escape drugs, therefor targeting multiple of those at the same time might show better efficacy than targeting only one. Rapamycin inhibits mTOR, a protein kinase that regulates cell growth and proliferation. Sunitinib inhibits tyrosine kinase. irinotecan and temozolomide, both chemotherapeutics, induce apoptosis.

Ennio Antonio Chiocca
Ennio Antonio Chiocca (born in Padova, Italy) is an Italian-American neurosurgeon. He is the in-Chief and Chairman of the Department of Neurosurgery at Brigham and Women’s Hospital in Boston.

Career
Chiocca graduated with a MD, PhD from the University of Texas Medical School at Houston in 1988 and completed his residency at Massachusetts General Hospital in Boston in 1995. Chiocca became in 2004 the Chair of the Department of Neurosurgery at Ohio State University. He then left to fill the same position at Brigham and Women’s Hospital in 2012. In 2014 he was added to the Institute of Medicine (IOM), which is one of the greatest honors and that includes those that have achieved illustrious success.

Works
His laboratory focuses on finding new genetic therapies for treating malignant brain tumors. Most of the research involves using modified viruses capable of killing tumor cells while sparing normal ones. Current projects include: Engineering Herpes virus which can kill brain tumor cells Finding a way for stimulating an immune response against tumors Studying of indirubins (inhibitors) that are capable of reducing tumor growth and spreading in the brain

Titles
In-Chief and Chair of the Department of Neurosurgery at Brigham and Women’s Hospital. Co-Director of the Institute for the Neurosciences. Harvey W. Cushing Professor of Neurosurgery at Harvard Medical School. Surgical Director at Dana-Faber Cancer Institute. Member of Institute of Medicine.