Topic: Targeted Therapy
WHAT IS TARGETED THERAPY?
Targeted therapy is a term that refers to a drug or combination of drugs that targets a specific pathway in the growth and development of a tumor. By attacking or blocking these important targets, the therapy helps to fight the tumor itself. The targets themselves are typically various small molecules in the body that are known or suspected to induce cancer formation.
HOW ARE TARGETED THERAPIES NAMED?
The names of the major classes of targeted therapies typically include the word "anti-", or "inhibitor", together with the name of the target itself. This means that the drug blocks, (is "anti"), that particular target. Then within each class of inhibitors, there is/are the actual drug(s).
It is important to realize that a single drug can have several names, including a generic name and a brand name. This can be confusing because often the generic and brand names are used interchangeably in the literature and the media. This means you need to the names to follow the pathways.
What are the different classes of targeted therapy? In other words, what are the different targets?
There are several pathways that have been studied quite intensively and they are:
Kinase: Defintion …Any of various enzymes (proteins) that catalyze the transfer of a phosphate group from a donor, such as ADP or ATP, to an acceptor
1) Map Kinase : Mitogen-activated protein (MAP) kinases (EC 2.7.11.24) are serine/threonine-specific protein kinases that respond to extracellular stimuli (mitogens) and regulate various cellular activities, such as gene expression, mitosis, differentiation, and cell survival/apoptosis
It was studied early on in the Melanoma Research.
2) PI3-Kinase: PI 3-kinases have been linked to an extraordinarily diverse group of cellular functions, including cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. Many of these functions relate to the ability of class I PI 3-kinases to activate protein kinase B (PKB, aka Akt). The class IA PI 3-kinase p110α is mutated in many cancers. Many of these mutations cause the kinase to be more active. The PtdIns(3,4,5)P3 phosphatase PTEN which antagonises PI 3-kinase signalling is absent from many tumours. Hence, PI 3-kinase activity contributes significantly to cellular transformation and the development of cancer. The p110δ and p110γ isoforms regulate different aspects of immune responses. PI 3-kinases are also a key component of the insulin signaling pathway. Hence there is great interest in the role of PI 3-kinase signaling in Diabetes mellitus.).
Another pathway was the c-Kit: Receptor tyrosine kinases, such as c-Kit, are proteins whose function it is to transduce signals from the environment into the cell leading to complex behaviors such as proliferation, migration, survival and differentiation. Many of these behaviors are deregulated in cancer, which is characterized by uncontrolled proliferation, insensitivity towards death stimuli, migration of tumor cells away from the primary tumor site and in some cases also block of cellular differentiation leaving the cell in an immature proliferative state. To be able to target these processes it is vital to have a detailed understanding of the receptor function and the downstream pathways activated.
Well, they developed A c-Kit antigen:
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Example of Targeted Therapy:
THURSDAY, April 17 2008 (HealthDay News) -- The cancer drug Gleevec has forced metastatic melanoma into remission for the first time, report researchers at the Dana-Farber Cancer Institute in Boston.
The case involves a 79-year-old woman with melanoma tumors in several parts of her abdomen. The tumor cells carried an abnormality in a gene called KIT, so the patient was enrolled in a clinical trail of the drug imatinib (Gleevec), which targets the KIT gene.
Four weeks after the woman started therapy, there was dramatic reduction in tumor size and metabolism. Two of the tumor masses had vanished, and several others were much smaller. After four months, the tumors were still in check and, nine months later, the women was still taking the drug and her condition remained stable.
The report was published in the April 20 issue of the Journal of Clinical Oncology .
"This is the first proof of principle that we can find an Achilles' heel in melanoma and by targeting that gene with a drug, cause the [tumor cells] to die. It is especially exciting because there haven't been any effective treatments for melanoma patients with metastatic disease," study author Dr. Stephen Hodi said in a prepared statement.
He said this case may involve just one patient, but should inspire new hope in the fight against melanoma. Because previous research failed to identify any genetic weak point that could be targeted to stop melanoma cell growth, some researchers believed that no such Achilles' heel existed for melanoma cells. The discovery of this one suggests there may be others.
SOURCE: Dana-Farber Cancer Institute, news release, April 17, 2008Melanoma Mutations:
Strategies for attacking melanoma may soon involve a personalized approach based on the genetic characteristics of the patient’s tumor. Recently, scientists have begun to uncover genetic mutations that drive the unchecked growth of melanoma cells. By determining the pathways that caused the mutation, they hope to create drugs that better target the specific problem.
A common genetic mutation in melanoma creates an overactive version of a protein called BRAF, which instigates cell growth and division. Other mutations activate a related protein, called N-RAS, also resulting in unchecked cell division. Drugs designed to block these overactive proteins kill melanoma cells in laboratory tests, but so far they have shown only some promise in patients. So they are starting personalize the therapy base on patient’s tumor genetics.
Near term goal is to control the progression until they can find the silver bullet. So they will use Chemo and Biological to control the Beast for now.
So, hold on to your hats and make sure that if you have a tumor that can be harvested, you should ask your oncologist to get genetic mapping/typing of the tumor. It could send you down the YELLOW BRICK ROAD to the Emerald City.
Another take away is that a cure may be based on personalized therapy. So there might not be just one cure, but many based on genetics.
Source:Oncolink and the Dictionary
Take Care
jimmy B
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