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Cancer therapeutics and drug discovery are vital areas of research and are constantly evolving as we seek to find new methods to cure the disease and develop new treatment options. With its world-class research institutions and a history of genetic discovery, Utah is positioned to become a leader in the cancer therapeutics industry.

Two Utah companies, Mesagen and TheraTarget, are ahead of the curve in Utah when it comes to the advancement of cancer therapeutics.

Getting to the root cause of carcinogenesis

Mesagen is a Salt Lake City-based biological company working on cancer stem cell therapeutics, based in the Utah Science Technology and Research Initiative (USTAR) supported by BioInnovations Gateway. The company has acquired a proteomic database from Myriad Pharmaceuticals which contains 35,000 different protein-protein interactions representing over 5,500 different human proteins. The database is used to discover protein ligands that bind to therapeutic targets for cancer stem cell therapy.

Scott Morham, CEO and CSO of Mesagen, said we get cancer every day, 24 hours a day and seven days a week. Our immune systems mostly wipe the cancer out, but every now and again an early progenitor cell or multipotent cell becomes transformed, thus forming a cancer stem cell that can differentiate into the various types of tissues needed to form a tumor and promote metastasis.

“Think of a tumor more like an organ in the body,” said Morham. “It needs a variety of different cell types to be able to maintain its structure. The tumor needs certain types of cells to create growth factors; it needs endothelial cells to form arteries; it needs mesenchymal cells to promote motility. A wide variety of cells are necessary for malignant tumor formation.”

The only things that can do that are cancer stem cells, according to Morham. Even though current therapies can shrink the tumor itself, and the faster growing differentiated tissue is killed, the cancer stem cells that divide very slowly linger. This means the tumor has shrunk but it will inevitably come back, a common occurrence with almost all therapies. Morham said to actually cure cancer, it’s essential to get rid of the root cause of carcinogenesis.

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“Some of what we’re doing is actually getting at the root cause of carcinogenesis,” said Morham. “Current therapies can shrink the size of tumors. They affect carcinogenic tumor tissue, but cancer stem cells divide slowly and are usually cloaked from the immune system. One of our major modes of getting at them is to reactivate the immune system to see those carcinogenic cancer stem cells and have them be chewed up by macrophages.”

Morham said they have found that most cancers hide themselves from the immune system by expressing a protein called CD47 on their surface, which he likens to an invisibility cloak that sends a “don’t eat me” signal to macrophages, which would normally chew up cancer cells and display the antigens that are required to get a robust immune response.

The goal of Mesagen is not to bring drugs to market, but rather to be an early stage discovery company that brings its discoveries through proof of concept experiments, then collaborating with large pharmaceutical companies through the IND stage of development; after which the pharmaceutical company has the option to license the intellectual property and further develop the therapy.

“Just to get in for a Phase I trial, you’re talking about $10-50 million in cost to generate the protein,” said Morham. “Cancer therapy development is not cheap, that’s why you see all these expensive therapies that are coming up.”

Developing better drug delivery systems

TheraTarget, a developer of drug delivery systems, was incorporated as a spin-off company from the University of Utah. The drug delivery system is based on the research of Jindrich Kopecek and Hamid Ghandehari. Both are professors of pharmaceutics and pharmaceutical chemistry and bioengineering at the U. and co-founders of TheraTarget. Ghandehari is also the director of the Utah Center for Nanomedicine, co-founder and co- director of the Nano Institute of Utah and director of the U.'s nanotechnology training program.

TheraTarget’s targeted drug delivery system uses a polymer backbone administered to a cancer patient who has one of four types of solid tumors: ovarian, lung, breast or pancreatic. When an anti-cancer drug is attached to the polymer backbone, the drug in the bloodstream does not have any toxic effects until it enters the tumor cell. Rapidly growing solid tumors generate many new blood vessels. New blood vessels are very leaky, allowing the polymer backbone with its attached anti-cancer drug to enter the tumor and exert its toxic effect.

“When you give anti-cancer drugs attached to the polymer backbone, they will enter the bloodstream, pass through the leaky blood vessel walls into the cancer cells and release the drug,” said Darwin Cheney, CEO and president of TheraTarget. “It allows the anti- cancer drug to kill the tumor cell, and then the breakdown products can be removed by the kidney.”

Cheney indicated that the University of Utah expressed an interest in using the polymer backbone in some of the hospital’s patients, pending a filing as an investigational new drug application.

“The object of clinical phase 1 studies is to investigate whether the drugs are safe,” said Cheney. “When a drug is quite toxic and is going to be given to a set of patients who are at high risk, we need to be able to identify how much is going to be necessary to give them.”

New USTAR cancer therapeutics team

In addition to these two Salt Lake City based companies, USTAR, in collaboration with the U.'s College of Pharmacy, School of Medicine and the Huntsman Cancer Institute, will be bringing online a new cancer therapeutics team this fall. The objective of the team will be to build on the history of genetic discovery in Utah to advance the development of targeted cancer treatments.

Darrell Davis, professor and chairman of the department of medicinal chemistry, said the new team will help leverage the university's existing strengths in cancer genetics and biology at the Huntsman Cancer Institute in order to bring new therapeutics into the clinic.

“The development of new therapeutics is multidisciplinary, requiring the identification of new cancer targets with initial identification of molecules active against those targets and then the development of those leads into treatments that can be tested in cancer patients,” said Davis. “With the USTAR initiative, we plan to have in place all the components necessary for developing new, more effective treatments."

Elenor is a public relations and marketing assistant for USTAR and supports staff in promoting USTAR's mission. She is currently working towards her bachelor's degree in strategic communication at the University of Utah, and has an expected graduation date of December, 2014. Before coming to USTAR, Elenor worked at the Salt Lake Tribune for three years as a newsroom assistant, and at the Enterprise Business Newspaper for eight years as production manager and copy editor.

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