APATONE: applicable to BC?

[Rich66]

APATONE®:

Apatone ® is a clinical phase investigational new drug based on the Norton-Simon hypothesis. This view suggests that tumors given less time to re-grow between chemotherapy treatments are more likely to be destroyed. Apatone enhances efficacy by selectively lowering reduced glutathione and pyridine nucleotides.

The drug has successfully completed phase I/IIa clinical study for safety and as an oral monotherapy for late-stage prostate cancer. In a report to the FDA, investigators Dr. A. Diokno, Chief Medical Officer for William Beaumont Hospital (Michigan) and Dr. J. Summers, Director for Urologic research at Summa Hospital (Ohio), reported: "There is evidence of therapeutic benefit based on PSA kinetics. The more advanced the disease, the more pronounced the effect seemed to be. Additional studies appear warranted for the use of Apatone as a co-adjuvant, or for salvage chemotherapy in the treatment of late stage prostate cancer."

Apatone is currently under consideration for clinical study with chemotherapy in chemorefractory patients with no clinical options that are known to prolong life. Potential applications include augmentation of chemotherapy to allow lower, less toxic doses of common chemotherapeutic agents such as gemcitabine, doxorubicin, 5FU, cyclophosphamide and others.


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ScienceDaily (Oct. 9, 2007) — In a significant advancement in the ongoing battle against cancer, a group of researchers from Summa Health System, IC-MedTech and other institutions have completed the first ever FDA-approved human clinical trial of Apatone®. Demonstrating promising results, Apatone exploits a new strategy to selectively lower the level of compounds within tumor cells that assist in energy production and protect against chemotherapy. This non-toxic approach weakens and kills cancers in a novel way.

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Apatone was discovered by Dr. Henryk Taper from the Catholic University of Leuven in Brussels, Belgium and was developed by Dr. James Jamison and Dr. Jack Summers, both of Summa Health System, and Dr. Jacques Gilloteaux, now with the American University of the Caribbean in St. Maarten. Their groundbreaking discovery found that moderate doses of Apatone eliminate many types of cancer cells, including prostate, bladder, renal and ovarian.
"This strategy targets cancer cells by their inflammatory response," explains Dr. Jamison. "It's a different approach than most other anti-tumor drugs, which target dividing cells or the development of blood vessels within the tumor. Since normal cells use sugars or fats for energy and cancer cells rely on glucose, the real key here is that Apatone resembles glucose. As Apatone preferentially accumulates in cancer cells, it also supplies quinone that weakens and can destroy the cancer cell from within.
"The bottom line is: Apatone selectively targets and kills tumor cells using non-toxic biochemistry that protects surrounding healthy tissue."
Licensed in 2004 to IC-MedTech, Inc., a California-based biotechnology company, the first clinical trial began in 2005 to evaluate the drug in prostate cancer patients. The clinical studies, which were conducted at Summa Health System in Akron, Ohio and with Dr. Ananias Diokno at William Beaumont Hospital in Royal Oak, Mich., examined the safety and effectiveness in 17 end-stage prostate cancer patients for 12 weeks. These patients took Apatone orally each day. The trials were supported by the Beaumont Foundation, Summa Health System and IC-MedTech.
Throughout the trial, investigators monitored prostate-specific antigen (PSA) levels, PSA velocity and PSA doubling times. Although PSA is a protein normally produced by the prostate gland, individuals with prostate cancer have increased levels. PSA velocity is the change of PSA levels over time and PSA doubling time is the time it takes for a patient's PSA level to double.
"The results of the trial are very promising," said Dr. Jamison. "Sixteen of the 17 patients responded positively to the Apatone and 13 showed a decrease in PSA velocity and an increase in PSA doubling time. At the end of the treatment period, 15 patients opted to continue treatment."
Showing delays in the biochemical progression in end-stage prostate cancer patients, the trial successfully demonstrated the safety and efficacy of orally administered Apatone. Research is continuing and insights into how this drug works have lead to collaborations and discoveries in the field of liquid crystal compounds. Apatone is a Liquid Crystal PharmaceuticalTM and has resulted in research sponsored at Summa and with Dr. Chun-che Tsai at Kent State University. This work shows great promise for cancer and other diseases.
"Ultimately, Apatone is intended to be administered intravenously prior to chemotherapy so it can break down the substances in a tumor that protect it from the chemotherapy and allow a greater cell kill," continued Dr. Jamison. "Between cycles and following completion of chemotherapy, Apatone will be taken orally to help prevent or slow tumor regrowth."
Although the researchers are still working to receive FDA approval for chemotherapy in conjunction with Apatone, the FDA granted orphan drug status to IC-MedTech this year for the use of Apatone as treatment for metastatic, or locally advanced, stage III and IV bladder cancer. An orphan drug designation grants special status to a product to treat a rare disease or condition.
Additional clinical trials are planned for intravenous administration of Apatone in patients who have failed chemotherapy.

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Apatone combined with Tolecine

A partnership between Kent State University, Summa Health System and IC-MedTech Inc. has yielded an innovative liquid crystal technology that offers the promise of new drugs which may more effectively manage cancer and other diseases.

The American Cancer Society estimates that nearly 1.5 million new cases of cancer will be diagnosed this year. This crisis has caused the National Cancer Institute to establish a goal of eliminating suffering and death due to cancer by the year 2015.
Kent State University, Summa Health System and IC-MedTech Inc. have taken steps toward that goal. Their collaborative efforts have yielded an innovative liquid crystal technology that offers the promise of new drugs which may more effectively manage cancer and other diseases.
Dr. Chun-che Tsai, Kent State professor of chemistry; Dr. Jim Jamison, manager of Urology, Obstetrics and Gynecology Core Basic Research Laboratory for Summa Health System; and Mr. Tom Miller, president of IC-MedTech Inc., a California-based biotechnology company, have developed a new paradigm in drug discovery based on the pharmacologic properties of liquid crystals called Liquid Crystal Pharmaceuticals™ or LCPs.
Recently, the team gathered at Kent State University’s Office of Technology Transfer to file applications for two new patents: one for a new LCP-based anti-tumor drug called Tolecine™ and another for a formulation that combines Tolecine™ and another LCP, Apatone®.
“The path-breaking discoveries of Dr. Tsai and his colleagues offer compelling proof of the value of university research and the enormous good that can come from collaborations between universities and the private sector,” says Kent State President Lester A. Lefton. “As Kent State researchers tackle cancer and a host of other real-world ills and issues, they are bringing their leading-edge knowledge and creativity to our students and playing a significant role in economic development.”
Though best known for their use in laptops, televisions and cell phones, liquid crystals also include families of organic substances that are essential for all life called lyotropic liquid crystals. Examples of lyotropic liquid crystals include DNA, proteins and cholesterol. LCPs are a unique class of lyotropic liquid crystals that represent novel drug candidates for the treatment of a wide range of diseases.
“Mother nature is the ultimate chemist,” says Tsai. “Although we use creative and sophisticated computer modeling techniques to screen for our candidate compounds, I’m always amazed at how nature puts it all together.”
The most recent research involving LCPs has yielded a new investigational anti-tumor drug called Tolecine™, a compound that also has antiviral and antibacterial applications. Created by Tsai, it has been shown to be even more effective than the current standard of care for herpes.
The team’s second patent application involves a formulation that combines Tolecine™ and another LCP, Apatone®, which attacks cancer cells via multiple pathways to offer improved efficacy. Apatone® has been successfully tested in more than 30 human tumor cell lines at Summa and in a Phase I/IIa clinical trial, which demonstrated a delaying effect in the progression of end-stage cancer patients. In addition, the FDA granted Apatone® orphan-drug status for the treatment of metastatic, or locally advanced, inoperable bladder cancer in August 2007.
Unlike other chemotherapy drugs, TolecineTM and Apatone® have low toxicity and do not target dividing cells. Instead, they are activated by inflammation that occurs in and around tumor cells, sparing healthy cells. “We want to kill cancer cells specifically without killing surrounding tissues,” says Jamison.
Innovative, low-toxicity drugs such as Tolecine™ and Apatone® provide new hope in the battle against cancer and other diseases in the next few years. “Research on LCPs provides a solid scientific foundation for generations of new drugs,” says Miller. Adds Tsai: “LCPs are an untapped frontier from which many new, exciting treatments are now emerging.”
Source : Kent State University

[Rich66]

Pursuing a cancer cure


Spurred by liquid crystal pharmaceuticals’ early promise, researchers aim to find more gems in Kent State’s vast inventory

Chun-che Tsai, a Kent State professor of chemistry, loads samples into an analyzer at his Summa Health System laboratory in Akron. Dr. Tsai and other area researchers are studying the pharmacological uses of liquid crystals. Photo credit: JEFF GLIDDEN/KENT STATE UNIVERSITY + PHOTO ZOOM

By CHUCK SODER

4:30 am, January 26, 2009


Chun-che Tsai hopes that one day, LCPs will be as common as LCDs.

The Kent State University chemistry professor is one of a few Northeast Ohio researchers trying to tap Kent State’s vast knowledge of liquid crystals — the molecules behind the screens of computers, televisions and cell phones worldwide — to fuel the development of liquid crystal pharmaceuticals, or LCPs.

Local researchers have patented multiple new cancer drugs made from liquid crystals, with two drugs in particular showing encouraging results in early tests. Because liquid crystals already control several key functions within human cells, researchers believe drugs made from similar molecules could have a big impact on patients’ lives, as well as Northeast Ohio’s economy. “That’s why we are so excited,” Dr. Tsai said.

Of the two cancer drugs in the works, Apatone, a combination of vitamins C and K3, is the furthest along. An oral version of the drug, designed to weaken tumor cells prior to chemotherapy, already has been tested in humans during clinical trials within Summa Health System in Akron and at William Beaumont Hospital in Royal Oak, Mich.

Summa research scientist Jim Jamison, one of several researchers listed on the Apatone patent, noted that more testing is needed because the researchers eventually want to administer the drug by IV and simultaneously with chemotherapy.

The second drug, Tolecine, has been applied to animals topically and will be administered to animals via IV in a few weeks, Dr. Jamison said.

Unlike Apatone, which first was tested by researchers in Belgium who later worked with scientists in Northeast Ohio, Tolecine was culled from Kent State’s database of 100,000 or so liquid crystal molecules.

Dr. Tsai, who patented the drug, found Tolecine by combing through the database looking for molecules that would mimic resveratrol, a molecule in peanuts and grapes that some researchers say helps prevent and fight cancer. He is exploring other possible uses for the drug, too.

The group of researchers — which also includes individuals from the University of Akron and the Northeast Ohio Universities Colleges of Medicine and Pharmacy in Rootstown — aims to find more Tolecines in Kent State’s database.

“You can see the potential,” Dr. Tsai said. “It’s a frontier.”


They have a dream ...
There are other drugs on the market made from liquid crystals, such as the cancer drug Taxol, Dr. Jamison said. However, the researchers believe liquid crystal drugs have more untapped potential, given their ability to interact with liquid crystal molecules in cells. Cholesterols, proteins and a membrane that surrounds human cells are all liquid crystals, Dr. Jamison said.

Though he noted that the local drug development effort likely would eventually require assistance from major drug companies, Dr. Jamison said he wants the discoveries of the group to be commercialized here in the region.

“Our dream is to keep that technology in Ohio,” he said.

The rights to commercialize the first two drugs have been licensed to IC-MedTech Inc. of San Diego, but that doesn’t mean the technology will be commercialized there.

IC-MedTech CEO Tom Miller is a Northeast Ohio native, and he regularly works with Northeast Ohio researchers. He is raising money on the West Coast to further the development of the drugs.