ABBOTT PARK, Ill., April 13 /PRNewswire-FirstCall/ -- For decades, scientists have looked for new therapies that target cancer. Researchers now know that cancer cells have several unique characteristics -- they require new blood vessels to deliver oxygen and nutrients (angiogenesis), they grow uncontrollably (proliferation), they travel throughout the body (metastasis), and they escape programmed cell death, a natural process by which the body rids itself of damaged or unwanted cells (apoptosis). Robust preclinical data shows that several compounds in Abbott's oncology pipeline interfere with these vital processes. Data on two of these compounds will be presented at the American Association for Cancer Research (AACR) Annual Meeting being held April 14-18 in Los Angeles.
During the meeting, scientists from independent academic institutions and Abbott will present data on Abbott's Bcl-2 family protein inhibitor (ABT-263). This compound, currently in early clinical development, corrects defects in cancer cells that allow them to escape programmed cell death. They will also present data on an investigational PARP inhibitor (ABT-888) that enhances the effectiveness of common cancer therapies that damage DNA in cancer cells.
Presentation highlights include: ABT-263 -- "ABT-263: An orally bioavailable Bcl-2 family protein inhibitor" [Oral presentation, Sunday, April 15, 1 p.m., Hall A] -- "Pediatric preclinical testing program (PPTP) evaluation of the Bcl-2 inhibitor ABT-263" [Oral presentation, Tuesday, April 17, 3:55 p.m., Room 404 A-B] ABT-888 -- "The poly(ADP-ribose) polymerase (PARP) inhibitor, ABT-888 potentiates the antitumor activity of temozolomide in the B16F10 syngeneic melanoma model: Correlation with pharmacokinetic levels and a reduction in poly(ADP-ribose) polymer by ELISA" [Oral presentation, Tuesday, April 17, 2:40 p.m., Room 404 A-B] -- "ABT-888, a potent PARP inhibitor, enhances the antitumor activities by a variety of chemotherapeutic agents in vivo" [Poster session, Abstract #1457, Sunday, April 15, 1 p.m. - 5 p.m., Poster section 28, Poster 14, Exhibit Hall]
"Cancer accounts for nearly 25 percent of all deaths in the United States, second only to heart disease," said Stephen Fesik, Ph.D., divisional vice president, Cancer Research, Abbott. "Abbott's Oncology Discovery team is dedicated to finding the next generation of small molecule and biologic therapies that will have an impact on this horrible disease."
"There is particular excitement from the scientific community surrounding Abbott's Bcl-2 family protein inhibitors which block the action of a class of proteins that regulate apoptosis," said Fesik. "This ground-breaking program may prove to be extremely valuable in the fight against cancer. In fact, dozens of researchers from around the world are studying Abbott's Bcl-2 family protein inhibitors and will reveal some of their results at this meeting."
Background on Abbott's Oncology Pipeline
Bcl-2 Family Protein Inhibitors (ABT-263)
Researchers have been interested in the Bcl-2 family of proteins since their role in preventing apoptosis -- the natural process by which damaged or unwanted cells die and are cleared from the body -- was proven more than a decade ago. Discovered by Abbott scientists, ABT-263 restores programmed cell death, a natural mechanism for the elimination of cancerous cells, by inhibiting the function of Bcl-2 proteins.
Bcl-2 proteins play a central role in regulating apoptosis, as well as tumor formation, tumor growth and resistance to treatment. Pioneering work in structural biology at Abbott established how the Bcl-2 family of proteins interact with one another, leading researchers to develop a novel compound that causes cancer cells to self-destruct.
ABT-263 recently entered Phase I clinical trials for lymphomas and solid tumors, including small cell lung cancer. Preclinical data has shown that Abbott's Bcl-2 family protein inhibitors bind to Bcl-2 proteins, restoring cell death to cancerous cells. Additionally, the compounds were found to enhance the effects of chemotherapy and radiation used to treat other types of cancer, such as non-small cell lung cancer.
PARP Inhibitors (ABT-888)
DNA damaging agents remain some of the most successful treatments for cancer. The enzyme Poly(ADP-ribose)polymerase (abbreviated PARP) can help repair DNA damage caused by these agents used to treat cancer and render them ineffective. As PARP activity is often increased in cancer cells, it provides these cells with a survival mechanism.
ABT-888 is an oral PARP-inhibitor developed by Abbott researchers to prevent DNA repair in cancer cells and increase the effectiveness of common cancer therapies such as radiation and alkylating agents.
ABT-888 has entered a Phase 0 trial for patients with refractory solid tumors and lymphoid malignancies, and will enter Phase I trials for melanoma this year. Preclinical data indicates ABT-888 has improved the effectiveness of radiation and many types of chemotherapy in animal models of cancer.
Kinase Inhibitors (ABT-869)
Many oncology researchers are currently developing agents that target kinases, a class of enzymes that are often overly activated in cancer cells. Inhibition of the appropriate kinases can suppress tumor growth by cutting off its blood supply.
Discovered by Abbott scientists, ABT-869 is a multitargeted kinase inhibitor that is in Phase I clinical trials for solid tumors and selected hematologic malignancies such as leukemia. Phase II trials for several tumor types will also begin this year. Data presented at previous AACR meetings highlighted the antitumor effects of ABT-869 across a broad range of tumor models.
Other Compounds
Abbott scientists remain dedicated to exploring a variety of cutting-edge treatments in the fight against cancer. In addition to Bcl-2 family protein inhibitors, PARP inhibitors and kinase inhibitors, other compounds moving through the development pipeline include ABT-751, an oral, once-daily antimitotic (a class of drugs that inhibit cell division) in ongoing studies for non-small cell lung cancer, and ABT-828, a biologic compound that blocks angiogenesis of cancer cells.
About Abbott Oncology
Abbott Oncology is committed to the discovery and development of innovative cancer treatments that enable patients to live longer and healthier lives. Abbott's oncology research is focused on developing more targeted, less toxic therapies than are currently available to improve the quality of life for some patients living with cancer.
About Abbott
Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs 65,000 people and markets its products in more than 130 countries.
Abbott's news releases and other information are available on the company's Web site at http://www.abbott.com.
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