A common laboratory test that predicted poor outcome from traditional radiation and chemotherapy treatment for head and neck cancers now has been found to predict a good prognosis with treatment of p53 tumor suppressor gene therapy - making it potentially the first predictive biomarker test for a gene-based drug.
Researchers at Introgen Therapeutics, Inc., in Austin, Texas, found that patients with advanced squamous cell carcinoma of the head and neck cancer (SCCHN) whose pre-treatment tumor samples over-expressed p53 protein were significantly more likely to respond to Advexin therapy than those whose tumor showed little p53 protein. Advexin is a gene based drug, injected directly into tumors, which uses an adenoviral vector to deliver the wild type p53 gene to tumor cells.
Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.
"Not only do we now have a way to predict if the gene therapy is likely to succeed, those patients for which it does work are the hardest patients to treat," said Laura L. Licato, Ph.D., associate director for Clinical Research at Introgen. "Accumulation of p53 has corresponded with a poor response to traditional therapies, as well as lower survival and a shorter time to disease progression."
"Selecting those who have the best chance of responding to p53 tumor suppressor gene therapy also helps perfect clinical trial testing," Licato said.
The researchers specifically found, in a subset of patients from phase II clinical trials, that 73 percent of patients with p53-positive tumors responded to the therapy, compared to a 14 percent response in patients with tumors that were p53-negative. Median survival also increased to 11 months for p53-positive patients, compared to 3 months for those with p53-negative tumors.
Head and neck cancer is the fifth most common cancer worldwide. Each year approximately 40,000 Americans are diagnosed with head and neck cancer, and about 11,000 patients will die.
Many cancers have a dysfunction in the p53 pathway that regulates the cell cycle, helping to protect against cancer formation, but researchers estimate that more than 50 percent of head and neck tumors over-express p53 protein. That suggests a defect in protein regulation or that the p53 gene is mutated, incapable of producing effective protein. Tumors that are p53 negative likely have a working p53 gene and protein pathway, as normal p53 levels in cells are typically low.
Advexin is farthest along in federal Food and Drug Administration (FDA) review of any experimental gene therapy, according to Introgen, and has been granted fast track designation for an application of use in head and neck cancer. Results from two phase II clinical trials involving more than 160 SCCHN patients have found that 18 percent of patients treated with Advexin achieved local regional disease control. Two other phase III trials in the disease are underway. According to Introgen's published research, Advexin has also achieved 100 percent response when combined with chemotherapy to treat locally advanced breast cancer, and a 69 percent response when used with radiation to treat non-small cell lung cancer.
Warren Froelich | EurekAlert!
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences