Cyclacel’s biomarker technology shows that CYC202 induces cancer cells to commit suicide
Over half of solid tumour patients analysed tested positive for cancer cell death
Cyclacel Limited, the UK-based biopharmaceutical company, reported today that it demonstrated through state-of-the-art biomarker technology that CYC202 (R-roscovitine), its lead CDK inhibitor drug candidate, appears to induce cancer cell suicide or apoptosis in patients receiving the drug. Details of the biomarker data obtained with CYC202 were reported today at an oral presentation at the American Association for Cancer Research (AACR) annual meeting taking place here.
Biomarker technology is used to understand the molecular mechanism of action of novel drugs in humans, provide insights into their pharmacological properties, measure their biological effect (e.g. induce cancer cells to commit suicide) and determine susceptibility or resistance to the treatment. In the long-term biomarker analysis of tumour blood and tissues may allow selective treatment with CYC202 of those patients identified as likely to benefit from the drug based on the specific genetic profile of their tumour.
Biomarker analysis of blood samples from patients with cancer treated with CYC202 demonstrated that 54% (14 of 26 analysed) tested positive for cancer cell death or apoptosis following single agent treatment with the drug. In addition, seven CYC202 Phase I patients with various tumours, including pancreas and lung cancer, experienced long lasting tumour stabilisation. These patients received CYC202 capsules taken by mouth after exhausting other treatment options. CYC202 is presently being tested in two international, multicentre Phase IIa clinical trials for the treatment of breast and lung cancer in combination with standard chemotherapy.
Cyclacel’s Biomarker Team used a novel assay technique to calculate the extent by which cancer cells are committing suicide (or apoptotic index) in different patients on the drug. An advantage of this test is that it measures cellular material released into the circulation by dying or dead cancer cells as a result of apoptosis. In this manner small blood samples can be readily obtained from patients with solid tumours rather than tissue pathology samples obtained through biopsies. Another approach taken by Cyclacel’s Biomarker Team is the study of plasma proteomic profiles allowing the precise comparison of the proteins present in a patient’s plasma before and after treatment with CYC202. Using this approach markers were detected that are only present in plasma following CYC202 treatment.
Phase I trials are not designed to detect efficacy of experimental drugs. Patients enrolled in Phase I studies suffer from many different types of cancer, have typically exhausted other therapeutic alternatives and usually experience low survival. In order to assess their prognosis it is necessary to wait for approximately six months post treatment to determine whether their cancer has continued to grow. The seven patients in the CYC202 Phase I study reported with stable disease included patients with adenocarcinoma, adrenal, lung, ovarian, pancreatic, parotid gland and thymus cancers. All seven showed long Times-To-Progression (“TTP”) of their cancer, ranging between 7 and more than 11 months, and have been on drug for several months, ranging between 6 and more than 15 cycles each involving 3 weeks of treatment.
Dr Athos Gianella-Borradori, Cyclacel’s Medical Director commented, “It is encouraging to see validation of the presumed mechanism by which CYC202 is causing the death of cancer cells through biomarker technology. It is also encouraging to see Phase I patients with poor prognosis experience long periods of stable disease after single therapy with CYC202. One should nevertheless be cautious about not over interpreting early indications of effectiveness from unscheduled efficacy assessments. Now that we have established a baseline for quantifying apoptosis in patients undergoing CYC202 monotherapy, we can use such biomarker techniques to assess the effects of the drug on patients receiving CYC202 in combination with chemotherapy.”
“The results presented at AACR confirm Cyclacel’s technological leadership in the emerging field of biomarkers,” said Spiro Rombotis, CEO. “This is a strategic technology facilitating more efficient investments in drug development programmes. Biomarkers help determine clinical go/no go decisions very early in clinical development and are also proving invaluable in demonstrating early proof of concept in humans. We believe that biomarkers will be a source of competitive advantage in pivotal trials and market positioning by helping identify responder patients based on their genetic profile. We are excited about the work of our talented Biomarker Team and our goal of converting our understanding of biological pathways into patient treatment guidelines. We expect to use our Biomarker technology in additional drug programmes as they progress into clinical trials.”
Cyclacel is a biopharmaceutical company that designs and develops small molecule drugs that act on key cell cycle regulators to stop uncontrolled cell division in cancer and other diseases involving abnormal cell proliferation. The Company’s discovery engines integrate cell cycle biology expertise with a large library of gene-based targets, state-of-the-art RNAi functional genomics, chemogenomics and clinical biomarker technologies to rapidly deliver new drugs. Cyclacel has six research and development programs underway. Most advanced is CYC202, a Cyclin Dependent Kinase (CDK) inhibitor, in Phase II trials for breast and lung cancer. CYC202 has also completed a Phase I trial in healthy volunteers and is being explored for use in glomerulonephritis, a disease of renal cell proliferation. Cyclacel has entered into corporate alliances with AstraZeneca, CV Therapeutics and a top 5 pharmaceutical major all in the oncology field.
Robert Gottlieb | Feinstein Kean Healthcare
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes
The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....
Larsen C Ice Shelf rift finally breaks through
A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...
Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision
Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...