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:
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...