Navigation Links
Researchers find new target for stopping tumors developing their own blood supply
Date:11/18/2010

Researchers have found that a newly developed drug, which is aimed at a particular receptor involved in the development of blood vessels that sustain tumour growth, is active in patients with advanced cancers and, in some cases, has halted the progress of the disease. The drug, ACE-041, targets a different molecular pathway to other anti-angiogenesis drugs and may provide a new option to treat cancer.

Results from a phase I clinical study of ACE-041 were presented at the 22nd EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Berlin today (Friday). The drug targets a receptor known as activin receptor-like kinase-1 (ALK-1), which regulates the formation of new networks of blood vessels needed for tumour growth a process known as angiogenesis. While existing anti-angiogenic drugs such as bevacizumab, sunitinib and sorafenib target other angiogenesis receptors such as VEGF, ACE-041 is one of the first to target the ALK-1 pathway.

Professor Sunil Sharma, the Jon and Karen Huntsman Presidential Professor of Cancer Research at the Huntsman Cancer Institute, University of Utah, Salt Lake City (USA), told the meeting that the connection of ALK-1 with angiogenesis was made with the discovery that mutations in the ALK-1 gene caused a condition known as hereditary haemorrhagic telangiectasia 2 (HHT2), which is characterised by impaired formation of capillary beds and causes red markings on the skin.

Acceleron Pharma, a biotechnology company in Cambridge, Massachusetts (USA), designed ACE-041 to inhibit ALK-1 signalling and asked Prof Sharma to be one of the investigators to conduct the first-in-man phase I clinical trial of the drug to see if it would inhibit tumour angiogenesis.

"Since ALK-1 is only transiently expressed on proliferating endothelial cells (the cells that line the inner surface of blood vessels), in contrast to the VEGF receptors which are constitutively expressed on endothelial and other cells, it may be a more selective target for the inhibition of angiogenesis," said Prof Sharma. "ALK-1 expression on tumour vasculature has been noted on tumour biopsy samples from a wide range of tumour types."

The phase I study enrolled patients with a range of advanced solid tumours that had spread to other parts of the body or that were inoperable, such as multiple myeloma, non-small cell lung cancer (NSCLC), head and neck cancers and carcinoid tumours (carcinoma-like neuroendocrine tumours that typically originate in the small intestine or appendix). Most patients had been treated unsuccessfully with a range of other treatments, including anti-VEGF drugs, before joining the trial. They were treated as out-patients and ACE-041 was given via subcutaneous injection.

"As of early September, 25 patients have been enrolled in the study, and we have escalated from the starting ACE-041 dose level of 0.1 mg/kg up to 4.8 mg/kg. One patient with head and neck cancer had a partial response, three patients have had stable disease and several other patients have had strongly positive responses as shown by FDG-PET scans. So far, ACE-041 has been well tolerated, with the most common adverse events being peripheral oedema, fatigue, anaemia, headache and nausea," said Prof Sharma.

"It has been very encouraging to see so many signals of efficacy in this trial, in particular because of the study population. These are end-stage cancer patients, who have already been treated with and become refractory to multiple lines of standard therapy. It has also been encouraging to see signals of ACE-041 activity in a wide range of tumour types, since this aligns with our hypothesis that ACE-041 may have anti-tumour activity in any tumour that has angiogenic activity, regardless of tumour histology. It is also important to note that while we have demonstrated significant activity with ACE-041 monotherapy in this study, we might expect to see even more efficacy in future studies with ACE-041 used in combination with other therapies."

Prof Sharma and his colleagues are planning further investigations of the safety and tolerability of the drug in an additional group of patients and hope to start phase II studies of ACE-041 in 2011.

"The anti-VEGF angiogenesis inhibitors, including bevacizumab, sunitinib and sorafenib, have been an important addition to the armamentarium of anti-cancer therapies," said Prof Sharma. "However, their efficacy is somewhat limited since tumours eventually develop the ability to stimulate angiogenesis with non-VEGF angiogenic factors. They also have serious side-effects that arise from effects on blood vessels in normal tissues. Since ACE-041 inhibits angiogenesis in a completely different way, it may have synergistic efficacy with VEGF-inhibitors, and be effective in patients who have developed resistance to VEGF-inhibitors."


'/>"/>

Contact: Emma Mason
wordmason@mac.om
ECCO-the European CanCer Organisation
Source:Eurekalert

Related medicine news :

1. Researchers identify PTSD measures for use in traumatic brain injury research
2. New insight into the cause of common dementia found by researchers at Mayo Clinic
3. Researchers fight Americas other drug problem
4. Researchers map the way to personalised treatment for ovarian cancer
5. Four NYU researchers receive New York Academy of Sciences 2010 Young Scientists awards
6. AAPS presents awards to exemplary researchers
7. Yerkes researchers present at 40th Annual Society for Neuroscience Conference
8. Researchers see ethical dilemmas of providing care in drug detention centers
9. Circuit regulating anti-diabetic actions of serotonin uncovered by UT Southwestern researchers
10. U of M researchers find learning in the visual brain
11. Researchers discover important link between adrenal gland hormone and brain in hypertension
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2017)... ... May 24, 2017 , ... Myers Jackson is well known for ... to sell luxury homes anywhere on the planet. The luxury home market is alive ... to Houston city-scapes. A quick search of “11 Spyglass Hill Auction will enlighten you ...
(Date:5/24/2017)... ... May 24, 2017 , ... ... to its solutions portfolio. ExtraHop delivers an analytics-first approach, layered with machine learning, ... system, from the datacenter to the cloud to the edge. Through the new ...
(Date:5/24/2017)... ... May 24, 2017 , ... The CFOs included on this ... systems in the nation and help their organizations navigate the challenges in healthcare ... instrumental in developing successful hospital and health system strategy. , Becker's Hospital Review ...
(Date:5/23/2017)... ... May 23, 2017 , ... MDLand International (MDLand), ... announced today that its iClinic V12.2 solution has achieved approval from National Center ... introduced PCMH 2017 standards which emphasize team-based care with a significant focus on ...
(Date:5/23/2017)... Cambridge, MA (PRWEB) , ... May 23, 2017 ... ... compensation claim in North Carolina have remained steady since 2009, according to a ... pre-2009 era. , The study Monitoring the North Carolina System: CompScope™ Benchmarks, ...
Breaking Medicine News(10 mins):
(Date:5/8/2017)... -- Diplomat Pharmacy, Inc. (NYSE: DPLO)., has completed its acquisition ... care service center company based in Chantilly, ... management programs for leading pharmaceutical manufacturers and health care ... will join Envoy Health Management, LLC , as ... firms, and other service companies. Together, WRB and EnvoyHealth ...
(Date:5/4/2017)... May 4, 2017  A recent study published ... Ultraviolet-C light as a means of disinfection ... to reduce bioburden on anesthesia workstations. In the ... high-touch, complex medical equipment surfaces contaminated with three ... "This study further validates the body of ...
(Date:5/4/2017)... --  BioLife Solutions , Inc. (NASDAQ: BLFS ... clinical grade hypothermic storage and cryopreservation ... that the Company,s first quarter 2017 financial results will ... 2017, and that the Company will host a conference ... afternoon. Management will provide an overview of the Company,s ...
Breaking Medicine Technology: