Navigation Links
Potential new drug effective in breast cancer and melanoma resistant to targeted therapies
Date:10/20/2013

BOSTON LEE011, a small-molecule inhibitor of cyclin-dependent kinases (CDK) 4/6 being developed by Novartis Oncology, showed promising results in drug-resistant melanoma and drug-resistant breast cancer when tested in combination with other targeted therapies, and based on these preclinical results, several phase I clinical trials were launched recently, according to results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held October 19-23.

In many cancers, a tumor suppressor protein called retinoblastoma is deactivated because of an increase in the activity of the proteins CDK 4 and 6. This results in unchecked cell proliferation. The activity of CDK4/6 is regulated by cyclin D, whose expression is increased by activation of BRAF and PIK3CA, which are implicated in some melanomas and breast cancers, respectively. Drugs targeting BRAF and PIK3CA have had success, but most treated cancers subsequently develop resistance to these drugs.

"Chemistry optimization has led to the discovery of LEE011, which, to our knowledge, is the most selective CDK4/6 inhibitor to date," said William Sellers, M.D., vice president and global head of oncology at the Novartis Institutes for Biomedical Research in Cambridge, Mass. "Utilizing the latest cancer genomics data and our knowledge of the role of CDK4/6 activity in the growth of tumor cells, we have identified unique indications and combinations of drugs with LEE011, in which LEE011 demonstrates a robust antitumor activity.

"One of the most notable findings is that, when paired with other targeted agents, LEE011 is often able to prevent the emergence of resistance to the partner compound that would otherwise arise when the partner compound is dosed alone."

Based on the results from preclinical experiments, Novartis has initiated multiple phase I trials in adult cancers, and a phase I trial in pediatric cancers is ongoing. "Preliminary data show LEE011 is well tolerated with excellent pharmacokinetic properties," said Sellers. Combination studies of LEE011 and other Novartis pipeline drugs are underway, according to him.

Sellers and colleagues conducted preliminary studies using cancer cells in culture and found that LEE011 inhibited the growth of tumor cells primarily by arresting the cells at a "checkpoint" called G1, which prevents the cell from multiplying. Further in vivo experiments showed that because cyclin D1 is a target of BRAF and PIK3CA, LEE011 was effective as a single agent in mice bearing melanomas with BRAF mutations, and those bearing breast cancers with PIK3CA mutations.

When tested in combination with an investigational BRAF inhibitor, LGX818, in melanoma, LEE011 showed robust antitumor activity in mice sensitive or resistant to LGX818. Similarly, when combined with an investigational PIK3CA inhibitor, BYL719, LEE011 showed significant antitumor activity in mice bearing breast cancers sensitive or resistant to BYL719.

In the phase I clinical trial in adult patients, the investigators are testing LEE011 as a single agent in cancers that are dependent on CDK4/6, including liposarcomas, mantle cell lymphomas, and head and neck cancers. In the ongoing phase I study on pediatric cancers, LEE011 is being tested as a single agent in neuroblastoma and malignant rhabdoid tumors.

"CDK4/6 inhibition offers a new strategy to directly attack the uncontrolled growth that defines cancer. LEE011 is a new and highly selective CDK4/6 inhibitor that Novartis hopes will be of clinical benefit, and we are progressing to patients as quickly as possible," said Sellers.


'/>"/>

Contact: Lauren Riley
lauren.riley@aacr.org
215-446-7155
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. New Research Shows Wild Blueberries Have Potential to Improve Heart Health
2. Macrophage-derived mediators may have potential as biomarkers for urinary stone risk
3. Repurposed antidepressants have potential to treat small-cell lung cancer
4. Quadruple Amputee and Champion Athlete Kyle Maynard to Inspire Special Needs Kids to Meet Greatest Potential
5. Warning of potential side effects of a product can increase its sales
6. McKenzie Management Develops New Tool To Measure Hidden Revenue Potential
7. Potential treatment for a specific kind of pancreatic cancer
8. Approved cancer drug potentially could help treat diabetes, Stanford researchers find
9. Potential Drug AMG Services LDL Reduction, Declared "New Hope" by Home And Recreation Lifestyle Magazine
10. The Holistic Sanctuary Recognizes International Overdose Awareness Day by Citing CIR Report About Potential Fraud at Conventional Drug Rehab Centers
11. Medical Researchers Say They Have Made a Breakthrough That Could Lead to a Potential Cure for AIDS
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/24/2017)... (PRWEB) , ... March 24, 2017 , ... ... to the military at the same time by providing Prehospital Trauma Life Support ... PHTLS is the world’s premier prehospital trauma education developed in cooperation with the ...
(Date:3/24/2017)... (PRWEB) , ... March 24, 2017 , ... ... from third world countries to hospitals in the United States, it’s a threat ... on the current obstacles facing infection prevention and offers strategies for the healthcare ...
(Date:3/24/2017)... ... , ... The Radiology Business Management Association (RBMA) has named the ... their 12th year, are among the most prestigious in radiology marketing because a panel ... retooled to recognize achievements in both large budget (over $5,000) and small budget (under ...
(Date:3/24/2017)... ... ... Texas Physical Therapy Specialists (TexPTS) is pleased to announce the opening ... is the group’s 7th location in San Antonio and 23rd in Texas. Dr. ... from the clinic, which opened March 22, 2017. , The team of ...
(Date:3/24/2017)... ... March 24, 2017 , ... Mlynarek Insurance Agencies, a Detroit ... business owners across eastern Michigan, is connecting with the Oxford/Orion FISH Food Pantry ... , The Oxford/Orion FISH Food Pantry works to ensure homeless, hungry, and underprivileged ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... 2017 Abdominal Aortic Aneurysm Repair Devices Market was valued at $1,844 ... a CAGR of 5.1% from 2016 to 2022. The endovascular stent graft system segment ... during the study period. Continue Reading ... ... ...
(Date:3/24/2017)... Research and Markets has announced the addition of the ... 2022" report to their offering. ... The global wound care market was worth $24,482.9 million in ... during 2016-2022 Among the various wound care products type, the ... market in 2015. Among the various applications, surgical wound segment held the ...
(Date:3/24/2017)... , March 24, 2017 ShangPharma, ... high-quality and cost-effective drug development and discovery ... and biotechnology industry, announced today the intent ... ShangPharma will be consolidating the Contract Research ... under Shanghai ChemPartner. These entities include ChemPartner ...
Breaking Medicine Technology: