Navigation Links
Potential new drug effective in breast cancer and melanoma resistant to targeted therapies

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
American Association for Cancer Research

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:
(Date:11/25/2015)... ... November 25, 2015 , ... TyloHelo Inc , ... accessories. , Sauna accessories help improve the bather experience in the sauna, and ... styles for the purist looking for simplicity in design to accessories that encourage ...
(Date:11/25/2015)... ... 2015 , ... According to an article published November 10th by ... heralded as a breakthrough for performing hernia repairs. The article explains that the biggest ... that it can greatly reduce the pain that a patient might otherwise experience after ...
(Date:11/25/2015)... ... November 25, 2015 , ... The McHenry County law firm ... appellate decision obtained by Attorneys Francisco J. Botto and Alex C. Wimmer. Attorneys Botto ... Compensation Comm’n, 2015 IL App (2d) 130884WC. , According to court documents, Adcock testified ...
(Date:11/25/2015)... ... November 25, 2015 , ... Brillianteen, McGaw ... and learning in its 65th Anniversary Brillianteen Revue, scheduled for March 4-6, 2016. ... For 65 years, Brillianteen has been a treasured tradition for numerous families in ...
(Date:11/25/2015)... ... 25, 2015 , ... In honor of Pulmonary Hypertension Awareness ... groups responsible for advancing care for pulmonary hypertension (PH) patients and helping to ... will receive special recognition throughout 2016 as part of PHA’s 25th anniversary celebrations. ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... DUBLIN , Nov. 25, 2015 /PRNewswire/ ... announced the addition of the "Global ... to their offering. --> ... "Global Brain Monitoring Devices Market 2015-2019" ... Research and Markets ( ) ...
(Date:11/25/2015)...  Linden Care, LLC, a retail specialty pharmacy focused ... suffering from chronic pain, said today that it is ... (TRO) enjoining Express Scripts from unilaterally terminating the Pharmacy ... --> --> The company said that ... --> --> In ...
(Date:11/25/2015)... Nov. 25, 2015  Henry Schein, Inc., the world,s ... office-based dental, medical and animal health practitioners, will unveil ... Henry Schein ConnectDental® Pavilion , which brings together ... open solutions designed to help any practice or laboratory ... for a schedule of experts appearing at the ...
Breaking Medicine Technology: