Navigation Links
'Smart drug' targets new mutation, dramatically shrinks aggressive sarcoma and lung cancer
Date:10/27/2010

BOSTON--A new oral drug caused dramatic shrinkage of a patient's rare, aggressive form of soft-tissue cancer that was driven by an abnormally activated protein, physician-scientists from Dana-Farber Cancer Institute report in the Oct. 28 issue of the New England Journal of Medicine.

A second patient who had a similar tumor that was not fueled by the mutant protein, called ALK (named for the first disease in which it was found, anaplastic lymphoma kinase), failed to respond to the drug, said the researchers, confirming the inhibitor's specificity for the abnormal protein. The findings also highlight the value of "personalized medicine" gene-testing strategies to predict the best drug treatment for an individual's particular, genetically defined cancer.

The patient described in the NEJM Brief Report is a 44-year-old man diagnosed in 2007 with inflammatory myofibroblastic tumor (IMT), a type of sarcoma that typically develops in the chest or abdomen in children and young adults.

In approximately half the cases of IMT, ALK is fused to a different protein in the patients' cancer cells, spurring cancer development. The patient had been treated with standard chemotherapy drugs followed by the targeted compound Gleevec, but the cancer returned in the form of multiple tumors.

James Butrynski, MD and Geoffrey Shapiro, MD, PhD, Dana-Farber oncologists and the first and senior authors of the report, respectively, offered the patient participation in a Phase 1 trial of an experimental drug, crizotinib, which blocks ALK activity, as well as that of another oncogene, MET, that is abnormally activated in a number of cancers.

Crizotinib treatment shrank the tumors by more than 50 percent technically called a "partial response." After several months of crizotinib, in December 2008, some of the tumors became resistant to the drug and started growing again. These tumors, as well as tumors still responsive to crizotinib, were removed surgically. Crizotinib was resumed after the surgery, and the patient remains without evidence of disease as of September 2010, according to the investigators.

The activity of crizotinib goes beyond this rare sarcoma. The current report accompanies a paper in the same journal describing striking activity of crizotinib in a group of patients with non-small cell lung cancers (NSCLC) containing the abnormal ALK protein. Researchers from Massachusetts General Hospital, Dana-Farber/Brigham and Women's Cancer Center, and other hospitals gave crizotinib to 82 patients after standard drugs failed to halt the tumors' growth. As part of the personalized medicine effort ongoing in the Dana-Farber/Brigham and Women's Cancer Center Thoracic Oncology Program, patients with abnormal ALK were identified for the trial, underscoring the importance of tumor profiling to match drug with patient.

Results showed that 47 patients had tumor shrinkage (complete disappearance in one patient) and the cancer stopped growing in 27 patients. The ALK rearrangements are found in a small subset, about 5 percent, of patients with NSCLC, but scientists are searching for other cancers that may also be susceptible to the ALK inhibitor.

Shapiro noted that even highly successful targeted drugs like crizotinib are vulnerable to tumors' developing resistance against them. In fact, the IMT patient's tumors that developed resistance to crizotinib and were removed surgically have been studied by one of the reports co-authors, Pasi Janne, MD, PhD, also of Dana-Farber. In a paper appearing simultaneously in Cancer Research, Janne and his colleagues have identified a secondary mutation in ALK in the patient's tumor that conferred resistance to crizotinib. Furthermore, in work recently published by Janne, Shapiro and their Dana-Farber colleague, Kwok-Kin Wong, MD, PhD, the abnormal ALK proteins, including the protein with the secondary mutation that was resistant to crizotinib, were found to depend on a cellular chaperone, called Hsp90, for their stability. Inhibitors of Hsp90 are currently under clinical evaluation and have been shown to cause destruction of the aberrant ALK proteins.

Crizotinib is one of many targeted agents currently being evaluated by the Early Drug Development Center within the Experimental Therapeutics Program at Dana-Farber, with the aim of translating the best science into effective new therapies for patients with many forms of cancer that can be defined by sophisticated new molecular profiling techniques.


'/>"/>

Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert  

Related medicine news :

1. Cook With Love This Valentines Day With Heart-Smart Recipes
2. ANT+ and Texas Instruments connect proven ultra low power sensors to smartphones
3. Hollywood-Style Liposuction Comes to DC: Chevy Chase Smartlipo Brings Revolutionary Laser-Assisted Liposuction to DC Metro Area
4. Afternoon Nap Might Make You Smarter
5. State of Oregon Department of Human Services Selects Netsmart Technologies for Comprehensive Behavioral Healthcare Integration Project
6. SSI Announces Its Fourth Generation Revenue Cycle Management Technology, ClickON ClaimSmart Suite
7. Brain Cancer Survivor Will Cycle 4,170 Miles Across USA to Outsmart Disease
8. Conference Focuses on Aligning Two Smartest, Most Expensive Operations
9. SDI Reports: Nearly a Third Of Physicians Use Handheld and Smartphone Devices to Access Medical Information - Physicians Most Likely to be Using Apple iPhone
10. Smart Balance to Present at Roth Growth Stock Conference
11. PA Hypnosis Center Uses 'Smart Training' Sports Psychology for Gold Medal Success
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
'Smart drug' targets new mutation, dramatically shrinks aggressive sarcoma and lung cancer
(Date:4/28/2016)... ... April 28, 2016 , ... The Dentists ... it has signed a letter of intent with Moda to acquire ... Company (NORDIC). , Started by dentists 36 years ago, TDIC focuses exclusively on ...
(Date:4/28/2016)... ... April 28, 2016 , ... Sanford Health’s work ... A group of researchers and leaders from Sanford Health were selected to participate ... Its Cultural Impact ” and receive the 2016 Pontifical Key Innovation Award at ...
(Date:4/28/2016)... ... April 28, 2016 , ... ProText Layouts is a set ... Pro X . With ProText Layouts, video editors can create an energetic typography ... length and scale of texts. Creating text-based videos have never been easier. , ...
(Date:4/28/2016)... ... April 28, 2016 , ... La Sirena Foods provides ... in Central America and is looking to grow their market share in the USA. ... exceptional brand as La Sirena Foods and indirectly with Otis McAllister ...
(Date:4/28/2016)... California (PRWEB) , ... April 28, 2016 , ... ... and accessories, is proud to partner with AquaShieldUSA, the country's oldest waterproof ... patient, clinic and medical supply stores, the largest selection of daily, night, weatherproof ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)...   Click here for supplemental information regarding ... the nation,s largest independent specialty pharmacy, announced today ... acquire Valley Campus Pharmacy, Inc., doing business as ... pharmacy that provides individualized patient care, based in ... 2015, TNH generated approximately $400 million in revenue. ...
(Date:4/28/2016)... 2016  While Abbott,s announced purchase of St. ... repair and stent business, healthcare research firm Kalorama ... firmly into patient monitoring.  Kalorama said that patient ... areas, with double-digit growth expected the next 5 ... Remote Patient Monitoring . Abbott Laboratories agreed ...
(Date:4/28/2016)... 28, 2016 Research and Markets ... Surgery Products Market 2016-2020" report to their offering. ... The global plastic surgery products market is ... the period 2016-2020. , ,The growing adoption of laser ... growth of the market. Lasers are used to treat ...
Breaking Medicine Technology: