ASCO
NEWS OF THE WEEK
TARGETED DRUGS GET TRACTION PHARMACEUTICALS: Drug firms announce advances in personalized medicine at oncologists’ meeting
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LTHOUGH NO MAJOR breakthroughs in cancer
treatment were announced at the annual meeting of the American Society of Clinical Oncology (ASCO), held last week in Orlando, Fla., patients still got plenty of good news. On the basis of early results from a number of clinical trials using biomarkers and genetics to identify patients, drug companies finally appear to be harnessing the potential of personalized medicine. “We believe it could be remembered as a landmark conference for molecularly targeted therapy,” says Howard Liang, a stock analyst at Leerink Swann who covers the drug industry. He notes that drug companies are getting better at figuring out which cancer patients have the genetic makeup to benefit from their drugs and then designing clinical trials accordingly. Lung cancer, in particular, is becoming an increasingly “genotypical disease,” Liang says. At the meeting, AstraZeneca unveiled data suggesting its lung cancer pill Iressa is highly effective at shrinking tumors in a small
More than 25,000 oncologists, cancer researchers, and cancer care professionals attended the ASCO meeting.
PALLADIUM(III) DEBUT ORGANOMETALLIC CHEMISTRY:
Pd(III) complexes are actors on the catalysis stage
Bimetallic Pd(III) complex, as shown in an X-ray structure.
F Cl
N
N
Pd
Pd Cl
OR THE FIRST TIME, chemists have demonstrat-
ed that palladium complexes in the +3 oxidation state are intermediates in catalytic bond-forming processes. This finding puts a new twist on the chemistry of palladium and could someday lead to new reactions. Palladium catalyzes a wide variety of reactions, and the chemistry of its oxidation states of 0, +1, +2, and +4 is well-known. Graduate student David C. Powers and assistant professor of chemistry Tobias Ritter of Harvard University made O the new discovery while investigating the mechanism of a small set of Pd-catalyzed O carbon-heteroatom bond-forming reactions. These types of reactions have been O thought to always proceed via a catalytic O cycle that switches between Pd(II) and Pd(IV), where a lone Pd metal center gives up two electrons to form the new bond. WWW.CEN-ONLINE.ORG
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portion of the population. The company launched Iressa under FDA’s accelerated approval program in 2003, but the agency limited its use in 2005 after a larger trial showed the drug did not help patients live longer. The new study shows that Iressa works for Asians who have been nonsmokers or light smokers and have a mutation in the epithelial growth-factor receptor gene. Pfizer revealed at ASCO that it has identified a subset of patients who will benefit most from its lung cancer drug candidate figitumumab. The anti-insulin growth factor-type 1 (IGF-1) receptor antibody, now in Phase III studies, appears to work best when added to the chemotherapy regimen of patients with high levels of free IGF-1 in their plasma. Pfizer is exploring additional biomarkers to help determine which other patients will be most sensitive to figitumumab. Meanwhile, Merck & Co. and AstraZeneca are teaming up to study how different protein targets interact in certain cancer pathways. At ASCO, the companies announced a unique collaboration to study the merits of giving two protein-targeting drug candidates, the MEK inhibitor AZD6244 and the AKT inhibitor MK2206, in combination for solid tumors. Often, both the MEK and AKT pathways are turned on in these tumors, and the companies believe blocking both proteins would improve and prolong the efficacy of the drugs. Merck and AstraZeneca will jointly launch a Phase I trial to study the benefit of coadministering the compounds.—LISA JARVIS
On the basis of kinetic experiments, they instead propose that complexes containing two Pd(III) metal centers are intermediates in the reactions, with each Pd contributing one electron to a nascent C-heteroatom bond (Nat. Chem., DOI: 10.1038/nchem.246). It’s not certain that the newly discovered mechanism will prove to be generally applicable, but Ritter’s team hopes to explore the bimetallic Pd(III) catalyst’s potential in a variety of reactions. Nature makes use of bimetallic catalysis in a variety of enzyme active sites, and bimetallic catalysts made from rhodium, palladium’s next-door neighbor on the periodic table, are versatile tools for synthesis, Ritter notes. The team “has provided a timely and fascinating contribution to the current rapid development of higher oxidation state organopalladium chemistry and a stimulating evaluation of the potential involvement of such states in organic synthesis,” says Allan J. Canty of the University of Tasmania, in Australia. Canty recently showed that analogous platinum(III) complexes can serve as reaction intermediates (J. Am. Chem. Soc. 2009, 131, 7236). The advance builds on work by the late F. Albert Cotton of Texas A&M University, who first demonstrated that these types of Pd(III) complexes could be made in the laboratory, says organometallic chemist Melanie S. Sanford of the University of Michigan.—CARMEN DRAHL
JUNE 8, 2009
