New Targets, Techniques Excite Cancer Researchers

Editor's Note: In this issue, The Scientist focuses on the status of cancer research in the United States. The articles below and on pages 6-9 present glimpses of the latest advances. The article beginning at right describes how cancer and AIDS research are related. The article on page 10 offers a look at thyroid cancer treatments from the perspectives of patient and scientist. Commentary (12) and Opinion (13) are by prominent cancer experts. Profession (14-15) assesses the outlook for cancer research careers. Hot Papers (16) offers a discussion on cancer statistics. And Notebook (31) has even more cancer research news. A long with an alphabet soup of oncogene and tumor suppressor names, presenters frequently uttered the word "exciting" during a series of recent cancer conferences. The reason for this optimism among a group of researchers normally known for their reserve? "There's a whole new variety of targets ... and new techniques [to attack them]," Serge Lichtsteiner, of Menlo Park, Calif.-based Geron Corp., said in an interview during a break in a New York Academy of Sciences-sponsored cancer conference. Targets whose profiles continue to grow include the gene p53, the enzyme telomerase, and DNA repair mechanisms. And therapeutic advances include potential small-molecule inhibitors of tumor-suppressor pathways, synthetic and natural regulators of gene expression, and continued development in gene therapy and antisense techniques. Peter Traxler of the Novartis Department of Oncology Research in Basel, Switzerland, agrees with the excitement assessment. But he cautions that an abundance of targets doesn't automatically guarantee success: "It will still be difficult to identify the good targets." And newer techniques--although they sound promising--face many obstacles, too, Traxler adds, noting that large pharmaceuticals will likely stick with small molecules until other, smaller companies prove the efficacy of emerging techniques. "With small molecules, it is easier to get into the target," Traxler maintains. "Normally, with proteins and with antisense, you are faced with the problem of delivery. And that's probably not changing." During his New York Academy of Sciences talk on delivering a functional retinoblastoma (Rb) gene back into mice through gene therapy, Wen-Hwa Lee, a University of Texas Southwestern Medical Center researcher, alluded to the difficulty of dealing with so many targets. The adenoviral vector he and colleagues used successfully "rescued" the mice, but since the gene regulates an earlier part of the apoptotic pathway than p53 regulates, it may not be ideal. "Because p53 takes care of most kinds of cancer, Rb may not be necessary," Lee commented. Interactions between major cancer-related pathways such as Rb, p53, and the gene Ras will become more clearly defined, Frank McCormick, founder of Onyx Pharmaceuticals Inc., of Richmond, Calif., and director of the University of California at San Francisco's cancer center, predicted during an interview at the New York meeting. He added that while the identities of these pathways have been known for some time, their intricacies have not. "It was known that the Ras pathway [was important], p53 was important, and Rb was important. The way they all fit together wasn't clear," McCormick states. That is changing--and adding to the atmosphere of cautious optimism among cancer researchers. "The more you get into the details on each of these pathways, the more targets you'll reveal." McCormick also predicts that, ultimately, genomics may well divide cancers--and related cancer-fighting strategies--into two categories. "If you take all the mutations that cause cancer, maybe 50 percent of them are in these common themes and perhaps 50 percent are cancer-specific." The future of treatment may well include trying to fix one of these general problems, such as restoring p53 function, as well as repairing more tumor-specific mutations.

New Targets, Techniques Excite Cancer Researchers

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