ANDRZEJ KRAUZEIn the arcade game Whac-a-Mole, which debuted in 1976, the player clobbers a randomly appearing plastic mole with a large rubber mallet. If the mole’s head isn’t hit hard enough, no score. The game seems like an apt metaphor for what clinicians face when dealing with the problem of biological persisters, be they cancer cells that have survived surgery and chemotherapy or bacteria that have withstood an antibiotic onslaught: merely knocking them over the head may not be enough to eliminate the offenders. As a result, researchers are now trading in that large rubber mallet for much more subtle and cleverly designed weapons.
Definitively eliminating cancer cells is difficult because of their heterogeneity and the ease with which they evolve resistance to chemotherapeutic drugs. Knowledge of the molecular pathways altered in tumor cells, coupled with a wealth of genetic sequencing data from individual patients’ changing cancer profiles, has led to the design of new chemotherapy regimens that are more rational and personalized. But another challenge in fighting cancer is its ability to evade attack by the body’s immune system. The idea of boosting a patient’s immune response to fight his cancer has long been touted as an exquisitely sensitive attack strategy, but only in the last few years has clinical development of such therapies begun to soar. In this issue of The Scientist, Jamie Green and Charlotte Ariyan describe the burgeoning field of cancer immunotherapy (here), designated 2013’s Breakthrough of the Year by Science magazine. Techniques include the deployment of specially designed cancer vaccines, the blockading of mechanisms that normally dampen the body’s response to pathogens, and the engineering of a patient’s own T cells to attack her cancer upon reinfusion. In a Profile (here), one of the field’s pioneers, Carl June, talks about some of his spectacular successes using this latter attack strategy.
Other related articles included in our annual focus on cancer discuss methods for spotting and characterizing circulating tumor cells (here); the heterogeneity of stem cells in breast cancer tumors (here); and the role that nanomedicine is poised to play in delivering cancer therapeutics that are more effective and less toxic (here).
Molecular knowledge breeds smarter, more precise therapies.
Infections caused by antibiotic-resistant bacteria—and their really sneaky persister forms, which go dormant to evade attack—are an enormous and growing challenge, costing the US health-care system more than $20 billion each year. The last time a new class of antibiotics hit the market was the lipopeptides in 2003. To chart what’s happening in the field, The Scientist staff reports on four new strategies for fatally whacking resistant pathogens: chemically altering old antibiotics to make them more effective; treating with a combination of different drugs; adding adjuvants to existing antibiotics; and searching for new and effective antimicrobials in Earth’s living landscape, from insects to plants.
With Alzheimer’s disease (AD), knowing what target(s) to whack remains maddeningly elusive. AD’s enormous and rapidly growing cost to society is driving research on many different fronts, especially early detection based on biomarker levels that rise or fall as the disease progresses. But what actually initiates the changes associated with the disease has yet to be figured out. In “Metals on Our Mind,” Anthony White describes the central role that dysregulation in copper distribution in neuronal cells may play during the onset of the disease and discusses some therapies aimed at correcting the problem.
Precision-targeted weapons more akin to heat-seeking missiles are clearly replacing the rubber mallets in the clinician’s armory.
Mary Beth Aberlin Editor-in-Chief firstname.lastname@example.org