Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Data from: Latitudinal patterns of herbivore pressure in a temperate herb support the biotic interactions hypothesis

The longstanding biotic interactions hypothesis predicts that herbivore pressure declines with latitude, but the evidence is mixed. To address gaps in previous studies, we measured herbivory and defense in the same system, quantified defense with bioassays, and considered effects of leaf age. We quantified herbivory and defense of young and mature leaves along a continental gradient in eastern North America in the native herb Phytolacca americana. Herbivory in the field declined with latitude and was strongly correlated with Lepidopteran abundance. Laboratory bioassays revealed that leaf palatability was positively correlated with latitude of origin. Young leaves were more damaged than mature leaves at lower latitudes in the field, but less palatable in bioassays. Both defense and palatability displayed non-linear latitudinal patterns, suggesting potential mechanisms based on biological or climatic thresholds. In sum, observational and experimental studies find patterns consistent with high herbivore pressure and stronger plant defenses at lower latitudes