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A way forward for cancer prevention therapy: personalized risk assessment.

ABSTRACT: Cancer is characterized by genetic and molecular aberrations whose number and complexity increase dramatically as cells progress along the spectrum of carcinogenesis. The pharmacologic application of agents in the context of a lower burden of dysregulated cellular processes constitutes an efficient strategy to enhance therapeutic efficacy, and underlies the rationale for using cancer prevention agents in high-risk populations. A longstanding barrier to implementing this strategy is that the risk in the general population is low for any given cancer, many people would have to be treated in order to benefit a few. Therefore, identifying and treating high-risk individuals will improve the risk: benefit ratio. Currently, risk is defined by considering a relatively low number of factors. A strategy that considers multiple factors has the ability to define a much-higher-risk cohort than the general population. This article will review the rationale for evaluating multiple risk factors so as to identify individuals at highest risk. It will use breast and lung cancer as examples, will describe currently available risk assessment tools, and will discuss ongoing efforts to expand the impact of this approach. The high potential of this strategy to provide a way forward for developing cancer prevention therapy will be highlighted.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC6901339 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A way forward for cancer prevention therapy: personalized risk assessment.

Zhang Zhenzhen Z Bien Jeffrey J Mori Motomi M Jindal Sonali S Bergan Raymond R

Oncotarget 20191203 64

Cancer is characterized by genetic and molecular aberrations whose number and complexity increase dramatically as cells progress along the spectrum of carcinogenesis. The pharmacologic application of agents in the context of a lower burden of dysregulated cellular processes constitutes an efficient strategy to enhance therapeutic efficacy, and underlies the rationale for using cancer prevention agents in high-risk populations. A longstanding barrier to implementing this strategy is that the risk ...[more]

PMID: 31839883

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Project description:BackgroundThe COVID-19 pandemic shows that the impact of effective vaccines can extend well beyond vaccinated individuals and healthcare systems. Yet, these broader value elements are not typically considered in Health Technology Assessment (HTA) which may underestimate vaccines' broader value.ObjectivesThis study aimed to (1) describe the gap between broader value elements identified in value frameworks for vaccines and those recognised in HTA of vaccines in nine developed markets, and (2) develop expert-informed, consensus-based recommendations on how hurdles for broader value recognition could be overcome.MethodsWe used a four-step modified Delphi method consisting of literature research (phase I, pearl-growing approach using PubMed Web of Science and Google covering the years 2000-2019), two consecutive phases of expert elicitation (phase II and III, including two email surveys and one virtual round table with 10 experts from 9 countries) and synthesis of recommendations (phase IV).ResultsResults show that about half of the broader value elements relevant to vaccines are not (consistently) considered in HTA processes of multiple higher-income countries. Experts identified five priority areas for broader value recognition, including considering (1) more comprehensive cost offsets within the health care system, (2) carer quality of life, (3) transmission value, (4) prevention of antimicrobial resistance and (5) macroeconomic effects.ConclusionTo achieve a broader recognition of the value of vaccines, a three-pronged approach was recommended, focusing on (1) Evidence: proactively steering generation of high-quality evidence to quantify the broader value of vaccines to society; (2) Ability: leveraging and further developing existing methodological and analytic expertise to appropriately recognise the broad value of vaccines within HTA processes; (3) Willingness: Stimulating stakeholder engagement to change the status quo and move towards more transparent and comprehensive value assessment processes for vaccines globally.

Project description:The OBIS-SEAMAP project has acquired and served high-quality marine mammal, seabird, and sea turtle data to the public since its inception in 2002. As data accumulated, spatial and temporal biases resulted and a comprehensive gap analysis was needed in order to assess coverage to direct data acquisition for the OBIS-SEAMAP project and for taxa researchers should true gaps in knowledge exist. All datasets published on OBIS-SEAMAP up to February 2009 were summarized spatially and temporally. Seabirds comprised the greatest number of records, compared to the other two taxa, and most records were from shipboard surveys, compared to the other three platforms. Many of the point observations and polyline tracklines were located in northern and central Atlantic and the northeastern and central-eastern Pacific. The Southern Hemisphere generally had the lowest representation of data, with the least number of records in the southern Atlantic and western Pacific regions. Temporally, records of observations for all taxa were the lowest in fall although the number of animals sighted was lowest in the winter. Oceanographic coverage of observations varied by platform for each taxa, which showed that using two or more platforms represented habitat ranges better than using only one alone. Accessible and published datasets not already incorporated do exist within spatial and temporal gaps identified. Other related open-source data portals also contain data that fill gaps, emphasizing the importance of dedicated data exchange. Temporal and spatial gaps were mostly a result of data acquisition effort, development of regional partnerships and collaborations, and ease of field data collection. Future directions should include fostering partnerships with researchers in the Southern Hemisphere while targeting datasets containing species with limited representation. These results can facilitate prioritizing datasets needed to be represented and for planning research for true gaps in space and time.

Project description:Simple Summary Cells need to produce ribosomes to sustain continuous proliferation and expand in numbers, a feature that is even more prominent in uncontrollably proliferating cancer cells. Certain cancer cell types are expected to depend more on ribosome biogenesis based on their genetic background, and this potential vulnerability can be exploited in designing effective, targeted cancer therapies. This review provides information on anti-cancer molecules that target the ribosome biogenesis machinery and indicates avenues for future research. Abstract Rapid growth and unrestrained proliferation is a hallmark of many cancers. To accomplish this, cancer cells re-wire and increase their biosynthetic and metabolic activities, including ribosome biogenesis (RiBi), a complex, highly energy-consuming process. Several chemotherapeutic agents used in the clinic impair this process by interfering with the transcription of ribosomal RNA (rRNA) in the nucleolus through the blockade of RNA polymerase I or by limiting the nucleotide building blocks of RNA, thereby ultimately preventing the synthesis of new ribosomes. Perturbations in RiBi activate nucleolar stress response pathways, including those controlled by p53. While compounds such as actinomycin D and oxaliplatin effectively disrupt RiBi, there is an ongoing effort to improve the specificity further and find new potent RiBi-targeting compounds with improved pharmacological characteristics. A few recently identified inhibitors have also become popular as research tools, facilitating our advances in understanding RiBi. Here we provide a comprehensive overview of the various compounds targeting RiBi, their mechanism of action, and potential use in cancer therapy. We discuss screening strategies, drug repurposing, and common problems with compound specificity and mechanisms of action. Finally, emerging paths to discovery and avenues for the development of potential biomarkers predictive of therapeutic outcomes across cancer subtypes are also presented.

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A way forward for cancer prevention therapy: personalized risk assessment.

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A way forward for cancer prevention therapy: personalized risk assessment.

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