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- Block, Keith I., et al.
(author)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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In: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Research review (peer-reviewed)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships 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. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 2. |
- Stagg, Anne L., et al.
(author)
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Risk factors for the progression to multimorbidity among UK urban working-age adults. A community cohort study
- 2023
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In: PLOS ONE. - 1932-6203. ; 18:9
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Journal article (peer-reviewed)abstract
- ObjectivesThe progression of long-term conditions (LTCs) from zero-to-one (initiation), and from one-to-many (progression)are common trajectories that impact a person’s quality of life including their ability to work. This study aimed to explore the demographic, socioeconomic, psychosocial, and health-related determinants of LTC initiation and progression, with a focus on work participation.MethodsData from 622 working-age adults who had completed two waves (baseline and follow-up) of the South-East London Community Health survey were analysed. Chi square tests and multinomial logistic regression were used to describe the associations between self-reported demographic, socioeconomic, psychosocial, and health-related variables, and the progression of LTCs.ResultsSmall social networks, an increased number of stressful life events, low self-rated health, functional impairment, and increased somatic symptom severity were all associated with both the progression from zero-to-one LTC and from one LTC to multimorbidity (two or more LTCs). Renting accommodation (RRR 1.73 [95% CI 1.03–2.90]), smoking (RRR 1.91 [95% CI 1.16–3.14]) and being overweight (RRR 1.88 [95% CL 1.12–3.16]) were unique risk factors of developing initial LTCs, whereas low income (RRR 2.53 [95% CI 1.11–5.80]), working part-time (RRR 2.82 ([95% CL 1.12–7.10]), being unemployed (RRR 4.83 [95% CI 1.69–13.84]), and making an early work exit (RRR 16.86 [95% CI 3.99–71.30]) all increased the risk of progressing from one LTC to multimorbidity compared to being employed full-time. At follow-up, depression was the most prevalent LTC in the unemployed group whereas musculoskeletal conditions were the most prevalent in those working.ConclusionsThe journey to multimorbidity is complex, with both common and unique risk factors. Non-full-time employment was associated with an increased risk of progression to multimorbidity. Future research should explore the risk and benefit pathways between employment and progression of LTCs. Interventions to prevent progression of LTCs should include mitigation of modifiable risk factors such as social isolation.
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