Filling the gap between chemical carcinogenesis and the hallmarks of cancer: A temporal perspective

Demetriou, Christiana A.; Esposti, Davide Degli; Fedinick, Kristi Pullen; Russo, Federico; Robinson, Oliver; Víneis, Paolo

doi:10.1111/eci.12933

Cited by 10 publications

(2 citation statements)

References 69 publications

(113 reference statements)

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“…A recent study by Demetriou and others (Demetriou, Degli Esposti et al 2018) discusses the temporal sequence of acquisition of hallmarks of cancer in the course of exposure to chemical carcinogens, based on mutations in biopsies. Radiation is much more complex in its effects than chemical mutagens and it modulates all hallmarks of cancer, with different doses and radiation delivery approaches often having contradictory effects – sometimes supporting and sometimes opposing cancer growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Reflections on Basic Science Studies Involving Low Doses of Ionizing Radiation

Paunesku¹,

Woloschak²

2018

Health Physics

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Investigation of health effects of low doses of radiation as a field of study has been riddled with difficulties since its inception. In this document we will use 100 mGy as the cutoff upper limit for low-dose radiation, borrowing this definition from the U.S. Department of Energy, although other agencies and researchers sometimes include up to five‐fold higher doses under the same title. Difficulties in this area of research are most often ascribed to the fact that effects of low doses of radiation are subtle and difficult to distinguish from the plethora of other low-grade stresses. Thus, for example, most epidemiological studies include hundreds of thousands of samples and generate risk estimates that are statistically meaningful only when they are considered on a scale of hundreds or thousands of people. A logical approach to remedy the situation for low-dose research was to conduct well-controlled animal studies with hundreds of animals; nevertheless, even after many such studies were completed, our understanding of the biological basis for risk from low-dose radiation exposure is still not conclusive. In this paper we argue that the problem lies in the fact that our approach to animal studies is not comprehensive but conceptually binary. While some researchers apply epidemiological models to animal data, others look into molecular and cellular biology only. Very few studies are conducted to bridge this gap and consider how a realistic model of DNA damage could be integrated into a realistic model of radiation carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Reflections on Basic Science Studies Involving Low Doses of Ionizing Radiation

Paunesku¹,

Woloschak²

2018

Health Physics

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“…Whereas selected chemicals may target specific cancer sites, the chemical screening approach is cancer-site agnostic and relies on the common features of carcinogenesis. For example, Demetriou et al (2018) analyzed biopsies from different cancer sites and proposed a temporal sequence for the acquisition of the hallmarks of cancer in which cancer unfolds in a generally common sequence with resisting cell death, insensitivity to antigrowth signals, and sustained proliferation occurring first (nearly simultaneously), followed by deregulated energetics, replicative immortality, and the activation of invasion and metastasis. They further noted that angiogenesis and avoiding immune destruction were hallmarks that could appear at varying steps in this common sequence (Demetriou et al 2018).…”

Section: Chemical Screening Approachmentioning

confidence: 99%

Using the Key Characteristics of Carcinogens to Develop Research on Chemical Mixtures and Cancer

Rider

McHale

Webster

et al. 2021

Environ Health Perspect

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BACKGROUND: People are exposed to numerous chemicals throughout their lifetimes. Many of these chemicals display one or more of the key characteristics of carcinogens or interact with processes described in the hallmarks of cancer. Therefore, evaluating the effects of chemical mixtures on cancer development is an important pursuit. Challenges involved in designing research studies to evaluate the joint action of chemicals on cancer risk include the time taken to perform the experiments because of the long latency and choosing an appropriate experimental design. OBJECTIVES: The objectives of this work are to present the case for developing a research program on mixtures of environmental chemicals and cancer risk and describe recommended approaches. METHODS: A working group comprising the coauthors focused attention on the design of mixtures studies to inform cancer risk assessment as part of a larger effort to refine the key characteristics of carcinogens and explore their application. Working group members reviewed the key characteristics of carcinogens, hallmarks of cancer, and mixtures research for other disease end points. The group discussed options for developing tractable projects to evaluate the joint effects of environmental chemicals on cancer development. RESULTS AND DISCUSSION: Three approaches for developing a research program to evaluate the effects of mixtures on cancer development were proposed: a chemical screening approach, a transgenic model-based approach, and a disease-centered approach. Advantages and disadvantages of each are discussed.

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