Linking the History of Radiation Biology to the Hallmarks of Cancer

Abstract

Hanahan and Weinberg recently updated their conceptual framework of the “Hallmarks of Cancer”. The original article, published in 2000, is among the most highly cited reviews in the field of oncology. The goal of this review is to highlight important discoveries in radiation biology that pertain to the Hallmarks. We identified early studies that exemplified how ionizing radiation affects the hallmarks or how radiation was used experimentally to advance the understanding of key hallmarks. A literature search was performed to obtain relevant primary research, and topics were assigned to a particular hallmark to allow an organized, chronological account of the radiobiological advancements. The hallmarks are reviewed in an order that flows from cellular to microenvironmental effects.

Effects of radiation on metastasis and tumor cell migration

“…This dose-dependent up-regulation occurs between 24 hours and 1 week after radiation exposure, possibly caused by free radical species produced upon irradiation as well as the depolymerization of stress granules [38–40]. As a consequence, several important downstream targets of HIF-1 are upregulated in irradiated tumors, which may contribute to increased metastasis [31, 41, 42]. The increased fraction of hypoxic cells observed upon recurrence after RT suggests that targeted inhibition of HIF-1 after radiotherapy may improve tumor control, however the potential impact of this inhibition remains controversial due to the complexity of the HIF-1 signaling pathway [31, 39, 43].…”

Toxicogenetic biomonitoring of occupational risk induced by ionizing radiation

“…It is well established that IR induce instability in chromosomes and have effects on activation and inactivation of DNA repair mechanisms, induce oxidative damage, but is not yet well established role of IR on telomeric proteins, which are considered to be protective of genome and related to carcinogenesis (Shim et al, 2014). Numerous effects of radiation have been identified in association with mutations and genomic instability (breaks and actions in repair genes), angiogenesis (vascularisation and hypoxia), apoptosis (changes in p53), proliferative signaling (EGCR and TGF-α), suppression of cell cycle (ATM, p53 lock), energy dysregulation (HIF, c-MyC, glycolytic pathways inhibitors), tumor promotion and inflammation (p53 and ROS) and activation and inactivation of metastases (hypoxia, lactate) (Boss et al, 2014). Given the risks of cancer, studies suggest biological dosimeters guided by genetic instability mechanisms, is noted in summary in Table 3, especially for chromo-somal aberrations that may be markers for evaluation of dose and biological effects induced by IR (Higueras et al, 2015).…”

“…Given the risks of cancer, studies suggest biological dosimeters guided by genetic instability mechanisms, is noted in summary in Table 3, especially for chromo-somal aberrations that may be markers for evaluation of dose and biological effects induced by IR (Higueras et al, 2015). Numerous effects of radiation (Table 3) have been identified in association with mutations and genomic instability (breaks and actions in repair genes), angiogenesis (vascularization and hypoxia), apoptosis (changes in p53), proliferative signaling (EGCR and TGF-α), suppression of cell cycle (ATM, locking p53), energy deregulation (HIF, c-MyC, glycolytic pathways inhibitors), tumor promotion and inflammation (p53 and ROS) and activation and inactivation of metastases (hypoxia, lactate) (Boss et al, 2014;Lee et al, 2014). Relation among age, gender, DNA damage and cytotoxicity.…”

“…High and low doses Shim et al (2014) Mutations and genomic instability. Angiogenesis, apoptosis, proliferation, energy imbalance, inflammation and metastases High and low doses Boss et al (2014) Figure 3. Mutagenicity (A) and apoptotic DNA fragmentation (B) according to tertis of age in buccal mucosa cells from workes exposed to ionizing radiation and control group.…”

Radiation protection biology then and now

“…A number of excellent reviews describing achievements and developments in radiation biology have been published in recent years (Bedford and Dewey 2002;Preston 2004;Boss et al 2014;Streffer 2015;Nakamura 2019), so what new insights are presented in the current review? Our approach was not to summarize scientific achievements in the field of radiation biology but to highlight research carried out in the context of radiological protection of people.…”