Introduction to Cancer
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Neutrons (which are particles rather than γ- or X-rays) are also used in cancer therapy (see Chapter 10). For example, a process known as high linear energy transfer has been developed to kill hypoxic cells by irradiating the tumor with neutrons that then decay to α-particles, the latter causing cellular damage in an oxygen-independent manner. A more sophisticated treatment known as boron neutron capture therapy involves administration of a boron-10 (10B)–enriched delivery agent that is taken up selectively by the tumor. The target area is then irradiated with low energy neutrons that are captured by the 10B atoms, thus leading to a reaction that produces α–particles (4He) and lithium-7 (7Li) ions that destroy the tumor tissue.
Immunoglobulins
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Many attempts have been made to endow mAbs with the ability to destroy the cells to which they bind. Several strategies have been employed: high specific activity radiolabelling; coupling to standard cytotoxic chemotherapeutic agents; and coupling to exotoxins of plant or bacterial origin. Each of these methods has had varying success, in several instances impressive tumor remissions have been documented. Cytotoxic mAbs are also being used to purge tumor cells from autologous bone marrow transplants (see Figure 2–11), or to eliminate mature T cells from allogeneic transplants and prevent graft-versushost disease (see Chapter 8). In the technique of boron-neutron-capture-therapy, boron atoms are linked to a tumor-specific mAb. The antibody is infused, and external radiation is directed at the site of the tumor. When low-energy neutrons strike boron nuclei, an alpha particle is emitted. These are relatively large and slow particles which damage macromolecules in a very restricted area. Continued refinement of these techniques will doubtless yield powerful adjuncts to current management protocols.
Medical and Biological Applications of Low Energy Accelerators
Vlado Valković in Low Energy Particle Accelerator-Based Technologies and Their Applications, 2022
It is likely that, unless dramatic progress is made in cancer prevention or cure, radiotherapy (i.e., the selective destruction of cancer tissues by the use of ionizing radiations) will remain one of the pillars in cancer therapy. The most common irradiation facilities in hospitals nowadays are still 60Co sources and electron accelerators (e.g., Japan has more than 620 linear electron accelerators devoted to medical applications). However, among the possible radiations usable in radiotherapy (X-rays, γ-rays, electrons, protons, heavy ions, π-mesons and neutrons) it is generally agreed that high-energy protons exhibit the best ballistic specificity, i.e., the best ratio of the dose delivered into the tumor, compared to the dose delivered to neighboring tissues. Particle therapy is being applied at more than twenty locations around the globe. Neutron therapy has also been performed for many years and the new hope is with boron neutron capture therapy (BNCT) in which a tumor is loaded with a boron-dope compound and then irradiated by epithermal neutrons.
Research progress on therapeutic targeting of quiescent cancer cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Jinhua Zhang, Jing Si, Lu Gan, Cuixia Di, Yi Xie, Chao Sun, Hongyan Li, Menghuan Guo, Hong Zhang
Boron neutron capture therapy (BNCT) is a novel targeted radiotherapy that selectively kills tumor cells. After introduction into the human body, Boron (10B) is enriched in tumor cells and reacts with neutrons. The reaction generates high LET α particles (4He) and recoiling 7Li nuclei, which result in the induction of DSBs with strong biological effectiveness. Since the path lengths of these particles are almost equal to cell diameter size, only 10B-containing cancer cells are theoretically destroyed without causing serious radiation injury to surrounding normal tissue [92,93]. The cellular distribution of 10B from L-para-boronophenylalanine-10B (BPA) is believed to be largely dependent on the capability of the cells to take up 10B whereas that from sodium mercaptoundecahydrododecaborate-10B (BSH) mainly relies on drug diffusion [11]. Importantly, the use of a 10B-carrier in BNCT, especially BPA, not only effectively eliminates hypoxia and quiescent cells but also kills oxygenated and proliferative cells [11,94].
No time to die – BiGART is back. The 20th Acta Oncologica Symposium – BIGART 2021
Published in Acta Oncologica, 2022
Morten Høyer, Cai Grau, Jens Overgaard
During the most recent years, the integrated MRI-linac has been introduced and MRI-linacs are now being installed in oncology centers around Europe and North America. In the Nordic countries four of these have been commissioned and are now in clinical operation. Improved soft-tissue resolution combined with a modern IT platform allow accurate patient set-up and online treatment plan adaptation to compensate for day-to-day anatomical changes. On the backside, the MRI-linac demands specific and resource demanding work-flow with long treatment times with physicians and physicists on the spot during the treatment sessions and it is not straight forward to define what are the clinical indications for the MRI-linac [12,13]. Other emerging technologies are also being explored, such as a new center for accelerator-based Boron Neutron Capture Therapy (BNCT) in Helsinki [14], and all in all, the Nordic countries have globally become the region with the most high technological radiation facilities per capita, and consequential research activity [15–18]. This leaves immense possibilities for therapeutic improvements, and a strong obligation to scientifically explore and disseminate the potentials of such technology. The BiGART meeting are one of the ways to solve the latter issue.
Roles of homologous recombination in response to ionizing radiation-induced DNA damage
Published in International Journal of Radiation Biology, 2023
Jac A. Nickoloff, Neelam Sharma, Christopher P. Allen, Lynn Taylor, Sage J. Allen, Aruna S. Jaiswal, Robert Hromas
Ionizing radiation comprises high-energy photons (X- and γ-rays) and charged particles, including protons and ions with greater mass and charge, such as carbon and iron ions. At present, many solid tumors are treated with X-rays, protons, and carbon ions in mono- or combination therapies (Halperin et al. 2018), although early studies suggest other intermediate mass/charge particles have potential therapeutic value, including neon and oxygen (Linstadt et al. 1991; Sokol et al. 2017). Fast neutrons are also used in therapeutic applications, but neutrons are more difficult to focus than charged particles, and shielding poses significant challenges, severely limiting its use in clinical practice. Currently, neutrons are largely being explored in boron-neutron capture therapy (Moss 2014). Regardless of how ionizing radiation is delivered, its cell-killing effects are due to cellular damage caused by direct energy absorption and to a greater extent, to indirect effects of reactive oxygen species (ROS) such as hydroxyl radicals produced by ionization of water (Azzam et al. 2012), although secondary ROS produced by mitochondria are also induced by ionizing radiation (Yoshino and Kashiwakura 2017). In terms of cell killing, the most important target for ionizing radiation and ROS is DNA, and these events result in a wide variety of DNA lesions including oxidative damage, ring-opened bases, and single-strand breaks (collectively termed single-strand damage), and double-strand breaks (DSBs) (Ward 2000). DSBs have long been the lesion of interest in radiobiology and radiation oncology because DSBs, along with intra-strand DNA crosslinks, are the most cytotoxic DNA lesions. These general features of ionizing radiation damage to DNA are summarized in Figure 1.
Related Knowledge Centers
- Alpha Particle
- Boron
- Brain Tumor
- Gadolinium
- Gamma Ray
- Head & Neck Cancer
- Linear Energy Transfer
- Phenylalanine
- Glioma
- Radiation Therapy
- Head & Neck Cancer