Abstract
Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.
Highlights
Cancer is a disease of uncontrolled cellular proliferation, leading to unfaithful and uncoordinated DNA replication, genomic instability, and DNA double-strand breaks (DSBs)
12C ions are the optimal ion for treating deep-seated tumors, because the higher relative biological effectiveness (RBE) resulting from variations in linear energy transfer (LET) along the ion path can be limited to the tumor volume with minimal normal tissue injury along the entrance track
Technological advancements have fueled the development of sophisticated machines capable of delivering ionizing radiation precisely to tumors, but the fundamental mechanisms by which Radiation therapy (RT) kills tumor cells are independent of the technique used for radiation delivery
Summary
Cancer is a disease of uncontrolled cellular proliferation, leading to unfaithful and uncoordinated DNA replication, genomic instability, and DNA double-strand breaks (DSBs). Cancer cells often exhibit defects in the DNA repair mechanism that drive genomic instability, thereby fueling further tumorigenesis. These defects in DNA repair can be exploited by inhibitors that target the remaining DNA repair pathways that the cancer cells rely upon more heavily, because of the loss of other repair factors and because of the higher load of overall DNA damage in cancer cells. PT clinical practice uses proton or Carbon-ion (12C) beams, other light ion beams, such as Helium, Oxygen, and Neon, have been investigated [2,3,4] These particles each have their own physical and biological advantages. To fully exploit the clinical potential of RT-induced antitumor immunity while avoiding immunosuppression, we need to understand the radiobiology and the underlying mechanisms of immunomodulatory effects of RT
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