Hadrontherapy Interactions in Molecular and Cellular Biology

Abstract

The resistance of cancer cells to radiotherapy is a major issue in the curative treatment of cancer patients. This resistance can be intrinsic or acquired after irradiation and has various definitions, depending on the endpoint that is chosen in assessing the response to radiation. This phenomenon might be strengthened by the radiosensitivity of surrounding healthy tissues. Sensitive organs near the tumor that is to be treated can be affected by direct irradiation or experience nontargeted reactions, leading to early or late effects that disrupt the quality of life of patients. For several decades, new modalities of irradiation that involve accelerated particles have been available, such as proton therapy and carbon therapy, raising the possibility of specifically targeting the tumor volume. The goal of this review is to examine the up-to-date radiobiological and clinical aspects of hadrontherapy, a discipline that is maturing, with promising applications. We first describe the physical and biological advantages of particles and their application in cancer treatment. The contribution of the microenvironment and surrounding healthy tissues to tumor radioresistance is then discussed, in relation to imaging and accurate visualization of potentially resistant hypoxic areas using dedicated markers, to identify patients and tumors that could benefit from hadrontherapy over conventional irradiation. Finally, we consider combined treatment strategies to improve the particle therapy of radioresistant cancers.

Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer

“…Interestingly, it has been shown by the researchers involved in the Pan-Cancer Analysis Group, that despite the differences between cancers, considering initiation factors, response to the treatments and genomic alterations, there are significant similarities in the genetic and molecular pathways of different cancers that influence the outcome of treatments [31][32][33]. Given the complexity of the mechanisms responsible for maintaining the integrity of the cell, the organ and the tissue, and their response to irradiation of different qualities, a single endpoint cannot be a sufficient RS marker [12,34]. It is likely that combinations of different mechanisms, including polymorphisms in DNA gatekeeper and caretaker genes, as well as lifestyle factors are involved.…”

Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing

“…Radiation exposure is the significant modality to fight cancer, and most of patients with solid malignancies receive courses of photon or hadron therapy (reviewed in [ 1 , 2 ]). Unfortunately, antitumor radiotherapy is not always effective; in particular, the enhanced radioresistance is often exhibited by cancer cells within the hypoxic zones of tumors, and this is a great challenge [ 3 , 4 ].…”

“…Alternatively, the use of high linear energy transfer (high-LET) radiation inducing, largely, oxygen-independent cancer cell elimination would allow radiotherapists to better target hypoxic tumors. Indeed, compared with the effects of low-LET (photon) radiation, the intensity of cell death resulting from the exposure of some fractions of protons (within the Bragg peak), carbon ions or α-particles (kinds of high-LET radiation) is much less dependent on the oxygen concentration in the cell microenvironment [ 2 , 4 , 11 ]. However, the hypoxia-adapted cancer cells have a certain phenotype with specific regulation that enables them to better resist both low- and high-LET radiation ( Figure 1 ).…”

Counteracting Radio-Resistance Using the Optimization of Radiotherapy

“…In this special issue of the International Journal of Molecular Sciences, "Counteracting Radioresistance Using the Optimization of Radiotherapy", several studies have been published addressing some of the aspects related to tumor radio-resistance, with one research article [1], two communication articles [2,3], one review article [4] and one technical note [5].…”

“…In their review article, Thariat and coworkers [4] gave an up-to-date overview of the radiobiological and clinical aspects of hadrontherapy. This review articles deals with several aspects of hadronbiology and hadrontherapy in relation with treatment radio-resistance, such as proton therapy in tumor control; carbon ions and multi-ion therapy in hadron therapy; ultra-high-dose-rate flash proton therapy; hypoxia-induced radio-resistance; tumor microenvironment-induced immune tolerance; bystander effects in normal tissue tolerance in hadron therapy; biomarkers for the guidance of high-precision radiation therapy; and combined strategies to improve particle therapy.…”