In spite of the important progresses on cacer research, malignant tumors are still one of the principal causes of death all over the world. For example, with an incidence between 33.9 and 60.0 cases per 100,000 people per annum, malignan lung tumours belong to group of the most common cancers worldwide.
Radiotherapy (RT) remains an effective conventional method of treatment for patients with cancer. Approximately 50% of patients with cancer are estimated to receive RT as part of their treatment, and it has been reported that 40% of patients are cured by the therapy. However, the clinical efficacy of radiotherapy is compromised by the development of radioresistance of the tumor cells during the treatment.
The objective of RT is to destroy or slow tumor growth by using high-energy radiation, such as X-rays, gamma rays, electrons, protons, neutrons, and carbon ions. RT efficacy is influenced by the type of radiation, the total dose, the fractionation rate and the targeted organs. In general different tumors show different sensitivity to RT. The primary intracellular target of RT is DNA. RT triggers DNA damage through the direct deposition of
ionizing energy into the DNA or via the production of free radicals. The DNA damage could be efficiently detected and repaired, conversely inefficient mechanisms of DNA repair induce different cell death.
RT efficacy in mainly impeded by the molecular mechanisms of radioresistance mediated by tumor cells. In order to evade cell death, tumor cells have developed a variety of strategies, including enhancing DNA repair, activating cell-cycle checkpoints, regulating the self-renewal and differentiation of cancer stem cells, enhancing cellular metabolism, regulating the activities of autophagy, and regulating the expression of non-coding RNA. The importance of understanding these mechanisms is especially related to the use of unconventional fractionated RT, such ad SBRT or FLASH RT [1].
Furthermore, it is well known that the primary cause of failure in convetional cancer therapy is tumor metastatasis. Some responses in healthy tissues exposed to RT seem to enhance hospitable environment for metastatic growth. On the other hand RT can also initiate anti-tumor immune responses.
This is in addition to its direct killing potential of the tumor cells by damaging their DNA with high-energy rays. It is evident the necessity to study the molecular regulatory mechanisms between RT and the host’s immune responses. This allows a combination of different treatments and improvement of the efficacy of RT. A combination of immunotherapy and RT has risen to the forefront of cancer research studies [1]. When combined with immunotherapy, the primary consideration for irradiation dose is to maximize synergy with immunotherapy rather than maximize DNA damage on the tumor cells. However, more studies are needed to explore better immunotherapy regimens for the different type and stages of cancer.
In the future [1] the synergy of RT with immunotherapy must be deepened and more precise image-guided techniques are needed to maximize the killing effect and minimize off-tumor cytotoxicity. In general these recent studies focus on novel radiosensitizing drugs and new combination therapies for cancer.
[1] Deciphering the Biological Effects of Radiotherapy in Cancer Cells. Lu, Z.; Zheng, X.; Ding, C.; Zou, Z.; Liang, Y.; Zhou, Y.; Li, X; Biomolecules 2022, 12, 1167.
