I. Nasopharyngeal carcinoma has unique clinical radiobiological behavior Like other malignant tumors, nasopharyngeal carcinoma is a clinical type that tends to local infiltration and distant metastasis, but it has unique clinical radiobiological behavior. In the 1960s, through clinical observation of nasopharyngeal carcinoma, Professor Xie Zhiguang proposed that three types of nasopharyngeal carcinoma could be distinguished in the late stage of natural progression: (1) Upstream type: with II, III, IV, V and VI cranial nerve invasion and/or skull base bone destruction, but no cervical lymph node metastasis; (2) Downstream type: with extensive unilateral or bilateral cervical lymph node metastasis involving the supraclavicular fossa The staging of nasopharyngeal carcinoma proposed by Xie did not address the factors of distant metastasis and radiosensitivity. In clinical practice, we often observe that some patients with nasopharyngeal carcinoma do not have distant hematologic metastases even though they have extensive local invasion and regional lymph node metastases, and some nasopharyngeal carcinoma has distant metastases upon diagnosis.
On the other hand, we have also observed that some patients with nasopharyngeal carcinoma have achieved long-term tumor control with only 40-50 Gy irradiation of local and regional lesions for various reasons. We analyzed nasopharyngeal carcinoma patients treated with radiotherapy alone in the 1990s, and evaluated them with no recurrence and no metastasis within 5 years. Combining the above two aspects, we propose four types of nasopharyngeal cancer radiation therapy-related typing, namely type I: radiosensitive not easy to metastasize, type II: radiation resistant not easy to metastasize, type III: radiosensitive easy to metastasize, and type IV: radiation resistant easy to metastasize. The proportion of each type is 50.6% for type I, 23.2% for type II, 20.7%h and 5.5%. Our proposed radiation therapy-related typing of nasopharyngeal carcinoma provides a basis for clinical development of individualized radiation therapy.
II. Genes involved in the regulation of radiation resistance in nasopharyngeal carcinoma On the basis of the establishment of cell models with different radiosensitivity (radiobiological properties of 14 strains (sub-strains) of human nasopharyngeal cancer cells. Cancer. 2001, 20(7):683-687), the molecular mechanism of radiation resistance in nasopharyngeal carcinoma was explored. Experimental studies have shown that inhibition of P21 function can improve the radiosensitivity of radiation-resistant nasopharyngeal carcinoma cell lines, and experimental studies have also shown that inhibition of phosphatidylinositolase family DNA-PK (including Ku70, Ku80, and DNA-PKcs) and ATM function can improve the radiosensitivity of radiation-resistant nasopharyngeal carcinoma cell lines, while clinical studies have shown that Ku70, Ku80, and DNA PKcs expression is increased in nasopharyngeal carcinoma patients with poorer prognosis. Based on cellular and animal studies and clinical studies, we propose a molecular mechanism for the involvement of the P53-P21 signaling pathway and DNA-PK/ATM genes in the regulation of radioresistance in nasopharyngeal carcinoma.