中华肿瘤杂志最新文献

Over the past half-century of the global effort against cancer, the vast majority of investigations in both tumor basic research and clinical practice have centered on the "somatic mutation" theory, such as in molecular classification, individualized precision medicine strategies, gene therapy approaches, the development of neoantigen-based tumor vaccines, and advancements in sequencing technologies. Even in the extensively studied tumor microenvironment (including tumor immunity), which has garnered significant attention in recent years, the underlying mechanisms frequently revert to specific genes and mutations within tumor cells or microenvironmental cells as the primary driving forces. However, despite the dominance of the "somatic mutation" paradigm, truly effective approaches for curing cancer in clinical settings remain elusive. Undoubtedly, if the prevailing "somatic mutation theory" continues to monopolize cancer research, meaningful progress in understanding and treating cancer will likely remain frustratingly out of reach. At this critical juncture in the evolution of cancer research, a comprehensive re-evaluation of cancer not only is necessary but also imperative, highlighting the urgent need for a profound transformation in our conceptual framework. This article systematically elucidates the novel perspective offered by the "tumor system" for comprehending the essence of cancer, the foundational principles of "tumor ecology" and their potential applications in treatment, and explores in depth the theoretical framework and research significance of the emerging field of "ecological pathology". Beyond merely advocating for the abandonment of the currently dominant linear reductionist paradigm of cancer, this commentary strives to construct a pragmatic and systematically structured framework to guide the trajectory of the "post-genomic revolution in oncology" and the "tumor ecological philosophy", ultimately fostering the realization of the overarching societal goal of eradicating cancer.

Tumour neoantigen sprimarily refer to a specific group of tumour antigens derived from tumour mutant proteins, but also including antigens generated by the oncogenic viruses integrated into the genome, which are not expressed by normal cells in the human body but are specifically expressed in tumor cells, and are capable of triggering the tumour-specific cellular and humoral immunity in the host. In recent years, significant advances in tumor immunotherapy such as therapeutic oncology vaccines, and adoptive cell therapy (ACT) have been acquired. However, standalone tumor therapeutic vaccines exhibit several drawbacks. They possess low immunogenicity, face a substantial tumor burden, and are highly susceptible to the immunosuppressive microenvironment. Consequently, when applied in isolation during clinical practice, their therapeutic efficacy remains limited. Compared with immunotherapies such as immune checkpoint inhibitors and tumor vaccines, ACT is less affected by the immunosuppressive microenvironment in the body and can generate a sufficient number of killer cells. The crux of ACT lies in the generation of immunogenic tumor-specific killer cells. Neoantigens enhance the immunogenicity and anti-tumor specificity of ACT. Among them, the ACT targeting mutant gene mutations, including ERBB2IP, KRAS and TP53, as well as those derived from viruses such as Epstein-Barr virus (EBV) and human papillomavirus (HPV), is primarily summarized. Moreover, the existing issues of neoantigen-specific ACT and corresponding countermeasures are summarized and discussed.

Objective: To understand the burden of cancer disease in Hebei Province in recent years and to analyze the change trend of cancer in Hebei Province from 2011 to 2020. Methods: The incidence and death data of cancer were collected from 38 cancer registries in Hebei Province during 2011-2020. The incidence (mortality) rate, standardized incidence (mortality) rate and composition ratio of each region, sex, and age were calculated respectively, and the incidence and death of major cancers in our province were summarized. The age-standardized morbidity (mortality) rates of China and the world population were calculated using the 2000 China standard population composition and Segi's world population composition respectively. Trend analysis of morbidity and mortality was performed and average annual percentage change (AAPC) was calculated. Results: In 2020, the crude cancer incidence rate and the age-standardized morbidity rate of China was 229.36/100 000 and 147.06/100 000, respectively. An estimated 171 600 new cases were reported in the province. The crude cancer mortality rate and the age-standardized mortality rates of China was 146.38/100 000 and 85.33/100 000. The estimated number of deaths in the province is 108 900. In the cancer registration areas of Hebei Province, 84% of all cancer patients occurred in people 50 years of age and older. From 2011 to 2020, the incidence and mortality of cancer in Hebei Province showed a decreasing trend. The AAPC was -4.2% (P＜0.001), which decreased from 206.61/100 000 in 2011 to 143.74/100 000 in 2020. The world standard mortality rate of cancer was 147.69/100 000 in 2011, and decreased to 84.79/100 000 in 2020. The AAPC was -5.7% (P＜0.001). The world-standard incidence and mortality of lung cancer, esophageal cancer, gastric cancer, liver cancer and colorectal cancer decreased from 2011 to 2020. The AAPCs of the world-standard incidence were -4.0%, -12.3%, -9.4%, -6.0% and -1.6%, respectively. The AAPCs of the world-standard mortality were -4.9%, -11.3%, -8.5%, -5.7% and -3.3%, which were statistically significant. The incidence of thyroid cancer increased rapidly, the AAPC of which was 9.7% (P＜0.001). The rates of female breast cancer and male prostate cancer in Hebei Province were stable. Conclusions: The world-standard incidence and mortality of cancer in Hebei Provincial cancer registries areas show a downward trend from 2011 to 2020. However, the cancer incidence and mortality in Hebei Province are still at high levels. It's necessary to strengthen cancer prevention and control in Hebei Province, improve the awareness of cancer prevention and control in the whole society, and promote the concept of tertiary cancer prevention to reduce the cancer burden in Hebei Province.

Objective: To study the clinical and pathological features, immunophenotypes, molecular genetics characteristics, differential diagnosis, and prognostic factors of pulmonary and tracheal glomus tumors. Method: Eight cases of pulmonary and tracheal glomus tumors were collected in Jiangsu Provincial Hospital (including 1 consultation, from Gaochun People's Hospital, Nanjing, China) between May 2015 and April 2023, and their clinical and imaging data, pathological morphology, and immunohistochemical characteristics were retrospectively analyzed. Gene testing and follow-up were performed. Result: There were 5 males and 3 females with onset ages ranging from 29 to 75 years old, median age 63.5 years. Among the patients, 5 cases were located in the trachea and 3 cases in the lungs. Under light microscopy, 5 cases were benign glomus tumors with clear boundaries, diffuse sheet or nest-like distribution, small, round or short spindle-shaped tumor cells, rounded and centered nuclei, and no obvious nuclear mitosis was seen. Two cases of glomus tumor of uncertain malignant potential showed an infiltrative growth pattern involving smooth muscle, nerves and blood vessels with necrosis and calcification, the tumor cells were more uniform in size, round or short spindle-shaped nuclei, and no obvious nuclear mitosis was seen; One case of malignant glomus tumor was seen in sarcomatous areas, lung membrane invasion and necrosis, the tumor cells were highly heterogeneous, binucleated and multinucleated, with nuclear mitoses of 20/50 high power field (HPF), and pathologic nuclear mitoses were easy to be seen. Immunohistochemically, SMA, Calponin, H-caldesmon, Vimentin and Collagen Ⅳ were all positive (8/8). Some cases expressed Syn (3/8) and Bcl-2 (4/8). The Ki-67 proliferation index was 1-2% (7/8) and 40% (1/8). BRAF V600E were detected as wild-type (8/8), and no mutations were detected in exons 2, 3, and 4 of KRAS human EML4-ALK fusion gene were negative in 5 surgical cases. Case 6 showed HMBOX1-ALK gene fusion, TERT gene mutation and CDKN2A gene deletion, and case 8 showed CARMN-NOTCH2 gene fusion. Seven cases were followed up (8-103 months, median follow-up time 30 months), 1 case was lost, 1 case recurred 21 months after surgery, and others with no evidence of recurrence or metastasis. Conclusions: Pulmonary and tracheal glomus tumors are very rare and need to be differentiated from other common tumors by combining pathological morphology and immunohistochemistry. Maybe there are some differences in the malignant diagnostic criteria and molecular genetic characteristics between visceral derived glomus tumors and soft tissue derived tumors of the same kind, such as limbs and skin. More data accumulation is needed.

Background: To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex^® in Chinese patients with premenopausal breast cancer. Methods: From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex^® every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results: A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex^®. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex^®. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex^® group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion: LY01005 is as effective as Zoladex^® in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective: To investigate the uptake patterns of 18F-fluorodeoxy glucose (¹⁸F-FDG) in the endometrium using positron emission tomography (PET) imaging and to differentiate these from stage IA endometrial cancer. Methods: From September 2022 to April 2024, a prospective inclusion of 354 women without gynecological diseases and no hormone usage who underwent ¹⁸F-FDG PET-CT examinations at the affiliated hospital of Qingdao University were set as the physiological group, while a group containing 42 cases of Stage IA endometrial carcinoma was also set. The physiological group was divided into five groups based on the menstrual cycle: menstrual period, proliferative phase, ovulatory phase, secretory phase, and menopausal phase. The images were analyzed using visual and quantitative measurements; quantitative analysis indicators were standardized uptake value maximum (SUVmax) and the region of interest/liver ratio (R/L value). Receiver operating characteristic (ROCs) curve was used to determine the optimal cutoff values for SUVmax and R/L value. A clinical model was established using binary logistic regression, and ROC curves were drawn to evaluate the predictive performance of the model. Results: The uptake of ¹⁸F-FDG in the endometrium exhibited cyclical variations throughout different physiological phases, with higher uptakes observed during the menstrual and ovulation phases (SUVmax values of 6.66±3.26 and 3.89±1.21, respectively), which are significantly higher than those in the proliferative phase [median SUVmax of 2.54 (2.02, 3.47)], secretory phase (SUVmax of 2.55±0.86), and menopausal phase [SUVmax median of 2.04 (1.69, 2.29)]. During the menstrual and ovulation phases, the radiotracer accumulation patterns were triangular in 105 cases, oval in 32 cases, and round-like in 2 cases. All 42 cases of endometrial cancer showed ¹⁸F-FDG uptake, with radiotracer accumulation patterns being round-like in 17 cases, oval in 10 cases, triangular in 9 cases, and irregular in 6 cases. There were statistically significant differences in the shapes of radiotracer concentration between the menstrual, ovulatory periods, and endometrial carcinoma (both P＜0.001). The SUVmax and R/L values in menstrual period and ovulatory period were significantly lower than that in endometrial carcinoma group (P＜0.001). During the menstrual phase, the optimal cutoff values for SUVmax and R/L in distinguishing between endometrial and endometrial cancer were 12.59 and 3.81, respectively, with corresponding AUCs of 0.885 and 0.842. After incorporating endometrial uptake morphology into the model, the AUCs was improved to 0.969 and 0.948, respectively. During the ovulatory phase, the optimal cutoff values for SUVmax and R/L were 5.96 and 2.85, respectively, with AUCs of 0.984 and 0.968. After integrating endometrial uptake morphology into the model, the AUCs were increased to 0.999 and 0.998, respec

Objective: To analyze the incidence, mortality, survival patterns, and distribution characteristics of modifiable risk factors for colorectal cancer in selected global regions. Methods: Secondary analysis was conducted using data from the GLOBOCAN database and previous literature. We described the number of cases and age-standardized rates (ASRs) of incidence and mortality for colorectal cancer in China, the United States, the United Kingdom, and globally in 2022 and 2020, with gender-stratified analysis. ASRs were calculated using Segi's world standard population. Temporal trends in 5-year net survival rates were compared across three periods (2000-2004, 2005-2009, 2010-2014) among countries. Regional distribution differences in colorectal cancer deaths attributable to modifiable risk factors by gender were assessed in China. Results: In 2022, global colorectal cancer incidence and mortality were estimated at 1.926 million new cases and 904 000 deaths. China accounted for 27% of both global incidence (517 000 cases) and mortality (240 000 deaths). China's age-standardized incidence rate (20.1 per 100 000) was lower than those of the United States (27.0 per 100 000) and the UK (30.9 per 100 000). However, China's mortality rate (8.6 per 100 000) exceeded that of the US (7.9 per 100 000) but was lower than the UK (11.8 per 100 000). Compared to 2020, China demonstrated significant mortality reductions in 2022: males declined from 14.8 to 10.9 per 100 000, females from 9.4 to 6.5 per 100 000. Five-year net survival rates in China improved across periods for colon cancer (51.4%, 55.6%, 57.6%) and rectal cancer (49.5%, 52.5%, 56.9%), yet remained consistently lower than US and UK rates. Modifiable risk factors contributed to 45.1% of male and 41.4% of female colorectal cancer deaths in China, with marked regional disparities. Conclusions: China exhibits higher colorectal cancer incidence and mortality than global averages, with survival gaps persisting compared to developed nations. Regionally tailored comprehensive prevention strategies are essential to reduce disease burden through risk factor modification and optimized clinical management.

Objective: To investigate whether F.nucleatum affects the chemotherapy resistance of colorectal cancer by regulating ABC subfamily G subtype 2 (ABCG2), in view of the fact that the correlation between the two has not been reported. Methods: Oxaliplatin was used to interfere with colorectal cancer cells and co-cultured with F.nucleatum to establish a chemotherapy-induced model of microbial infection. Calcein AM/PI cell staining, trypan blue staining, and cell counting kit 8 (CCK-8) method were used to detect cell activity. Real-time fluorescence quantitative polymerase chain reaction and western blot were used to detect ABCG2 mRNA and protein expression levels in colorectal cancer cells. The target gene was knocked down by constructing shRNA plasmids. The HCT-116 cell F.nucleatum infection model was constructed and transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses were performed to determine the differential gene expression enrichment pathways. Genistein (GST) was used as an E-cadherin blocker, and triclabendazole sulfoxide (TCBZSO) was used as an ABCG2 blocker. Immunofluorescence was used to detect E-cadherin and β-catenin protein expressions and intracellular localization levels. The subcutaneous xenograft model of nude mice was constructed in vivo, and the expression level of ABCG2 protein in tissues was detected by immunohistochemical staining. Results: CCK-8 results showed that F. nucleatum+oxaliplatin group [HT-29, (92.26±1.66)%; HCT-116, (82.13±1.84)%] cell relative survival rate was higher than that of oxaliplatin group [HT-29, (79.64±3.72)%; HCT-116, (67.56±2.96)%; P＜0.001]. The relative survival rate of oxaliplatin and F. nucleatum co-culture group with ABCG2-knockdown HCT-116 cells [(61.44±1.48)%] was lower than that of F. nucleatum and oxaliplatin co-cultured with HCT-116 cells [(69.29±4.45)%, P=0.015]. GO enrichment analysis showed that HCT-116 cells co-cultured with F.nucleatum were significantly enriched in "β-catenin binding", "cadherin binding" and "regulation of Wnt signaling pathway". RT-qPCR results showed that the relative expression of ABCG2 mRNA in F.nucleatum + genistein group was significantly lower than that in F.nucleatum group (P＜0.001). The results in vivo showed that the tumor weight in the F.n+L-OHP+TCBZSO group [(0.12±0.02)g] was lower than that in the F.n+L-OHP group [(0.33±0.05)g, P＜0.001]. Immunohistochemistry suggested that the promotion of ABCG2 protein expression by F. nucleatum was blocked after TCBZSO intervention. Conclusion: F. nucleatum up-regulates ABCG2 expression through E-cadherin/β-catenin signaling pathway to promote colorectal cancer resistance to oxaliplatin.

Objective: To analyze the epidemiological characteristics and survival rate of nasopharynx cancer (NPC) in Guangdong Province from 2011 to 2019. Methods: Based on the cancer registry data of Guangdong Province from 2011 to 2019, the crude rate, age-standardized rate (the standard population was the fifth Chinese national census of 2000) and age-specific rate of incidence and mortality of NPC were calculated, and the regional distribution characteristics were also explored. The average annual percentage change (AAPC) of the incidence and mortality rates were analyzed by using Joinpoint regression model. The observed survival rate was estimated by period survival method, and the expected survival rate was calculated by Ederer Ⅱ method. Results: The crude incidence rate and age standardized incidence rate of NPC showed a decreasing trend, and the AAPC was -1.9% and -2.1%, respectively (P＜0.05). The crude mortality rate and age standardized mortality rate of NPC also showed a decreasing trend, and the AAPC was -4.8% and -4.6%, respectively (P＜0.05). The incidence and mortality rates are both higher in men than those in women during the nine years. The age-specific incidence rate of NPC reached its peak in the 50-64 years old age group, and the mortality rate reached its peak in the 65-74 years old age group in Guangdong province. In 2019, the age-standardized incidence rate of NPC was 9.49/100 000 (13.89/100 000 in men and 5.19/100 000 in women). The incidence and mortality of NPC varied greatly among different areas, and the areas with highest incidence and mortality rate were both in Zhaoqing. In 2020, the five-year observed survival rate of NPC in Guangdong Province was 67.2%, the 5-year relative survival rate was 75.3% and the 5-year standardized relative survival rate was 68.9%. Conclusions: Both the incidence and mortality rates of NPC in Guangdong province show decreasing trend, and the decreasing level of the mortality rate is higher than that of the incidence rate, but the two rates are still at high levels. The prevention and control work should focus on male, middle-aged and elderly population and Zhaoqing, Zhongshan, Foshan areas.

Anaplastic lymphoma kinase (ALK) fusion represents one of pivotal driver genes within the realm of non-small cell lung cancer (NSCLC). ALK-tyrosine kinase inhibitors (ALK-TKIs) have demonstrated remarkable therapeutic efficacy for patients afflicted with ALK-positive NSCLC. As of December 31, 2024, eight ALK-TKIs, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, iruplinalkib, and invonalkib have garnered approval from the China National Medical Products Administration (NMPA) (Ranking according to the approval time for marketing by NMPA), providing targeted treatment agents for ALK-positive NSCLC patients. To standardize the application of ALK-TKIs, The Chinese Association for Clinical Oncologists and the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care has organized experts to compile the "Clinical practice guideline on anaplastic lymphoma kinase-tyrosine kinase inhibitors for non-small cell lung cancer (2025 edition)". This guideline provides recommendations in four aspects, encompassing ALK fusion testing, ALK-TKI targeted therapy, ALK-TKI adverse events management, and patient post-treatment follow-up, thus serving as a valuable reference for the standardized treatment of Chinese ALK fusion-positive NSCLC.