Chinese Journal of Cancer Research最新文献

Hepatocellular carcinoma (HCC) is responsible for a significant number of cancer-related deaths worldwide and its incidence is increasing. Locoregional treatments, which are precision procedures guided by imaging to specifically target liver tumors, play a critical role in the management of a substantial portion of HCC cases. These therapies have become an essential element of the HCC treatment landscape, with transarterial chemoembolization (TACE) being the treatment of choice for patients with intermediate to advanced stages of the disease. Other locoregional therapies, like radiofrequency ablation, are highly effective for small, early-stage HCC. Nevertheless, the advent of targeted immunotherapy has challenged these established treatments. Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown remarkable efficacy in clinical settings. However, their specific uses and the development of resistance in subsequent treatments have led clinicians to reevaluate the future direction of HCC therapy. This review concentrates on the distinct features of both systemic and novel locoregional therapies. We investigate their effects on the tumor microenvironment at the molecular level and discuss how targeted immunotherapy can be effectively integrated with locoregional therapies. We also examine research findings from retrospective studies and randomized controlled trials on various combined treatment regimens, assessing their validity to determine the future evolution of locoregional therapies within the framework of personalized, comprehensive treatment.

Hepatocellular carcinoma (HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers; the most prominent is circulating tumor DNA (ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction (PCR) [emulsion PCR (ePCR), digital PCR (dPCR), and bead, emulsion, amplification, magnetic (BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection, treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations (either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1; 2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF; 3) DNA methylation (RASSF1A, SEPT9, KMT2C and CCNA2); 4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1; and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results. Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more diverse. Following tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal function. However, there is currently no consensus on the specific distance of distal resection margin.

Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment (TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes (TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node (SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment (systemic/radiotherapy) that may result from de-escalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging node-positive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy (SLNB), the regional nodal management of breast cancer should adhere to the concept of "updating ideas, making bold assumptions, and carefully seeking proof", make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the "net benefit" of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer (NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment (TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2 (HER2)-positive (+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.

Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.

Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.

Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

Objective: Plant-based diets have multiple health benefits for cancers; however, little is known about the association between plant-based dietary patterns and esophageal cancer (EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.

Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) of EC across 3 plant-based diet indices and further stratified the analysis by subgroups.

Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365 person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50 (95% CI, 0.32-0.77) for hPDI. In addition, the HR per 10-point increase in the hPDI score was 0.42 (95% CI, 0.27-0.66) for ECs. Conversely, uPDI was positively associated with the risk of EC, and the HR was 1.80 (95% CI, 1.16-2.82). The HR per 10-point increase in the uPDI score was 1.90 (95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.

Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

Chimeric antigen receptor-natural killer (CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice. However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.

Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.

Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with BRAF (59.7% vs. 17.3%), TERT promoter (43.9% vs. 7.4%), and TP53 mutations (11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions (15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041).

Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.