The morbidity and mortality of gallbladder cancer were rising. At present, there was no effective chemotherapy regimen, so it was of great practical significance to explore new therapy target. Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation and metabolic constraints. In recent years, it had become a research hotspot. Many studies had been carried out on the relevant biological mechanisms such as liver cancer, breast cancer, pancreatic cancer, and other cancer. At present, there are still few studies on ferroptosis in gallbladder cancer, and its relevant mechanisms need further in-depth analysis, which opens up a new research direction for exploring the treatment of gallbladder cancer.
ObjectiveTo understand the latest progress of transcatheter arterial chemoembolization (TACE)-based combination therapies for unresectable liver metastasis from colorectal carcinoma, and to explore the safe and effective combination therapies in order to controlling the rapid progress of disease and improving the quality of life of patients.
MethodsThe literatures about TACE-based combination therapies of liver metastasis from colorectal carcinoma and the latest advance in researches of this field at home and abroad were collected, and the application of combination therapies, the advantages and features of the combined treatments were reviewed.
ResultsTACE was a safe and effective therapeutic modality in treating primary liver cancer or secondary liver cancer.Compared with a single treatment, TACE-based combination therapies had distinct advantages to patients with liver metastasis from colorectal carcinoma not only improved the quality of life but also prolonged the survival time.With the emerging of various kinds of new drugs and the rapid development of a variety of interventional treatments, it could bring long-term survival benifit for patients with liver metastasis from colorectal carcinoma.
ConclusionsDoctors should pay attention to the combined treatments of patients with liver metastasis from colorectal carcinoma, improve the knowledge of personalized medication about advanced tumors and actively promote more usage of combination therapies.
ObjectiveTo systematically elucidate the resistance mechanism of targeted drug therapy for breast cancer and to discuss future direction of optimized treatment strategies. MethodA literature review on targeted therapy for breast cancer had been conducted based on recent domestic and international research. ResultsContemporary breast cancer targeted therapies mainly comprised human epidermal growth factor receptor 2 (HER2)-directed agents, CDK4/6 inhibitors, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway blockers, poly (ADP-ribose) polymerase inhibitors, and immune checkpoint modulators, etc. While these agents had conferred subtype-specific survival benefits, resistance developed through target mutations, compensatory signaling, epigenetic alterations, drug efflux pumps, among other mechanisms. Emerging strategies for reversing drug resistance included dual-targeted approaches (such as trastuzumab in combination with pertuzumab), dynamic monitoring of drug-resistant gene mutations by liquid biopsy, epigenetic modulators, etc. ConclusionsDrug resistance remains a key bottleneck limiting long-term efficacy of breast cancer targeted therapy. Future research should integrate multi-omics approaches to decipher tumor heterogeneity, implement combinatorial multi-target inhibition with real-time monitoring of multidimensional interventions, and leverage artificial intelligence to predict resistance evolution. This integrated strategy is expected to enable personalized combination therapies, ultimately overcoming drug resistance and improving patient survival outcomes.
ObjectiveTo review the recent progress of the molecular targeted therapy for thyroid cancer.
MethodsThe literatures of molecular etiology for thyroid cancer, mechanism and evaluation of targeted therapy via Medline and CHKD database were reviewed.
ResultsSo far, four molecular targeted drugs (Sorafenib, Lenvatinib, Vandetanib, and Cabozantinib) have been approved for treatment of advanced thyroid cancer by FDA. They can mainly improve the patient's progression-free survival. Besides, several new molecular targeted drugs have accomplishedⅠphase or Ⅱ phase clinical trials. These drugs may be new options for treatment of advanced thyroid cancer in the future.
ConclusionsMolecular targeted drugs have been the main therapeutic method for advanced thyroid cancer. However, we should invent more effective new drugs and investigate the drug combination to improve the therapeutic effect.
ObjectiveTo summarize the latest research of long non-coding RNA (lncRNA) as competitive endogenous RNA (ceRNA) and its targeting technology in pancreatic cancer, so as to provide new ideas for lncRNA targeted intervention or as an early diagnostic marker of pancreatic cancer. MethodThe domestic and foreign literature on researches of lncRNA as ceRNA and its targeting technology in the pancreatic cancer was searched and reviewed. ResultsAt present, the growing number of evidences showed that in pathological states such as tumors, the abundance of intracellular lncRNAs was sufficient to trigger ceRNA crosstalk. The lncRNA played a role like “sponge” through the complementary binding of incomplete base of miRNA with miRNA response elements, then adsorbed miRNA, and thus changed the activity and effectiveness of miRNA. It also regulated the expression of downstream target genes. Moreover, a large number of studies had identified that the lncRNA-mediated ceRNA regulatory network, namely lncRNA/miRNA/mRNA axis, played a role in promoting or inhibiting the occurrence and progression of pancreatic cancer through a variety of cellular functions. In addition, many technologies targeting lncRNA, such as small interfering RNA, antisense oligonucleotides, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9, and small molecule inhibitors, etc. had been widely studied and acquired important results in preclinical research. ConclusionsThe ceRNA hypothesis is a functional complex composed by non-coding RNAs and mRNAs with non-coding properties, forming a ceRNA network of multi-level and cross-regulatory on the transcriptome. Epigenetic modification and key post-transcriptional regulation of lncRNA have been achieved through ceRNA network mechanism, which has become a successful paradigm for exploring the function of lncRNA. The tumor suppressive and promoting effects and mechanisms of many lncRNAs in the occurrence and development of pancreatic cancer are explored in many studies. Moreover, the continuous progress of targeted lncRNA technology provides conditions for study of lncRNA. LncRNA has a potential to be used as a biomarker for precancerous diagnosis and prognosis of pancreatic cancer.
ObjectiveThis review has summarized in detail the advances in computed tomography (CT) and magnetic resonance imaging (MRI) imaging in evaluating the efficacy of targeted therapy for gastrointestinal stromal tumor (GIST).MethodsTo summarize the image-related guidelines, consensus, international conference reports, and relevant knowledge of clinical research on the evaluation of the efficacy of GIST targeted therapy in recent years.ResultsThe CT and MRI manifestation after targeted treatment of GIST was closely related to pathological changes, including necrosis, cystic degeneration, and bleeding. CT was the preferred imaging method. Functional magnetic resonance imaging, such as diffusion weighted imaging (DWI), had made some progress. The main criteria for evaluating the efficacy of GIST targeted therapy were RECIST 1.1 and Choi criteria.ConclusionCT and MRI play an important role in evaluating the efficacy of targeted therapy for GIST.
ObjectiveThis study is aimed to determine the expression of ubiquitin-specific peptidase 39 (USP39) protein in the colorectal cancer (CRC) tissues, and the effect of silencing USP39 gene on the cell growth and cell cycle distribution of CRC cells.Methods① The expressions of USP39 protein in CRC tissues and its paracancerous tissues were determined by immunohistochemical staining method. ② By lentiviral infection, Lv-shUSP39 (KD-1 and KD-2 group) and Lv-shCon (shCon group) were transferred into SW1116 and HCT116 cells, and cells of blank control group did not received any treatment (Con group). To determine the role of USP39 gene in cell growth, MTT assay was performed to draw growth curve, and cell cycle distribution of CRC cells in the 4 groups were determined by flow cytometer.Results① The expression of USP39 protein was higher in CRC tissues compared to adjacent tissues (P=0.007). ② For SW1116 and HCT116 cells, the cell proliferation ability of KD-1 and KD-2 groups were remarkably decreased than those in corresponding shCon and Con groups on 3, 4, and 5-day (P<0.05). ③ Flow cytometry assay showed that, the percentage of G0/G1 phase cells were decreased obviously (P<0.05), while increased significantly in percentage of G2/M phase and number of sub-G1 phase cells in KD-1 group compared with that in the Con group and shCon group of SW1116 and HCT116 cells (P<0.05).ConclusionsThe expression of USP39 protein is highly expressed in CRC tissues. Knockdowning of USP39 gene can inhibit cell proliferation and promote cell apoptosis.
HtrA serine peptidase 2 (HTRA2) is a serine protease existing in the mitochondrial gap. Among the four members of the human HtrA serine peptidase family, HTRA2 is the only protease with clear localization in the cell. It plays a dual role in the maintenance of mitochondrial homeostasis and the promotion of cell apoptosis. HTRA2 has been found to be associated with a variety of tumors. Meanwhile, the expression of HTRA2 can enhance the sensitivity of chemotherapy and radiotherapy, and can be used as a diagnostic and prognostic marker for malignant tumors and a target for combined therapy. This article reviews the structure, biological function and role of HTRA2 in malignant tumors, in order to provide clues and basis for early diagnosis and individualized treatment of tumor patients.
The mechanisms behind diabetic retinopathy (DR) can be ascribed primarily to retinal microvascular abnormalities, excessive inflammatory response and neurodegeneration. Circular RNA (circRNA) is a type of endogenous non-coding RNA with a special circular structure, which is mainly composed of precursor RNA after shearing and processing. It is widely present in the retina and participates in the occurrence and development of various fundus diseases. CircRNAs express in an abnormal way in retina, serving as “the sponge” for miRNA so as to play roles in dysfunction of retinal vascular, inflammatory response and neurodegeneration in the development of DR. Further studies for circRNAs in DR will illustrate pathophysiology of DR more deeply, shedding light on circRNAs becoming novel biomarkers and molecular targets for diagnosis and treatment, thus achieving the goal of early diagnosis and precise therapy of DR.
Objective To summarize the research progress of copper and its derivatives in gastrointestinal tumors in recent years, aiming to provide reference for clinical diagnosis and treatment decisions. Method The literatures related to copper homeostasis and copper death in recent years were read and summarized, and the research progress on the role of copper in cancer and copper applications in cancer diagnosis and treatment was reviewed. Results Copper was an essential trace element involved in a variety of basic biological processes. Elevated levels of copper in serum and tissues were associated with the development of tumors. As the mechanisms of copper action in various gastrointestinal tumors were being investigated, the use of copper and related derivatives in the treatment of cancer patients had become a new strategy. Conclusion Copper and its derivatives have a promising future in the treatment of gastrointestinal tumors, but their benefits in clinical patients still need to be demonstrated in numerous clinical trials.
