1.Research on the application of machine learning algorithms in anti-cancer drug response prediction
Yanchen TAN ; Wenwen WANG ; Jielai XIA ; Chen LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):200-208
With the continuous development of genomics and precision medicine,targeted therapy and immunotherapy targeting biomarkers have ush-ered in a new era of anti-tumor therapy.However,due to the heterogeneity of tumor cells and the variability of tumor microenvironment,there are still significant differences in response to the same drug even in patient populations with the same bio-marker enrichment.By combining omics data with drug sensitivity algorithms,the response of anti-tu-mor drugs can be predicted and transformed into personalized diagnosis and treatment strategies re-quired for precision medicine,which is expected to improve the effectiveness of anti-tumor drugs in clinical treatment.Currently,machine learning is one of the commonly used modeling algorithms for predicting the response of anti-tumor drugs.How-ever,due to differences in input data and algorithm construction methods,there is currently a lack of comprehensive literature review in this field.There-fore,this article provides a review of machine learning algorithms for predicting anti-tumor drug responses,summarizing publicly available cell ge-nome characterization datasets,machine learning algorithms,and evaluation indicators in drug re-sponse prediction,as well as the current situation and challenges faced in clinical applications,in or-der to provide methodological references for the main research problems and potential solutions of machine learning algorithms in the field of drug re-sponse prediction.
2.Research progress on targeted therapy combined with immune-acti-vating strategies in CLDN18.2-positive gastric cancer
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):146-158
Claudin 18 isoform 2(Claudin18.2,CLDN18.2)is a crucial structural protein involved in cell-cell tight junctions.While its expression is limit-ed in normal tissues,it is specifically overexpressed in malignant tumors such as gastric cancer,pancre-atic cancer,and esophageal cancer,making it a promising therapeutic target for cancer treatment.Recent advances in CLDN18.2-targeted therapies have been encouraging,and studies suggest that CLDN18.2-positive gastric cancer may possess a unique immune microenvironment.This raises the potential for combining targeted therapies with im-mune activation to achieve synergistic effects,po-tentially improving treatment outcomes for pa-tients with advanced gastric cancer.This review will focus on the immune microenvironment character-istics of CLDN18.2-positive gastric cancer and sum-marize the current research and clinical trial prog-ress in targeted therapies combined with immune activation for this specific cancer type.
3.Advances in precision diagnosis and treatment of cholangiocarcinoma
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):159-170
Cholangiocarcinoma(CCA)is a highly aggressive and heterogeneous biliary malignancy characterized by challenges in early diagnosis,limit-ed efficacy of traditional chemotherapy,and poor prognosis.Due to its significant heterogeneity at the genomic,epigenetic,and molecular levels,mo-lecular testing and targeted therapy have become increasingly important in CCA management,form-ing an integral part of the era of precision oncolo-gy.The development of next-generation sequenc-ing(NGS)has advanced research into the molecu-lar subtypes and therapeutic targets of CCA,includ-ing FGFR2 fusions/rearrangements,IDH1 muta-tions,and BRAF mutations.Recently,two phase Ⅲ clinical trials,TOPAZ-1 and KEYNOTE-966,have es-tablished the pivotal role of immunotherapy com-bined with chemotherapy in advanced CCA.While precision diagnosis and treatment in CCA have shown promising progress,this field remains in its exploratory phase and faces numerous challenges.This review summarizes recent advancements in the diagnosis,molecular targeted therapy,immuno-therapy,resistance mechanisms,and the develop-ment of novel strategies for CCA.
4.Current status and progress of targeted therapy for hepatocellular carcinoma
Zhiwen CHEN ; Longrong WANG ; Lu WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):171-182
Hepatocellular carcinoma,as a com-mon malignant tumor,remains a serious global health problem.Traditional methods such as surgi-cal resection and chemotherapy have limited ef-fects in improving the prognosis of advanced hepa-tocellular carcinoma.With the deepening of re-search into molecular mechanisms,targeted thera-py has become an important direction for the treat-ment of hepatocellular carcinoma.In this review,we summarize the main targeted drugs and associ-ated therapeutic strategies for hepatocellular carci-noma,aiming to provide references and evidence for future related research.
5.Advancements and frontiers in targeted therapy for pancreatic cancer
Nan DU ; Miaoyan WEI ; Jin XU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):183-192
The incidence of pancreatic cancer has been increasing each year,and the 5-year survival rate is still around 10%.Diagnosis and treatment strategies are major concerns in the industry.Gene sequencing and multi-omics research have revealed more signal pathways and actionable targets,offer-ing the potential for new targeted therapeutic drugs.However,current drug treatment for pancre-atic cancer still relies mainly on chemotherapy,and targeted therapy strategies are not yet fully devel-oped and require further discussion.As basic and translational research in pancreatic cancer advances and precision medicine develops,it is expected that targeted treatment for pancreatic cancer will be-come more precise and individualized in the future.This article discusses the current progress and fron-tiers of targeted treatment for pancreatic cancer.
6.Research progress on the resistance mechanism of anti-angiogenesis targeted drugs in the treatment of colorectal cancer
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):193-199
Colorectal cancer(CRC)is one of the most common malignancies worldwide,although anti-angiogenic targeted agents such as bevacizum-ab have shown significant efficacy in the treatment of metastatic CRC,however,the emergence of drug resistance is still a key obstacle affecting the suc-cess rate of treatment and survival of patients.This article reviews the progress of anti-angiogenesis targeted drugs in the treatment of CRC,the mecha-nism of drug resistance and how to solve the prob-lem of drug resistance.
7.Radix angelica sinensis and astragalus mongholicus extract mediating the Jagged1/Notch1 pathway to inhibit fibroblast transdifferentia-tion and resist radiation induced myocardial fibrosis
Wen LI ; Hugang JIANG ; Xinqiang WANG ; Yingdong LI ; Kai LIU ; Xinke ZHAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):209-215
AIM:To study the mechanism of ac-tion of radix angelica sinensis and astragalus mong-holicus extract(RAS-AM)in inhibiting fibroblast transdifferentiation(CMT)and preventing radiation-induced myocardial fibrosis(RIMF)via the Jagged1/Notch1 pathway.METHODS:Sixty male Wistar rats were randomly divided into blank group,model group,benazepril hydrochloride group,low dose RAS-AM group,medium dose RAS-AM group,and high dose RAS-AM group,with 10 rats in each group.Except for the blank group,all other groups were induced with high-energy radiation at a dose of 38 Gy to establish RIMF models.The blank group and the model group received sterile distilled water by gavage,and the other groups received medica-tion for 4 weeks of intervention:benazepril hydro-chloride group(1.0 mg·kg-1·d-1),low dose RAS-AM group(150 mg·kg-1·d-1),medium dose RAS-AM group(300 mg·kg-1·d-1),and high dose RAS-AM group(600 mg·kg-1·d-1).The general condition of rats,the ultrastructure of myocardial tissue were observed using electron microscopy,changes in myocardial tissue fibers using Masson staining,and CMT related protein Vimentin and α-SMA expres-sion using immunohistochemical staining tech-niques.ELISA was used to detect serum inflammato-ry factors IL-6 and TNF-α in rats.The levels of cTnI and ST2,and the expression of Jagged1 and Notch1 were detected by Western blot.RESULTS:Com-pared with the blank group,the model group rats exhibited symptoms such as mental fatiguem an-orexiam and loose stools;The arrangement of some myofibrils in the myocardium is disordered,with dis-solution and breakage of myofibrilsm abnormal Z-line structure in some partsm disordered mitochon-drial arrangement,rupture of mitochondrial mem-branem,and rupture or disappearance of mitochon-drial ridge structure in some parts.A large amount of collagen fibers proliferate and deposit in the myo-cardium,and the fibrotic area significantly increases(P<0.01);The expression of myocardial tissue Vi-mentin α-SMA protein increased(P<0.05),while the expression of Jagged1 and Notch1 proteins de-creased(P<0.05);serum IL-6 and TNF-α,the expres-sion of inflammatory factors such as cTnI and ST2 in-creased(P<0.05).compared with the model group,the RAS-AM and benazepril hydrochloride groups showed varying degrees of improvement in general conditions;the pathological changes of myocardial ultrastructure have been improved,and myocardial fibrosis has been alleviated;The area of collagen fi-bers significantly decreased(P<0.01);Myocardial tis-sue Vimentin α-SMA protein expression decreased(P<0.05),while Jagged1 and Notch1 expression in-creased(P<0.05);Serum IL-6 and TNF-α,The expres-sion of inflammatory factors such as cTnI and ST2 decreased(P<0.05).CONCLUSION:RAS-AM may al-leviate RIMF by intervening in the Jagged1/Notch1 pathway to inhibit CMT.The specific mechanism still needs further investigation
8.Ameliorating effect of total flavonoids of rhododendron on brain oxi-dative stress injury in cerebral ischemia-reperfusion rats
Xiaohai YU ; Yu JIN ; Minqiong SUN ; Hui CONG ; Qianying GUO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):216-221
AIM:To explore the protective effect of total flavonoids from rhododendron(TFR)on oxi-dative stress injury in the brain of rats subjected to cerebral ischemia/reperfusion(I/R).METHODS:For-ty male SD rats were randomly divided into 5 groups:sham operation group(Sham group),cere-bral ischemia-reperfusion group(MCAO group),and Cerebral Ischemia/Reperfusion with TFR treat-ment groups(TFR 50,100,200 mg/kg groups).The MCAO group and TFR-treated groups underwent ischemia/reperfusion surgery,and the TFR-treated groups received TFR intragastrically for 14 consecu-tive days following the ischemia/reperfusion injury.After 14 days,comparisons were made in terms of neurological function scores,serum inflammatory factors,oxidative stress indicators,and brain injury markers.Additionally,histological examination of brain tissue morphology using Hematoxylin and Eo-sin(HE)staining,observation of cerebral blood flow through cerebral blood flow imaging,and measurement of lactate dehydrogenase(LDH),neu-ron-specific enolase(NSE)activity in serum,inter-leukin-1(IL-1),interleukin-6(IL-6)levels,superox-ide dismutase(SOD)activity,malondialdehyde(MDA)content,nitric oxide(NO)content,and nitric oxide synthase(NOS)activity were performed.RE-SULTS:Compared to the Sham group,MCAO rats exhibited abnormal neurological function scores,severe damage to the microstructure of brain tis-sue,noticeable changes in brain morphology,ele-vated activities of LDH and NSE,increased levels of IL-1 and IL-6,elevated MDA content,and de-creased SOD,NOS activity,and NO content.In com-parison to the MCAO group,rats treated with TFR at doses of 50,100,and 200 mg/kg showed recov-ery of abnormal neurological function scores,re-duced damage to the microstructure of brain tis-sue,decreased activities of LDH and NSE,lowered levels of IL-1 and IL-6,reduced MDA content,and increased SOD,NOS activity,and NO content.CON-CLUSION:Total flavonoids from Rhododendron can protect against cerebral ischemia/reperfusion inju-ry,reducing oxidative stress levels.
9.Evidence map on the treatment of heart failure with Yiqifumai injec-tion
Shichao LYU ; Yunjiao WANG ; Yiming ZUO ; Hongcai SHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):222-231
AIM:To display the distribution of evi-dence in the field of Yiqifumai injection treatment for heart failure.METHODS:To retrieve relevant da-tabases such as CBM,CNKI,Wanfang,VIP,Co-chrane Library,PubMed,Embase,and Web of Sci-ence,and search for the China Clinical Trial Regis-try,ClinicalTrials.gov and collect clinical studies,sys-tematic evaluations,and guideline studies on the treatment of heart failure with Yiqifumai injection.The evidence map research method use a table to display the proportion of literature,sample size,co-morbidities,and quality evaluations of systematic evaluations.Use a pie chart to display the propor-tion distribution of research types,a line chart to describe publication trends,and a bubble chart to display the distribution of evidence.RESULTS:The overall number of articles on the treatment of heart failure with Yiqifumai injection is in a steady development stage.Clinical studies are mainly small sample,single center,short-term randomized controlled trials,with a sample size of 60-100 cases and an intervention duration of mostly 14 days.The underlying disease is mainly coronary heart dis-ease.Clinical research evidence tends to support the therapeutic effect of Yiqifumai injection com-bined with conventional Western medicine in im-proving heart failure patients'heart function and quality of life.However,there are also issues such as low overall quality of research,unreasonable clinical trial design,small sample size,incomplete selection of outcome indicators,low international recognition of certain outcome indicators,and lack of reporting on long-term outcomes The overall quality of randomized controlled trials andsystem-atic evaluation methodology is low.CONCLUSION:In the future,more large sample,multicenter clini-cal randomized controlled trials should be conduct-ed to obtain higher-level evidence-based medicine evidence to fully demonstrate the advantages of traditional Chinese medicine treatment,and pro-mote the common development of traditional Chi-nese medicine cardiology and evidence-based med-icine.
10.Analysis of risk factors for intolerance of valsartan with Sakubatrol in patients with heart failure
Jia WANG ; Lei WANG ; Binfa XU ; Feng LIU ; Xin WEN ; Min CHEN ; Yinsi GAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):232-237
AIM:To investigate the risk factors for intolerance to sacubitril/valsartan in the treatment of heart failure.METHODS:A total of 124 heart fail-ure patients hospitalized in our hospital from May 2023 to May 2024 were collected.Logistic regres-sion analysis and nomogram analysis were used to identify the risk factors for drug tolerance.RE-SULTS:22 patients exhibited intolerance,with low blood pressure being the primary cause(P<0.05).Multivariate regression analysis found that patients with a low BMI(OR 95%CI 1.814(1.385-2.525))and those without concomitant right heart failure(OR 95%CI 4.998(1.552-17.301))were more likely to ex-perience drug intolerance.The model had a stable C-index of 0.923(95%CI=0.863-0.975).CONCLU-SION:Low BMI and absence of right heart failure are risk factors affecting the tolerance to sacubitril/valsartan,which has certain value for guiding clini-cal treatment.Large-sample clinical studies are still needed to confirm these findings.

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