Peptide drugs: a new direction in cancer immunotherapy

Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.

Research Progress on the Bone Metastasis Mechanism of Prostate Cancer and Bone-Targeted Drugs

Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involving multiple factors and steps.In recent years,with in-depth research on the mechanism of prostate cancer bone metastasis and the development of new drugs,important progress has been made in the treatment of prostate cancer bone metastasis.Based on this,this article introduces the mechanism of prostate cancer bone metastasis and the research progress of several bone-targeted drugs to provide reference and inspiration for future research.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

MATHEMATICAL MODELING AND BIFURCATION ANALYSIS FOR A BIOLOGICAL MECHANISM OF CANCER DRUG RESISTANCE

Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.

Ultra-conservative noncoding RNA uc.243 confers chemo-resistance by facilitating the efflux of the chemotherapeutic drug in ovarian cancer

Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor survival.it has been found that non-coding RNAs(ncRNAs)not only participate in the transmission of signals between various cells but also participate in tumor immunity and anti-tumor immune responses,thereby regulating tumor occurrence and development.However,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still unclear.Methods:Western blotting assay,Quantitative real-time PCR analysis(qPCR),and Kaplan-Meier Plotter analysis were performed to analyze the expression and prognosis of uc.243 in ovarian carcinoma.Cytotoxicity assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer cells.RNA pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer cells.Results:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian cancer.Functional experiment displayed that uc.243 induced cisplatin resistance on ovarian cancer cells by facilitating the efflux of cisplatin(CDDP);but inhibiting the expression of uc.243 significantly reverses this function.Mechanistically,uc.243 can inhibit the binding of RNA binding protein DGCR8 microprocessor complex subunit to pri-miR-155,thereby inhibiting the cleavage of pri-miR-155 and decrease in mature miR-155,subsequently upregulates the expression of ATP binding cassette subfamily B member(ABCB1,ABCC2).Conclusion:Our research findings indicate that uc.243 can induce chemotherapy resistance in ovarian cancer,suggesting that it may become a new prognostic biomarker for malignant ovarian cancer.

Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis

Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

Research progress in tumor angiogenesis and drug resistance in breast cancer

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

Impact of the economic crisis and drug shortage on Lebanese cancer patients’care

BACKGROUND As a consequence of the economic crisis,the sociopolitical instability and the advent of the coronavirus disease-19 pandemic,nested challenges faced the Lebanese healthcare system.These have resulted in critical shortages of essential resources,including medications vital for oncologic patients.AIM To assess the ramifications of the ongoing economic crisis on oncology patient care focusing on our outpatient oncology department.METHODS A questionnaire was distributed during the month of February 2022 to oncology patients in Hôtel Dieu de France University Hospital in Beirut during their outpatient therapy.The primary objective was to assess the far-reaching impact of the economic crisis on patient care and the resulting psychological implications.RESULTS Among 182 interviewed patients,31.87%experienced treatment interruption mainly due to acute drug shortages.Despite 87.91%of the patients benefiting from third-party coverage,69.60%had to self-pay for their medications leading to 69.78%of patients perceiving that healthcare was more difficult to access after 2020.Psychologically,one-third of the patients exhibited symptoms of anxiety and/or depression,with 7 patients reporting suicidal ideations.Notably,37.93%of patients who interrupted cancer treatment reported a history of comorbidities,and 89.66%who altered their treatment cited financial difficulties.CONCLUSION Lebanese cancer patients face complex challenges spanning economic,healthcare,and psychological realms.Income inequalities exacerbated by the economic crisis hindered healthcare access.

Drug-Drug Interactions in Patients with Breast Cancer

The research paper investigates the intricate landscape of drug-drug interactions (DDIs) within the context of breast cancer treatment, with a particular focus on the elderly population and the use of complementary and alternative medicine (CAM). The study underscores the heightened susceptibility of elderly patients to DDIs due to the prevalence of polypharmacy and the widespread utilization of CAM among breast cancer patients. The potential ramifications of DDIs, encompassing adverse drug events and diminished treatment efficacy, are elucidated. The paper accentuates the imperative for healthcare providers to comprehensively understand both conventional and CAM therapies, enabling them to provide patients with informed guidance regarding safe and efficacious treatment options, culminating in enhanced patient outcomes.

Pembrolizumab-induced psoriatic arthritis treated with disease-modifying anti-rheumatic drugs in a patient with gastric cancer:A case report

BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.

Advances in Transdermal Drug Delivery for Cancer Therapy

Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.

Discussion on gemcitabine combined with targeted drugs in the treatment of pancreatic cancer

Pancreatic cancer is a malignant tumor with poor prognosis.The treatment of pancreatic cancer depends on the tumor stage and type,and includes local treatment(surgery,radiotherapy and ablation intervention)and systemic therapy(chemotherapy,targeted therapy and immunotherapy).We read with great interest the review“Effective combinations of anti-cancer and targeted drugs for pancreatic cancer treatment”published on World J Gastroenterol and intended to share some of our perspectives in pancreatic cancer treatment.This review presents the therapeutic effects of the combination of gemcitabine and targeted drugs,which gives us a deeper insight into the combination treatments for pancreatic cancer.

Antibody-Coupled Drugs in HER2-Positive Gastric Cancer

Antibody drug conjugates (ADCs) are a new class of drugs that combine chemosynthetic drugs with antibody drugs through a linker. Antibody drug conjugates combine the targeting characteristics of traditional antibody drugs with the cytotoxic characteristics of small molecule drugs, while reducing the side effects of both drugs, making them a kind of “biological missile” and representing a relatively new and evolving class of anti-cancer drugs. Antibody-coupled drugs are currently used in many solid tumors, and this article reviews the clinical application of antibody-coupled drugs in HER2-positive gastric cancer.

Drug repositioning of disulfiram induces endometrioid epithelial ovarian cancer cell death via the both apoptosis and cuproptosis pathways

Various therapeutic strategies have been developed to overcome ovarian cancer.However,the prognoses resulting from these strategies are still unclear.In the present work,we screened 54 small molecule compounds approved by the FDA to identify novel agents that could inhibit the viability of human epithelial ovarian cancer cells.Among these,we identified disulfiram(DSF),an old alcohol-abuse drug,as a potential inducer of cell death in ovarian cancer.Mechanistically,DSF treatment significantly reduced the expression of the anti-apoptosis marker Bcell lymphoma/leukemia-2(Bcl-2)and increase the expression of the apoptotic molecules Bcl2 associated X(Bax)and cleaved caspase-3 to promote human epithelial ovarian cancer cell apoptosis.Furthermore,DSF is a newly identified effective copper ionophore,thus the combination of DSF and copper was used to reduce ovarian cancer viability than DSF single treatment.Combination treatment with DSF and copper also led to the reduced expression of ferredoxin 1 and loss of Fe-S cluster proteins(biomarkers of cuproptosis).In vivo,DSF and copper gluconate significantly decreased the tumor volume and increased the survival rate in a murine ovarian cancer xenograft model.Thus,the role of DSF revealed its potential for used as a viable therapeutic agent for the ovarian cancer.

Smart drug delivery systems to overcome drug resistance in cancer immunotherapy

Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.

Non-steroidal anti-inflammatory drugs in prevention of gastric cancer

Non-steroidal anti-inflammatory drugs （NSAIDs） including cydooxygenase 2 （COX-2） selective inhibitors, are potential agents for the chemoprevention of gastric cancer. Epidemiological and experimental studies have shown that NSAID use is associated with a reduced risk of gastric cancer although many questions remain unanswered such as the optimal dose and duration of treatment. The possible mechanisms for the suppressor effect of NSAIDs on carcinogenesis are the ability to induce apoptosis in epithelial cells and regulation of angiogenesis. Both COX-dependent and COX- independent pathways have a role in the biological activity of NSAIDs. Knowledge of how NSAIDs prevent neoplastic growth will greatly aid the design of better chemopreventive drugs and novel treatments for gastric cancer.

Non-steroidal anti-inflammatory drugs and statins in relation to colorectal cancer risk

AIM： To investigate the association between individual or combined use of non-steroidal anti-inflammatory drugs （NSAIDs） or statins and colorectal cancer risk.METHODS： In a population-based case-control study in women, we examined the association between NSAIDs and statin use and the risk of colorectal cancers. We further investigated whether the use of statins modifies the protective effect of NSAIDs. Female cases （n = 669）of colorectal cancer aged 50-74 years were identified from a storewide registry in Wisconsin during 1999-2001. Community control women （n = 1375） were randomly selected from lists of licensed drivers and Medicare beneficiaries. Medication use and risk factor information were gathered during a structured telephone interview. A multivariable logistic regression model was used to calculate odds ratio （OR） and 95% confidence interval （CI）.RESULTS： Overall, NSAIDs users had a 30% reduction in risk of colorectal cancer （95% CI： 0.56-0.88）. Statin use was not associated with colorectal cancer risk （OR = 1.17, 95% CI： 0.74-1.85）, regardless of structural type （lipophilic or hydrophilic）, duration of use, or recency. There was no evidence of an interaction between NSAIDs and statins and colorectal cancer risk （P-interaction = 0.28）.CONCLUSION： Although our results confirm the inverse association between NSAIDs use and colorectal cancer risk, they do not support a risk reduction in statin users, or an interaction effect of combined NSAIDs and statin use.

Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes

BACKGROUND A recently hypothesized cause of cell death called disulfidptosis has been linked to the expansion,emigration,and vascular rebuilding of cancer cells.Cancer can be treated by targeting the pathways that trigger cell death.AIM To discover the long non-coding RNA of the disulfidaptosis-related lncRNAs(DRLs),prognosis clinical survival,and treat patients with colorectal cancer with medications.METHODS Initially,we queried the Cancer Genome Atlas database to collect transcriptome,clinical,and genetic mutation data for colorectal cancer(CRC).Training and testing sets for CRC patient transcriptome data were generated randomly.Key long non-coding RNAs(lncRNAs)related to DRLs were then identified and evaluated using a least absolute shrinkage and selection operator procedure,as well as univariate and multivariate Cox regression models.A prognostic model was then created after risk scoring.Also,Immune infiltration analysis,immune checkpoint analysis,and medication susceptibility analysis were used to investigate the causes of the different prognoses between high and low risk groups.Finally,we validated the differential expression and biomarker potential of riskpredictive lncRNAs through induction using both NCM460 and HT-29 cell lines,as well as a disulfidptosis model.RESULTS In this work,eight significant lncRNAs linked to disulfidptosis were found.Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of differentially expressed genes between high-and low-risk groups from the prognostic model showed a close relationship with the immune response as well as significant enrichment in neutrophil extracellular trap formation and the IL-17 signaling pathway.Furthermore,significant immune cell variations between the high-risk and low-risk groups were seen,as well as a higher incidence of immunological escape risk in the high-risk group.Finally,Epirubicin,bortezomib,teniposide,and BMS-754807 were shown to have the lowest sensitivity among the four immunotherapy drugs.CONCLUSION Our findings emphasizes the role of disulfidptosis in regulating tumor development,therapeutic response,and patient survival in CRC patients.For the clinical treatment of CRC,these important LncRNAs could serve as viable therapeutic targets.