Exploration of targeted anti-tumor therapy最新文献

{"title":"Anticancer peptides as novel immunomodulatory therapeutic candidates for cancer treatment.","authors":"Apurva Sood, V V Jothiswaran, Amrita Singh, Anuradha Sharma","doi":"10.37349/etat.2024.00264","DOIUrl":"10.37349/etat.2024.00264","url":null,"abstract":"<p><p>Cancer remains a concern after years of research in this field. Conventional therapies such as chemotherapy, radiation, and surgery are available for cancer treatment, but they are characterized by various side effects. There are several immunological challenges that make it difficult for the immune system and conventional therapies to treat cancer. Some of these challenges include heterogeneity, resistance to medicines, and cancer relapse. Even advanced treatments like immune checkpoint inhibitors (ICIs), which revolutionized cancer treatment, have associated toxicity and resistance further necessitate the exploration of alternative therapies. Anticancer peptides (ACPs) offer promising potential as cancer-fighting agents and address challenges such as treatment resistance, tumor heterogeneity, and metastasis. Although these peptides exist as components of the defense system in various plants, animals, fungi, etc., but can also be created synthetically and used as a new treatment measure. These peptides possess properties that make them appealing for cancer therapy, such as apoptosis induction, inhibition of angiogenesis, and cell membrane breakdown with low toxicity. Their capacity to specifically target cancer cells selectively holds promise for enhancing treatment environments as well as improving patients' quality of life. This review provides detailed insights into the different prospects of ACPs, including their characterization, use as immunomodulatory agents in cancer treatment, and their mechanistic details after addressing various immunological challenges in existing cancer treatment strategies. In conclusion, ACPs have promising potential as novel cancer therapeutics due to their target specificity and fewer side effects than conventional therapies.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"1074-1099"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging molecular therapies in the treatment of bladder cancer.","authors":"Scott D Bell, Anthony E Quinn, Tom D Spitzer, Brady B Voss, Mark R Wakefield, Yujiang Fang","doi":"10.37349/etat.2024.00267","DOIUrl":"10.37349/etat.2024.00267","url":null,"abstract":"<p><p>Bladder cancer is a leading cancer type in men. The complexity of treatment in late-stage bladder cancer after systemic spread through the lymphatic system highlights the importance of modulating disease-free progression as early as possible in cancer staging. With current therapies relying on previous standards, such as platinum-based chemotherapeutics and immunomodulation with Bacillus Calmette-Guerin, researchers, and clinicians are looking for targeted therapies to stop bladder cancer at its source early in progression. A new era of molecular therapies that target specific features upregulated in bladder cancer cell lines is surfacing, which may be able to provide clinicians and patients with better control of disease progression. Here, we discuss multiple emerging therapies including immune checkpoint inhibitors of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway, antibody-drug conjugates, modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) cell proliferation pathway, chimeric antigen receptor T-cell therapy, and fibroblast growth factor receptor targeting. Together, these modern treatments provide potentially promising results for bladder cancer patients with the possibility of increasing remission and survival rates.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"1135-1154"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospects for breast cancer immunotherapy using microRNAs and transposable elements as objects.","authors":"Rustam Nailevich Mustafin","doi":"10.37349/etat.2024.00261","DOIUrl":"10.37349/etat.2024.00261","url":null,"abstract":"<p><p>One of the directions in treatment of chemoresistant breast cancer (BC) may include new methods of activating the immune response against tumor cells. Clinically used checkpoint inhibition using antibodies to PD-1 and PD-L1 works in some patients, but the lack of biomarkers means number of respondents is low. The possibility of combining this method with chemotherapy is limited by an increased risk of toxic liver damage, development of immune-related pneumonitis, and thyroid dysfunction. This article includes introduction into the clinic of new methods of immunotherapy for BC, among which epigenetic activation of retroelements, double-stranded transcripts of which stimulate the interferon response against the tumor, is promising. For this purpose, inhibitors of DNA methyltransferase*, histone deacetylase* and histone methyltransferase* are used (* subtitles in the main text). Their antitumor effect is also mediated by removal of repressive epigenetic marks from tumor suppressor genes. However, numerous studies have proven the role of retroelements in the carcinogenesis of various malignant neoplasms, including BC. Moreover, endogenous retroviruses HERV-K and LINE1 retrotransposons are planned to be used as diagnostic biomarkers for BC. Therefore, a rational approach to using viral mimicry in antitumor therapy of BC may be the simultaneous suppression of specific retrotransposons (drivers for carcinogenesis) using reverse transcriptase inhibitors and silencing of specific transposons involved in carcinogenesis using complementary microRNAs. To determine possible pathways of influence in this direction, 35 specific transposon-derived microRNAs* changes in BC were identified, which can become guides for targeted therapy of BC.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"1011-1026"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative peritumoral magnetic resonance imaging fingerprinting improves machine learning-based prediction of overall survival in colorectal cancer.","authors":"Azadeh Tabari, Brian D'Amore, Janice Noh, Michael S Gee, Dania Daye","doi":"10.37349/etat.2024.00205","DOIUrl":"10.37349/etat.2024.00205","url":null,"abstract":"<p><strong>Aim: </strong>To investigate magnetic resonance imaging (MRI)-based peritumoral texture features as prognostic indicators of survival in patients with colorectal liver metastasis (CRLM).</p><p><strong>Methods: </strong>From 2007-2015, forty-eight patients who underwent MRI within 3 months prior to initiating treatment for CRLM were identified. Clinicobiological prognostic variables were obtained from electronic medical records. Ninety-four metastatic hepatic lesions were identified on T1-weighted post-contrast images and volumetrically segmented. A total of 112 radiomic features (shape, first-order, texture) were derived from a 10 mm region surrounding each segmented tumor. A random forest model was applied, and performance was tested by receiver operating characteristic (ROC). Kaplan-Meier analysis was utilized to generate the survival curves.</p><p><strong>Results: </strong>Forty-eight patients (male:female = 23:25, age 55.3 years ± 18 years) were included in the study. The median lesion size was 25.73 mm (range 8.5-103.8 mm). Microsatellite instability was low in 40.4% (38/94) of tumors, with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>) mutation detected in 68 out of 94 (72%) tumors. The mean survival was 35 months ± 21 months, and local disease progression was observed in 35.5% of patients. Univariate regression analysis identified 42 texture features [8 first order, 5 gray level dependence matrix (GLDM), 5 gray level run time length matrix (GLRLM), 5 gray level size zone matrix (GLSZM), 2 neighboring gray tone difference matrix (NGTDM), and 17 gray level co-occurrence matrix (GLCM)] independently associated with metastatic disease progression (<i>P</i> < 0.03). The random forest model achieved an area under the curve (AUC) of 0.88.</p><p><strong>Conclusions: </strong>MRI-based peritumoral heterogeneity features may serve as predictive biomarkers for metastatic disease progression and patient survival in CRLM.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"74-84"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD99 tumor associated antigen is a potential target for antibody therapy of T-cell acute lymphoblastic leukemia.","authors":"Kamonporn Kotemul, Watchara Kasinrerk, Nuchjira Takheaw","doi":"10.37349/etat.2024.00207","DOIUrl":"10.37349/etat.2024.00207","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) are an effective drug for targeted immunotherapy in several cancer types. However, so far, no antibody has been successfully developed for certain types of cancer, including T-cell acute lymphoblastic leukemia (T-ALL). T-ALL is an aggressive hematologic malignancy. T-ALL patients who are treated with chemotherapeutic drugs frequently relapse and become drug resistant. Therefore, antibody-based therapy is promising for T-ALL treatment. To successfully develop an antibody-based therapy for T-ALL, antibodies that induce death in malignant T cells but not in nonmalignant T cells are required to avoid the induction of secondary T-cell immunodeficiency. In this review, CD99 tumor associated antigen, which is highly expressed on malignant T cells and lowly expressed on nonmalignant T cells, is proposed to be a potential target for antibody therapy of T-ALL. Since certain clones of anti-CD99 mAbs induce apoptosis only in malignant T cells, these anti-CD99 mAbs might be a promising antibody drug for the treatment of T-ALL with high efficiency and low adverse effects. Moreover, over the past 25 years, many clones of anti-CD99 mAbs have been studied for their direct effects on T-ALL. These outcomes are gathered here.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"96-107"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical implications of androgen receptor inhibitors for prostate cancer treatment.","authors":"Fabio Campodonico, Luca Foppiani, Vittoria Campodonico, Carlo Introini","doi":"10.37349/etat.2024.00234","DOIUrl":"10.37349/etat.2024.00234","url":null,"abstract":"<p><p>Antiandrogens have been used for the treatment of prostate cancer as a single agent or in combination with hormone deprivation therapy. New generation antiandrogens act like androgen receptor inhibitors (ARIs). Their binding complex blocks the pathways of cellular proliferation and differentiation of the prostate. Enzalutamide, apalutamide and darolutamide are the new ARIs that demonstrated acceptable tolerability and toxicity, both active in hormone-sensitive and castration-resistant prostate cancer (CRPC). There is no evidence of superiority of one drug over the other, therefore the therapeutic choice depends on the safety profile in relation to the individual patient, their comorbidities and clinical condition. ARIs have also shown promising results in association with new drugs that are active on patients with metastatic CRPC carrying the mutated breast cancer gene (<i>BRCA</i>). Before undergoing new antiandrogenic therapies, patients should be evaluated for cardiological and metabolic risk and possible drug interactions.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"543-550"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells.","authors":"Yamila Sanchez, Mariana Abigail Vasquez Callejas, Noelia Victoria Miret, Gabino Rolandelli, Catalina Costas, Andrea Silvana Randi, Alejandro Español","doi":"10.37349/etat.2024.00218","DOIUrl":"10.37349/etat.2024.00218","url":null,"abstract":"<p><strong>Aim: </strong>Triple negative breast cancer (TNBC) is usually treated with high doses of paclitaxel, whose effectiveness may be modulated by the action of environmental contaminants such as hexachlorobenzene. High doses of paclitaxel cause adverse effects such as low cellular selectivity and the generation of resistance to treatment due to an increase in the expression of multidrug resistance proteins (MRPs). These effects can be reduced using a metronomic administration scheme with low doses. This study aimed to investigate whether hexachlorobenzene modulates the response of cells to conventional chemotherapy with paclitaxel or metronomic chemotherapy with paclitaxel plus carbachol, as well as to study the participation of the MRP ATP-binding cassette transporter G2 (ABCG2) in human TNBC MDA-MB231 cells.</p><p><strong>Methods: </strong>Cells were treated with hexachlorobenzene alone or in combination with conventional or metronomic chemotherapies. The effects of treatments on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the nuclear factor kappa B pathway participation was evaluated using a selective inhibitor. ABCG2 expression and its modulation were determined by western blot.</p><p><strong>Results: </strong>Results confirmed that paclitaxel reduces MDA-MB231 cell viability in a concentration-dependent manner. Results also showed that both conventional and metronomic chemotherapies reduced cell viability with similar efficacy. Although hexachlorobenzene did not modify cell viability <i>per se</i>, it did reverse the effect induced by the conventional chemotherapy, without affecting the efficacy of the metronomic chemotherapy. Additionally, a differential modulation of ABCG2 expression was determined, mediated by the nuclear factor kappa B pathway, which was directly related to the modulation of cell sensitivity to another cycle of paclitaxel treatment.</p><p><strong>Conclusions: </strong>The findings indicate that, in human TNBC MDA-MB231 cells, in the presence of hexachlorobenzene, the metronomic combination of paclitaxel plus carbachol is more effective in affecting the tumor biology than the conventional therapeutic administration scheme of paclitaxel.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 2","pages":"278-295"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring monocarboxylate transporter inhibition for cancer treatment.","authors":"Tomas Koltai, Larry Fliegel","doi":"10.37349/etat.2024.00210","DOIUrl":"10.37349/etat.2024.00210","url":null,"abstract":"<p><p>Cells are separated from the environment by a lipid bilayer membrane that is relatively impermeable to solutes. The transport of ions and small molecules across this membrane is an essential process in cell biology and metabolism. Monocarboxylate transporters (MCTs) belong to a vast family of solute carriers (SLCs) that facilitate the transport of certain hydrophylic small compounds through the bilipid cell membrane. The existence of 446 genes that code for SLCs is the best evidence of their importance. In-depth research on MCTs is quite recent and probably promoted by their role in cancer development and progression. Importantly, it has recently been realized that these transporters represent an interesting target for cancer treatment. The search for clinically useful monocarboxylate inhibitors is an even more recent field. There is limited pre-clinical and clinical experience with new inhibitors and their precise mechanism of action is still under investigation. What is common to all of them is the inhibition of lactate transport. This review discusses the structure and function of MCTs, their participation in cancer, and old and newly developed inhibitors. Some suggestions on how to improve their anticancer effects are also discussed.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"135-169"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of primary and passaged tumor cell cultures and their application in personalized medicine.","authors":"Vladislava V Pipiya, Zarema E Gilazieva, Shaza S Issa, Albert A Rizvanov, Valeriya V Solovyeva","doi":"10.37349/etat.2024.00237","DOIUrl":"10.37349/etat.2024.00237","url":null,"abstract":"<p><p>Passaged cell lines represent currently an integral component in various studies of malignant neoplasms. These cell lines are utilized for drug screening both in monolayer cultures or as part of three-dimensional (3D) tumor models. They can also be used to model the tumor microenvironment in vitro and in vivo through xenotransplantation into immunocompromised animals. However, immortalized cell lines have some limitations of their own. The homogeneity of cell line populations and the extensive passaging in monolayer systems make these models distant from the original disease. Recently, there has been a growing interest among scientists in the use of primary cell lines, as these are passaged directly from human tumor tissues. In this case, cells retain the morphological and functional characteristics of the tissue from which they were derived, an advantage often not observed in passaged cultures. This review highlights the advantages and limitations of passaged and primary cell cultures, their similarities and differences, as well as existing test systems that are based on primary and passaged cell cultures for drug screening purposes.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"581-599"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promising immunotherapeutic approaches for primary effusion lymphoma.","authors":"Jutatip Panaampon, Seiji Okada","doi":"10.37349/etat.2024.00242","DOIUrl":"10.37349/etat.2024.00242","url":null,"abstract":"<p><p>Primary effusion lymphoma (PEL) is a large B-cell neoplasm usually presenting as a serious effusion in body cavities without detectable tumor masses. It is an AIDS-related non-Hodgkin's lymphoma (HL) with human herpes virus 8 (HHV8)/Kaposi sarcoma-associated herpes virus (KSHV) infection. A combination antiretroviral therapy (cART) prolongs the lifespan of AIDS and AIDS-related malignant lymphoma patients, but PEL continues to have a dismal prognosis. PEL showed disappointing outcomes with standard chemotherapy such as CHOP or CHOP-like regimens. A PEL status highlights the urgent need for new therapeutic approaches and treatment strategies and improve clinical outcomes. This review discusses the current knowledge and some recent clinical trials for PEL in the platform of immunotherapy as well as promising future immunotherapeutic approaches for PEL.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"699-713"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}