Exploration of targeted anti-tumor therapy最新文献

{"title":"Addressing the unmet need in NSCLC progression with advances in second-line therapeutics.","authors":"Kinsley Wang, Alexis Leyba, Robert Hsu","doi":"10.37349/etat.2024.00277","DOIUrl":"https://doi.org/10.37349/etat.2024.00277","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer mortality globally, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Despite advancements in first-line treatments such as immunotherapy and targeted therapies, resistance to these treatments is common, creating a significant unmet need for effective second-line therapies. This review evaluates current and emerging second-line therapeutic options for advanced or metastatic NSCLC, focusing on their efficacy and potential to improve patient outcomes. Anti-angiogenic drugs like ramucirumab combined with chemotherapy, particularly docetaxel, have shown moderate success. Antibody-drug conjugates (ADCs) targeting specific tumor antigens offer a promising avenue for targeted therapy, while chimeric antigen receptor (CAR)-T cell therapy and T-cell receptor therapy leverage the patient's immune system to combat cancer more effectively. mRNA vaccines, although in early stages, show potential for inducing robust immune responses against cancer-specific antigens. Building on this foundation, recent advancements in molecular testing and the exploration of the tumor microenvironment are opening new therapeutic avenues, further enhancing the potential for personalized second-line treatments in NSCLC. While ADCs and bispecific antibodies are gaining traction, more precise biomarkers are needed to optimize treatment response. Regular monitoring through techniques like liquid biopsies allows real-time tracking of mutations such as EGFR T790M, enabling timely therapeutic adjustments. Additionally, the role of neutrophils and macrophages in the tumor microenvironment is increasingly being recognized as a potential therapeutic avenue, with Smad3 emerging as a key target. Further research into drug sequencing, toxicity management, and biomarker development remains crucial to improving NSCLC treatment outcomes.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1297-1320"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933993","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":"DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine.","authors":"Jingxin Ye, Jianfeng Zhang, Weifeng Ding","doi":"10.37349/etat.2024.00203","DOIUrl":"10.37349/etat.2024.00203","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a multifaceted disease influenced by the interplay of genetic and environmental factors. The clinical heterogeneity of CRC cannot be attributed exclusively to genetic diversity and environmental exposures, and epigenetic markers, especially DNA methylation, play a critical role as key molecular markers of cancer. This review compiles a comprehensive body of evidence underscoring the significant involvement of DNA methylation modifications in the pathogenesis of CRC. Moreover, this review explores the potential utility of DNA methylation in cancer diagnosis, prognostics, assessment of disease activity, and prediction of drug responses. Recognizing the impact of DNA methylation will enhance the ability to identify distinct CRC subtypes, paving the way for personalized treatment strategies and advancing precision medicine in the management of CRC.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"34-53"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095214","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":"Early-stage triple negative breast cancer: the therapeutic role of immunotherapy and the prognostic value of pathological complete response.","authors":"Pierluigi De Santis, Martina Perrone, Chiara Guarini, Anna Natalizia Santoro, Carmelo Laface, Daniela Carrozzo, Gaia Rachele Oliva, Palma Fedele","doi":"10.37349/etat.2024.00215","DOIUrl":"10.37349/etat.2024.00215","url":null,"abstract":"<p><p>Triple negative breast cancer (TNBC) represents an aggressive disease associated with a high risk of recurrence after curative treatment and a poor prognosis in the metastatic setting. Chemotherapy was for years the only treatment available in the early and metastatic setting, due to the lack of actionable targets. Clinical practice has changed following the results obtained with the addition of immunotherapy to standard chemotherapy, the development of novel drugs [i.e. antibody-drug conjugates (ADCs)], and the use of targeted treatments for patients carrying germline pathogenic breast cancer susceptibility genes (<i>BRCA</i>) <i>1</i> or <i>BRCA 2</i> variants. The treatment of early-stage disease has had a shift in clinical practice since July 2021, after the Food and Drug Administration (FDA) approval of pembrolizumab in association with chemotherapy as neoadjuvant treatment for TNBC and as a single agent in the subsequent adjuvant setting. This intensive treatment based on the combination of a poly-chemotherapy and an immune checkpoint inhibitor (ICI) led to the improvement of short- and long-term outcomes, but it has highlighted some new unmet clinical needs in the treatment of early-stage TNBC: the selection of the most effective adjuvant therapy and the integration of pembrolizumab with other therapeutic strategies [capecitabine, poly(ADP-ribose) polymerase (PARP) inhibitors] based on the achievement of pathologic complete response (pCR); the identification of predictive biomarkers to select patients who could most benefit from the addition of ICI, to minimize toxicities and to maximize outcomes; the possibility of de-escalating chemotherapy in favor of immune-combo or novel agents, such as ADCs; the role of immunotherapy in estrogen receptor (ER)-low patients. The advent of immunotherapy not only addresses current challenges in TNBC treatment but also holds the promise of a radical transformation in its therapeutic paradigm, enhancing significantly clinical outcomes and offering new perspectives for patients grappling with this aggressive form of breast cancer.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"232-250"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095215","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":"Management of stage III non-small-cell lung cancer: rays of hope.","authors":"Floryane Kim, Maxime Borgeaud, Alfredo Addeo, Alex Friedlaender","doi":"10.37349/etat.2024.00206","DOIUrl":"10.37349/etat.2024.00206","url":null,"abstract":"<p><p>Lung cancer remains the most common cause of cancer death across the world. Non-small-cell lung cancer (NSCLC) represents the most frequent type of lung cancer and is frequently diagnosed at an advanced stage. Stage III NSCLC, which encompasses 30% of cases, refers to a state between localized and metastatic disease, and is associated with poor prognosis. As highlighted in this review, stage III represents a heterogenous group, whose complex management includes multimodal treatment, discussed below, and requires discussion in multidisciplinary teams. The goal of this approach is a maximalist attitude in these patients with locally advanced and non-metastatic disease. However, many issues remain under debate including the optimal sequences of treatment between different treatment modalities, patient selection particularly for surgery, the duration of perioperative treatments and the identification of biomarkers to determine which patients might benefit of specific treatment like immunotherapy and targeted therapies. This review describes the current landscape of management of stage III NSCLC, discussing the critical issue of resectability, and highlighting the recent advancements in the field, particularly the incorporation of immune-checkpoint inhibitors (ICIs) and targeted therapies in this setting.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"85-95"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095252","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":"Current status of molecular diagnostics for lung cancer.","authors":"Evgeny N Imyanitov, Elena V Preobrazhenskaya, Sergey V Orlov","doi":"10.37349/etat.2024.00244","DOIUrl":"10.37349/etat.2024.00244","url":null,"abstract":"<p><p>The management of lung cancer (LC) requires the analysis of a diverse spectrum of molecular targets, including kinase activating mutations in <i>EGFR</i>, <i>ERBB2</i> (<i>HER2</i>), <i>BRAF</i> and <i>MET</i> oncogenes, <i>KRAS</i> G12C substitutions, and <i>ALK</i>, <i>ROS1</i>, <i>RET</i> and <i>NTRK1-3</i> gene fusions. Administration of immune checkpoint inhibitors (ICIs) is based on the immunohistochemical (IHC) analysis of PD-L1 expression and determination of tumor mutation burden (TMB). Clinical characteristics of the patients, particularly age, gender and smoking history, significantly influence the probability of finding the above targets: for example, LC in young patients is characterized by high frequency of kinase gene rearrangements, while heavy smokers often have <i>KRAS</i> G12C mutations and/or high TMB. Proper selection of first-line therapy influences overall treatment outcomes, therefore, the majority of these tests need to be completed within no more than 10 working days. Activating events in MAPK signaling pathway are mutually exclusive, hence, fast single-gene testing remains an option for some laboratories. RNA next-generation sequencing (NGS) is capable of detecting the entire repertoire of druggable gene alterations, therefore it is gradually becoming a dominating technology in LC molecular diagnosis.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"742-765"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536157","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":"Combination of the PARPi and ARSi in advanced castration resistant prostate cancer: a review of the recent phase III trials.","authors":"Martina Panebianco, Vittore Cereda, Mario Rosario D'Andrea","doi":"10.37349/etat.2024.00260","DOIUrl":"10.37349/etat.2024.00260","url":null,"abstract":"<p><p>Tumors with an impaired ability to repair DNA double-strand breaks by homologous recombination, including those with alterations in breast cancer 1 and 2 (<i>BRCA1</i> and <i>BRCA2</i>) genes, are very sensitive to blocking DNA single-strand repair by inhibition of the poly (ADP-ribose) polymerase (PARP) enzyme. This provides the basis for a synthetic deadly strategy in the treatment of different types of cancer, such as prostate cancer (PCa). The phase 3 PROfound study was the first to lead to olaparib approval in patients with metastatic castration resistant PCa (mCRPC) and <i>BRCA</i> genes mutations. In recent years, the benefit of combination therapy consisted of a PARP inhibitor (PARPi) plus an androgen receptor signalling inhibitor (ARSi), was evaluated as first-line treatment of mCRPC, regardless of the mutational state of genes, participating in the homologous recombination repair (HRR). This review explores the role of PARPi in PCa and analyses the data of latest clinical trials exploring the PARPi-ARSi combinations, and how these results could change our clinical practice.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"997-1010"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333754","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":"GPCRs as targets for flavonoids in cancer cells: new options for intervention.","authors":"Katrin Sak","doi":"10.37349/etat.2024.00268","DOIUrl":"10.37349/etat.2024.00268","url":null,"abstract":"<p><p>For a long time, the family of receptor tyrosine kinases, including epidermal growth factor receptor and insulin-like growth factor 1 receptor, was regarded as the main players stimulating cell proliferative signaling. Today, it is increasingly clear that many G protein-coupled receptors (GPCRs) are also involved in controlling the hallmarks of cancer by activating diverse intracellular signaling networks. GPCRs can therefore be considered as promising drug targets for fighting against diverse types of human malignancies. Although plant polyphenols, flavonoids, are well known for their diverse anticancer effects inhibiting the growth, proliferation, migration, and invasion of malignant cells, involvement of GPCRs in these activities has still remained largely unelucidated. Therefore, in this review article, the current knowledge about the role of GPCRs in anticancer action of structurally varied flavonoids is compiled, highlighting the ability of these natural polyphenols to modulate the expression levels of GPCRs but also suppress the action of endogenous ligands and downstream tumor-promoting events. These data show that targeting the respective GPCRs by specific flavonoids may open new perspectives in the therapeutic intervention in human malignancies.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1155-1167"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516779","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":"Preliminary evaluation of FAPI-04-PET/CT for differentiating recurrence and post-treatment changes in high-grade gliomas.","authors":"Indraja D Dev, Ameya D Puranik, Venkatesh Rangarajan, Sukriti Patra, Nilendu Purandare, Arpita Sahu, Amitkumar Choudhary, Kajari Bhattacharya, Tejpal Gupta, Abhishek Chatterjee, Archya Dasgupta, Aliasgar Moiyadi, Prakash Shetty, Vikas Singh, Epari Sridhar, Ayushi Sahay, Aekta Shah, Suchismita Ghosh, Sayak Choudhury, Sneha Shah, Archi Agrawal","doi":"10.37349/etat.2024.00276","DOIUrl":"https://doi.org/10.37349/etat.2024.00276","url":null,"abstract":"<p><p>Fibroblast-activated protein (FAP) expression in glial cells is attributed to FAP-positive foci on tumor vessels and neoplastic cells. Preclinical and pilot studies have shown FAP expression in high-grade gliomas. We aimed at comparing PET imaging with FAP-inhibitor (FAPI-PET) with current standard, i.e., fluoro-ethyl tyrosine (FET) PET in post-treatment setting to differentiate recurrence and post-treatment changes. 6 patients with WHO Grade III and IV glioma who received standard treatment underwent Ga-68-FAPI-04 PET/CT (FAPI-PET/CT). Tracer uptake greater than background was considered positive. FET PET was performed and interpreted as per institutional standards, which formed the basis of treatment decision. There was concordance between FAPI expression and FET uptake in 5 patients suggestive of disease recurrence. There was no FAPI expression seen in 1 patient, in whom FET PET was suggestive of post-treatment changes. FAPI PET uptake correlated with amino acid expression to differentiate post treatment changes from recurrence in high-grade glial tumors; further validation with prospective study and histopathological confirmation is needed.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1289-1296"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933994","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":"Harnessing endoscopic ultrasound-guided radiofrequency ablation to reshape the pancreatic ductal adenocarcinoma microenvironment and elicit systemic immunomodulation.","authors":"Vishali Moond, Bhumi Maniyar, Prateek Suresh Harne, Jennifer M Bailey-Lundberg, Nirav C Thosani","doi":"10.37349/etat.2024.00263","DOIUrl":"10.37349/etat.2024.00263","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognostics and substantial therapeutic challenges, with dismal survival rates. Tumor resistance in PDAC is primarily attributed to its fibrotic, hypoxic, and immune-suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA), an Food and Drug Administration (FDA)-approved minimally invasive technique for treating pancreatic cancer, disrupts tumors with heat and induces coagulative necrosis, releasing tumor antigens that may trigger a systemic immune response-the abscopal effect. We aim to elucidate the roles of EUS-RFA-mediated thermal and mechanical stress in enhancing anti-tumor immunity in PDAC. A comprehensive literature review focused on radiofrequency immunomodulation and immunotherapy in pancreatic tumors to understand the pathophysiological mechanisms of RFA and its effect on the TME, which could prevent recurrence and resistance. We reviewed clinical, preclinical, and <i>in vitro</i> studies on RFA mechanisms in pancreatic adenocarcinoma, discussing the unique immunomodulatory effects of EUS-RFA. Recent findings suggest that combining RFA with immune adjuvants enhances responses in pancreatic adenocarcinoma. EUS-RFA offers a dual benefit against PDAC by directly reducing tumor viability and indirectly enhancing anti-tumor immunity. Observations of neutrophil-mediated immunomodulation and programmed cell death ligand 1 (PD-L1) modulation support integrating EUS-RFA with targeted immunotherapies for managing pancreatic adenocarcinoma. Integrating EUS-RFA in PDAC treatment promises direct cytoreduction and synergistic effects with molecular targeted therapies. Prospective clinical trials are crucial to assess the efficacy of this combined approach in improving outcomes and survival rates in advanced PDAC cases.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"1056-1073"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333757","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":"Diagnostic and prognostic role of NLR in testicular cancer.","authors":"Shirin Sarejloo, Saghar Babadi, Shokoufeh Khanzadeh, Amirhossein Salimi, Alec Clark, Dinyar Khazaeli, Monireh Khanzadeh, Arshin Ghaedi, Brandon Lucke-Wold","doi":"10.37349/etat.2024.00270","DOIUrl":"10.37349/etat.2024.00270","url":null,"abstract":"<p><strong>Background: </strong>To summarize the results of available studies for investigating the role of neutrophil to lymphocyte ratio (NLR) in testicular cancer (tCa).</p><p><strong>Methods: </strong>The search was conducted on PubMed, Scopus, and Web of Science up to November 21, 2021. Finally, a total of 31 studies were included in this review.</p><p><strong>Results: </strong>NLR was higher in tCa patients compared to healthy controls and benign testis pathologies, and decreased significantly after orchiectomy. An elevated NLR predicts poor prognosis, advanced stage, presence of nodal or distant metastases, contralateral tumor development, lower time-to-cancer specific death, worse OS, and poorer response to chemotherapy. However, NLR could not differentiate between seminomas and non-seminomatous tCa.</p><p><strong>Discussion: </strong>NLR has a significant diagnostic and prognostic value in tCa.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1177-1198"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514104","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}