Current Problems in Cancer最新文献

{"title":"Current and emerging strategies for the management of advanced/metastatic lung neuroendocrine tumors","authors":"Megan Rutherford ,&nbsp;Margaret Wheless ,&nbsp;Katharine Thomas ,&nbsp;Robert A. Ramirez","doi":"10.1016/j.currproblcancer.2024.101061","DOIUrl":"10.1016/j.currproblcancer.2024.101061","url":null,"abstract":"<div><p><span><span><span>Pulmonary neuroendocrine tumors<span> represent a spectrum of disease ranging from typical carcinoid tumors to </span></span>small cell lung cancers<span><span>. The incidence of low-grade pulmonary NETs has been increasing, leading to improved awareness and the need for more treatment options for this rare cancer. </span>Somatostatin analogs continue to be the </span></span>backbone<span><span><span> of therapy and may be followed or accompanied by targeted therapy, chemotherapy, and </span>immune therapy. The recent addition of </span>peptide receptor<span> radionuclide therapy (PRRT) to the treatment armamentarium of NETs has led to the development of targeted alpha therapy to overcome PRRT resistance and minimize off-target adverse effects. Herein, we aim to highlight current treatment options for patients with advanced low grade pulmonary NETs along with emerging therapies, sequencing of therapies, upcoming </span></span></span>clinical trials, and the importance of a multidisciplinary team to improve patient outcomes.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting RET alterations in non-small cell lung cancer","authors":"Go Nishikawa ,&nbsp;Mark A. Klein","doi":"10.1016/j.currproblcancer.2024.101074","DOIUrl":"10.1016/j.currproblcancer.2024.101074","url":null,"abstract":"<div><p>Rearranged during transfection (RET) alterations, which lead to aberrant activation of the <em>RET</em> proto-oncogene, have been identified in various cancers. In non-small cell lung cancer (NSCLC), <em>RET</em> mutations often manifest as <em>RET</em> fusion genes and are observed in 1–2 % of patients with NSCLC. In recent years, selective RET inhibitors such as selpercatinib and pralsetinib, approved by the Food and Drug Administration (FDA) in 2020, have been part of the revolutionary changes in the treatment landscape for non-small cell lung cancer. While first-generation RET inhibitors have become part of the standard of care for <em>RET</em>-fusion positive NSCLC, a new challenge has emerged: acquired resistance to RET inhibitors. RET resistance is a complex phenomenon that can manifest as either on-target or off-target resistance. Numerous studies have been conducted to identify the mechanisms behind this resistance. This review provides an overview of the biology of <em>RET</em> in NSCLC, methods of <em>RET</em> testing, and a comprehensive analysis of the clinical outcomes associated with multikinase and selective RET inhibitors for NSCLC. Additionally, we will explore future perspectives for <em>RET</em> fusion-positive NSCLC, including ongoing trials and the challenges involved in overcoming resistance to RET inhibitors.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting MEK in non-small cell lung cancer","authors":"Matthew S. Lara ,&nbsp;Collin M. Blakely ,&nbsp;Jonathan W. Riess","doi":"10.1016/j.currproblcancer.2024.101065","DOIUrl":"10.1016/j.currproblcancer.2024.101065","url":null,"abstract":"<div><p>The mitogen-activated protein kinase (MAPK or MEK) pathway modulates tumor cell survival and proliferation in non-small cell lung cancer (NSCLC). Unlike RAS or EGFR, activating mutations in MEK are exceedingly rare in NSCLC. Instead, enhanced activation of the MEK pathway is often linked to increased signaling by upstream oncogenic driver mutations. Thus far, MEK inhibitor monotherapy has shown little promise. However, treatment strategies involving MEK inhibition in combination with other targeted therapies in other oncogene-driven NSCLC has proven to be encouraging. For example, MEK inhibition - when combined with BRAF inhibition, - has shown strong anti-tumor activity in BRAF V600 mutated NSCLC. In this review, recent data on MEK inhibitor strategies in NSCLC are summarized. Furthermore, ongoing early phase trials investigating MEK inhibitor combination therapy with immunotherapy, chemotherapy and other oncogene drivers are highlighted. These and other studies could help inform future rational combination strategies of MEK-ERK inhibition in oncogene-driven NSCLC.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0147027224000060/pdfft?md5=7053f13c97ee7fcc94fc61e82de9cba0&pid=1-s2.0-S0147027224000060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effectiveness of lenalidomide/dexamethasone-based triplet regimens for treatment of relapsed and/or refractory multiple myeloma in the United States: An analysis of real-world electronic health records data","authors":"Sikander Ailawadhi ,&nbsp;Mu Cheng ,&nbsp;Dasha Cherepanov ,&nbsp;Maral DerSarkissian ,&nbsp;Dawn Marie Stull ,&nbsp;Annalise Hilts ,&nbsp;Justin Chun ,&nbsp;Mei Sheng Duh ,&nbsp;Larysa Sanchez","doi":"10.1016/j.currproblcancer.2024.101078","DOIUrl":"https://doi.org/10.1016/j.currproblcancer.2024.101078","url":null,"abstract":"<div><h3>Background</h3><p>This retrospective longitudinal study compared the effectiveness of dexamethasone+lenalidomide (Rd)-based triplet regimens containing proteasome inhibitors (PIs) ixazomib (IRd), carfilzomib (KRd), and bortezomib (VRd) or monoclonal antibodies (MABs) elotuzumab (ERd) and daratumumab (DRd) in patients with relapsed/refractory multiple myeloma (RRMM)—including those with high cytogenetic risk—primarily treated at community oncology clinics in the United States.</p></div><div><h3>Methods</h3><p>Electronic health records of adult RRMM patients in a deidentified real-world database (01/01/2014–09/30/2020) who initiated IRd, KRd, VRd, ERd, or DRd in the second or later line of therapy (LOT) were analyzed. The index date was the date of initiation of each LOT and baseline was the 6-month pre-index period. Duration of therapy (DOT), time to next therapy (TTNT), progression-free survival (PFS), and overall survival (OS) were compared across regimens with multivariable Cox proportional hazards models.</p></div><div><h3>Results</h3><p>Of the 1,185 patients contributing 1,332 LOTs, 985 had standard cytogenetic risk (median age, 71 years) and 180 had high risk (median age, 69 years). Compared with other regimens, DRd was associated with longer DOT overall (adjusted hazard ratio [95 % confidence interval]: 1.84 [1.42, 2.38] vs. KRd, 1.65 [1.20, 2.28] vs. ERd, 1.58 [1.23, 2.04] vs. IRd, and 1.54 [1.18, 2.00] vs. VRd), and longer TTNT and PFS. KRd was associated with shorter OS compared with DRd (1.45 [1.01, 2.08]) and VRd (1.32 [1.01, 1.73]). High-risk patients had similar outcomes with all triplet regimens.</p></div><div><h3>Conclusion</h3><p>Although DRd improved clinical outcomes overall, Rd-based triplet regimens containing a PI or MAB are similarly effective in high-risk RRMM.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of selinexor for patients with relapsed and refractory multiple myeloma: A meta-analysis","authors":"Laila Shafei ,&nbsp;Shaima Bashir ,&nbsp;Esther W. Chan ,&nbsp;Dina Abushanab ,&nbsp;Anas Hamad ,&nbsp;Daoud Al-Badriyeh","doi":"10.1016/j.currproblcancer.2024.101076","DOIUrl":"https://doi.org/10.1016/j.currproblcancer.2024.101076","url":null,"abstract":"<div><h3>Purpose</h3><p>Selinexor is a first-in-class, oral selective-inhibitor-of-nuclear-export, granted accelerated approval by FDA (2019) for relapsed and refractory multiple myeloma (RRMM). We sought to quantitatively summarize the selinexor efficacy and safety in RRMM.</p></div><div><h3>Methods</h3><p>We searched PubMed, EMBASE, CENTRAL, clinicaltrial.gov, and google scholar, until May 2023, studies about selinexor use in RRMM. The outcome measures of interest were primarily efficacy outcomes, in addition to safety outcomes. Random-effect model analyses were performed, at statistical significance of P&lt;0.05, using the RevMan software.</p></div><div><h3>Results</h3><p>Meta-analyses of eleven included clinical trials yielded a significant 56.21% overall clinical benefit, 46.91% overall response, 4.89% complete response, 23.41% very good partial response, 24.68% partial response, and 28.06% stable disease rates with selinexor. Due to safety reasons, selinexor caused significant increase in discontinuation rate, 16.80%. Subgroup analyses demonstrated higher efficacy with selinexor plus dexamethasone and proteasome inhibitor combinations than with selinexor alone. The multiple myeloma type, high cytogenetic risk, refractory state, and advanced disease state did not affect performance. Risk of selection, performance, and detection biases were unclear in the included trials.</p></div><div><h3>Conclusion</h3><p>Selinexor led to significant positive responses with an acceptable safety profile in RRMM patients, despite higher rates of safety-related discontinuations. Selinexor-based combinations further enhanced response.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140296641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of nomogram models for predicting postoperative prognosis of early-stage laryngeal squamous cell carcinoma","authors":"Xu Juan ,&nbsp;Huang Jiali ,&nbsp;Liu Ziqi ,&nbsp;Zhang Liqing ,&nbsp;Zhou Han","doi":"10.1016/j.currproblcancer.2024.101079","DOIUrl":"https://doi.org/10.1016/j.currproblcancer.2024.101079","url":null,"abstract":"<div><h3>Background</h3><p>We aimed to investigate the postoperative prognosis in patients with early-stage laryngeal squamous cell carcinoma (LSCC) in association with the preoperative blood markers and clinicopathological characteristics and to develop nomograms for individual risk prediction.</p></div><div><h3>Methods</h3><p>The clinical data of 353 patients with confirmed early-stage LSCC between 2009 and 2018 were retrospectively retrieved from the First Affiliated Hospital with Nanjing Medical University. All patients were randomly divided into the training and testing groups in a 7:3 ratio. Univariate and multivariate analyses were performed, followed by the construction of nomograms to predict recurrence-free survival (RFS) and overall survival (OS). Finally, the nomograms were verified internally, and the predictive capability of the nomograms was evaluated and compared with that of tumour T staging.</p></div><div><h3>Results</h3><p>Univariate and multivariate analyses identified platelet counts (PLT), fibrinogen (FIB), and platelet to lymphocyte ratio (PLR) were independent factors for RFS, and FIB, systemic immune-inflammation index (SII), and haemoglobin (HGB) were independent prognostic factors for OS. The nomograms showed higher predictive C-indexes than T staging. Furthermore, decision curve analysis (DCA) revealed that the net benefit of the nomograms’ calculation model was superior to that of T staging.</p></div><div><h3>Conclusions</h3><p>We established and validated nomograms to predict postoperative 1-, 3- and 5-year RFS and OS in patients with early-stage LSCC based on significant blood markers and clinicopathological characteristics. These models might help clinicians make personalized treatment decisions.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Title Page","authors":"","doi":"10.1016/S0147-0272(24)00010-2","DOIUrl":"https://doi.org/10.1016/S0147-0272(24)00010-2","url":null,"abstract":"","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140052392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of coenzyme Q10 as a preventive and therapeutic agent for the treatment of cancers","authors":"Ghazal Ghasempour Dabaghi ,&nbsp;Mehrdad Rabiee Rad ,&nbsp;Mahtab Mohammad-Zamani ,&nbsp;Atieh Karimi Shervedani ,&nbsp;Farnaz Bahrami-Samani ,&nbsp;Kiyan Heshmat-Ghahdarijani","doi":"10.1016/j.currproblcancer.2024.101063","DOIUrl":"10.1016/j.currproblcancer.2024.101063","url":null,"abstract":"<div><p>Currently, several options are available for the prevention and treatment of cancers; however, many limitations remain with these approaches. Recently, antioxidants have become important preventive and therapeutic alternatives with few adverse events and minimum cost. Coenzyme Q10 (CoQ10) is a naturally occurring component that performs an anticancer function by reducing oxidative stress. CoQ10 supplementation as an adjuvant therapy offers more progress in the elimination and development of cancers. This review aimed to critically assess and summarize the implication of CoQ10 in cancers, highlighting possible mechanisms, and future directions of research for the standardization of the current regimen for cancer prevention and treatment.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Information for Readers","authors":"","doi":"10.1016/S0147-0272(24)00011-4","DOIUrl":"https://doi.org/10.1016/S0147-0272(24)00011-4","url":null,"abstract":"","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140052393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of the peripheral blood lymphocyte/monocyte ratio combined with 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma","authors":"Wenke Wu ,&nbsp;Lidong Zhao ,&nbsp;Ying Wang ,&nbsp;Peng Chen ,&nbsp;Xiaoshuai Yuan ,&nbsp;Lei Miao ,&nbsp;Yuanxin Zhu ,&nbsp;Jianping Mao ,&nbsp;Zhimei Cai ,&nbsp;Yajun Ji ,&nbsp;Lei Wang ,&nbsp;Tao Jia","doi":"10.1016/j.currproblcancer.2024.101066","DOIUrl":"https://doi.org/10.1016/j.currproblcancer.2024.101066","url":null,"abstract":"<div><h3>Objective</h3><p>To explore the prognostic value of the peripheral blood lymphocyte/monocyte ratio (LMR) combined with ¹⁸F-FDG PET/CT for diffuse large B-cell lymphoma (DLBCL).</p></div><div><h3>Methods</h3><p>The clinical data of 203 patients with primary DLBCL who were hospitalized to the First People's Hospital of Lianyungang between January 2017 and December 2022 were retrospectively analyzed. Before and after three courses of treatment, PET/CT was performed on forty DLBCL patients. The subject operating characteristic (ROC) curve has been employed to determine the most effective LMR cutoff points. According to the criteria for assessing the efficacy of Lugano lymphoma, the PET/CT findings after 3 courses of treatment were specified as complete remission (CR), partial remission (PR), stable disease (SD) and disease progression (PD). The CR group, PR+SD group, and PD group were the three groups created from the four outcomes. Results were analyzed using the Cox proportional risk model, the Kaplan-Meier method (K-M), and the log-rank test.</p></div><div><h3>Results</h3><p>An optimal cutoff point of 3.00 for the LMR in 203 patients was determined by the SPSS 26 software ROC curve. When LMR≥3.00, the 1-year, 3-year, and 5-year OS (Overall Survival) rates are 98%, 88%, and 64% respectively, and the PFS (Progression-free Survival) rates are 90%, 75%, and 56% respectively. When LMR &lt;3.00, the 1-year, 3-year, and 5-year OS rates are 96%, 72%, and 28% respectively, and the PFS rates are 83%, 60%, and 28% respectively. A lower LMR was substantially related with shorter OS, and PFS, according to a K-M survival analysis (<em>P</em>&lt;0.005). LMR&lt;3.00 was an independent predictor of OS, based on a multifactorial Cox analysis (<em>P</em>=0.037). K-M survival analysis of the ¹⁸F-FDG PET/CT results of 40 patients revealed that both OS and PFS were statistically significant (<em>P</em>&lt;0.001). Patients were separated into 3 groups combining LMR and ¹⁸F-FDG PET/CT: PET/CT CR patients with LMR≥3.00, PET/CT PD patients with LMR&lt;3.00, and others. The Kaplan-Meier analysis revealed that there were significant differences in OS and PFS for each of the three groups (<em>P</em>&lt;0.001). ROC curves showed that the area under the curve (AUC) of the combined testing of the two was 0.735, and the combined testing of the two was better compared to testing alone (PET/CT AUC=0.535, LMR AUC=0.567). This indicates that combining both PET/CT and LMR is a favorable prediction for DLBCL.</p></div><div><h3>Conclusion</h3><p>A decreased LMR at initial diagnosis suggests an unfavorable prognosis for DLBCL patients; For patients with DLBCL, combining ¹⁸F-FDG PET/CT and the LMR has a better predictive value.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139743827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}