Journal of Cancer Metastasis and Treatment最新文献

{"title":"Targeting transcriptional regulators for treatment of anaplastic thyroid cancer.","authors":"Woo Kyung Lee,&nbsp;Sheue-Yann Cheng","doi":"10.20517/2394-4722.2021.58","DOIUrl":"https://doi.org/10.20517/2394-4722.2021.58","url":null,"abstract":"<p><p>Dysregulation of genes perpetuates cancer progression. During carcinogenesis, cancer cells acquire dependency of aberrant transcriptional programs (known as \"<i>transcription addiction</i>\") to meet the high demands for uncontrolled proliferation. The needs for particular transcription programs for cancer growth could be cancer-type-selective. The dependencies of certain transcription regulators could be exploited for therapeutic benefits. Anaplastic thyroid cancer (ATC) is an extremely aggressive human cancer for which new treatment modalities are urgently needed. Its resistance to conventional treatments and the lack of therapeutic options for improving survival might have been attributed to extensive genetic heterogeneity due to subsequent evolving genetic alterations and clonal selections during carcinogenesis. Despite this genetic complexity, mounting evidence has revealed a characteristic transcriptional addiction of ATC cells resulting in evolving diverse oncogenic signaling for cancer cell survival. The transcriptional addiction has presented a huge challenge for effective targeting as shown by the failure of previous targeted therapies. However, an emerging notion is that many different oncogenic signaling pathways activated by multiple upstream driver mutations might ultimately converge on the transcriptional responses, which would provide an opportunity to target transcriptional regulators for treatment of ATC. Here, we review the current understanding of how genetic alterations in cancer distorted the transcription program, leading to acquisition of transcriptional addiction. We also highlight recent findings from studies aiming to exploit the opportunity for targeting transcription regulators as potential therapeutics for ATC.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"7 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39610416","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":"Dietary phytochemicals and their role in cancer chemoprevention.","authors":"Shashank Kumar,&nbsp;Sanjay Gupta","doi":"10.20517/2394-4722.2021.125","DOIUrl":"https://doi.org/10.20517/2394-4722.2021.125","url":null,"abstract":"Epidemiological studies suggest a close association between diet and cancer initiation, which provides evidence that the dietary components may be effectively developed as chemopreventive agents[1]. These pieces of evidence are further supported by several case-control and cohort studies, which overwhelmingly support a converse association between the intake of phytochemicals and cancer risk[2,3]. A number of clinical studies have been conducted demonstrating that dietary phytochemicals have the ability to inhibit tumorigenesis[4]. Components present in fruit and vegetables termed “bioactive” phytochemicals belong to several classes of micronutrients, including flavonoids,","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"7 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39800477","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":"Multi-layered control of PD-L1 expression in Epstein-Barr virus-associated gastric cancer.","authors":"Christos N Miliotis,&nbsp;Frank J Slack","doi":"10.20517/2394-4722.2020.12","DOIUrl":"https://doi.org/10.20517/2394-4722.2020.12","url":null,"abstract":"<p><p>Gastric cancer (GC) is the fifth most common cancer worldwide. In approximately 10% of GC cases, cancer cells show ubiquitous and monoclonal Epstein-Barr virus (EBV) infection. A significant feature of EBV-associated GC (EBVaGC) is high lymphocytic infiltration and high expression of immune checkpoint proteins, including programmed death-ligand 1 (PD-L1). This highlights EBVaGC as a strong candidate for immune checkpoint blockade therapy. Indeed, several recent studies have shown that EBV positivity in GC correlates with positive response to programmed cell death protein 1 (PD-1)/PD-L1 blockade therapy. Understanding the mechanisms that control PD-L1 expression in EBVaGC can indicate new predictive biomarkers for immunotherapy, as well as therapeutic targets for combination therapy. Various mechanisms have been implicated in PD-L1 expression regulation, including structural variations, post-transcriptional control, oncogenic activation of intrinsic signaling pathways, and increased sensitivity to extrinsic signals. This review provides the most recent updates on the multilayered control of PD-L1 expression in EBVaGC.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 13","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39061320","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":"Negative effects of tumor cell nitric oxide on anti-glioblastoma photodynamic therapy.","authors":"Albert W Girotti, Jonathan M Fahey, Witold Korytowski","doi":"10.20517/2394-4722.2020.107","DOIUrl":"10.20517/2394-4722.2020.107","url":null,"abstract":"<p><p>Glioblastomas are highly aggressive brain tumors that can persist after exposure to conventional chemotherapy or radiotherapy. Nitric oxide (NO) produced by inducible NO synthase (iNOS/NOS2) in these tumors is known to foster malignant cell proliferation, migration, and invasion as well as resistance to chemo- and radiotherapy. Minimally invasive photodynamic therapy (PDT) sensitized by 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) is a highly effective anti-glioblastoma modality, but it is also subject to NO-mediated resistance. Studies by the authors have revealed that glioblastoma U87 and U251 cells use endogenous iNOS/NO to not only resist photokilling after an ALA/light challenge, but also to promote proliferation and migration/invasion of surviving cells. Stress-upregulated iNOS/NO was found to play a major role in these negative responses to PDT-like treatment. Our studies have revealed a tight network of upstream signaling events leading to iNOS induction in photostressed cells and transition to a more aggressive phenotype. These events include activation or upregulation of pro-survival/ pro-expansion effector proteins such as NF-κB, phosphoinositide-3-kinase (PI3K), protein kinase-B (Akt), p300, Survivin, and Brd4. In addition to this upstream signaling and its regulation, pharmacologic approaches for directly suppressing iNOS at its activity <i>vs.</i> transcriptional level are discussed. One highly effective agent in the latter category is bromodomain and extra-terminal (BET) inhibitor, JQ1, which was found to minimize iNOS upregulation in photostressed U87 cells. By acting similarly at the clinical level, a BET inhibitor such as JQ1 should markedly improve the efficacy of anti-glioblastoma PDT.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25351728","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":"Development of a Functional Assessment of Chronic Illness Therapy item library and primary symptom list for the assessment of patient-reported adverse events associated with immune checkpoint modulators.","authors":"Kimberly A Webster,&nbsp;Mary L O'Connor,&nbsp;Aaron R Hansen,&nbsp;Sheetal Kircher,&nbsp;Heather S L Jim,&nbsp;Adam P Dicker,&nbsp;Monika Janda,&nbsp;Kari Ala-Leppilampi,&nbsp;Clifton O Bingham,&nbsp;Josephine Feliciano,&nbsp;Norah Lynn Henry,&nbsp;Laurie E Steffen McLouth,&nbsp;David Cella","doi":"10.20517/2394-4722.2019.38","DOIUrl":"https://doi.org/10.20517/2394-4722.2019.38","url":null,"abstract":"<p><strong>Aim: </strong>To develop a comprehensive item library of patient-reported, immunotherapy-related adverse events (irAEs) that draws from and expands on the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System.</p><p><strong>Methods: </strong>Literature review and iterative expert input. Based on a literature review of irAEs, we developed a framework of immunotherapy classes and their associated symptoms. Clinical experts then reviewed iterations of symptom summaries and item maps linked to the immunotherapy framework. Experts provided content review and feedback was shared across experts until consensus was reached. The iterative process facilitated creation of a Primary Symptom List associated with immune checkpoint modulators (ICMs), drawn from the larger set of symptoms. Existing FACIT items were mapped to the symptom list, and new items were written as needed to create the item library.</p><p><strong>Results: </strong>The full item library of irAEs is comprised of 239 items, covering 142 unique symptoms across 75 inflammatory reactions/immune conditions. A subset of 66 items comprises a Primary Symptom List considered most common/relevant to ICM treatment. This includes gastrointestinal, skin, pulmonary, neurologic, musculoskeletal, and multiple miscellaneous and constitutional symptoms.</p><p><strong>Conclusion: </strong>The FACIT Immunotherapy Item Library is a compilation of 239 self-report items that capture the wide range of AEs experienced by people receiving immune treatments. A subset of 66 items comprises a Primary Symptom List meant for ICM therapy. Use of items selected from this library is encouraged in clinical research and clinical practice evaluation.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39633870","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":"RANBP9 as potential therapeutic target in non-small cell lung cancer.","authors":"Anna Tessari,&nbsp;Shimaa H A Soliman,&nbsp;Arturo Orlacchio,&nbsp;Marina Capece,&nbsp;Joseph M Amann,&nbsp;Rosa Visone,&nbsp;David P Carbone,&nbsp;Dario Palmieri,&nbsp;Vincenzo Coppola","doi":"10.20517/2394-4722.2020.32","DOIUrl":"https://doi.org/10.20517/2394-4722.2020.32","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths in the Western world. Despite progress made with targeted therapies and immune checkpoint inhibitors, the vast majority of patients have to undergo chemotherapy with platinum-based drugs. To increase efficacy and reduce potential side effects, a more comprehensive understanding of the mechanisms of the DNA damage response (DDR) is required. We have shown that overexpressby live cell imaging (Incuyion of the scaffold protein RAN binding protein 9 (RANBP9) is pervasive in NSCLC. More importantly, patients with higher levels of RANBP9 exhibit a worse outcome from treatment with platinum-based drugs. Mechanistically, RANBP9 exists as a target and an enabler of the ataxia telangiectasia mutated (ATM) kinase signaling. Indeed, the depletion of RANBP9 in NSCLC cells abates ATM activation and its downstream targets such as pby live cell imaging (Incuy53 signaling. RANBP9 knockout cells are more sensitive than controls to the inhibition of the ataxia and telangiectasia-related (ATR) kinase but not to ATM inhibition. The absence of RANBP9 renders cells more sensitive to drugs inhibiting the Poly(ADP-ribose)-Polymerase (PARP) resulting in a \"BRCAness-like\" phenotype. In summary, as a result of increased sensitivity to DNA damaging drugs conferred by its ablation <i>in vitro</i> and <i>in vivo</i>, RANBP9 may be considered as a potential target for the treatment of NSCLC. This article aims to report the results from past and ongoing investigations focused on the role of RANBP9 in the response to DNA damage, particularly in the context of NSCLC. This review concludes with future directions and speculative remarks which will need to be addressed in the coming years.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39713189","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":"Exploiting the relevance of CA 19-9 in pancreatic cancer.","authors":"Syaza Salleh,&nbsp;Anita Thyagarajan,&nbsp;Ravi P Sahu","doi":"10.20517/2394-4722.2020.70","DOIUrl":"https://doi.org/10.20517/2394-4722.2020.70","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth most common cause of cancer-related deaths in the United States. It has a poor prognosis and remains a difficulty to treat malignancy. Over the past several decades, significant efforts have been directed towards developing new approaches to enhance the efficacy of therapeutic regimens for PDAC treatment. In recent years, the measurement of serum carbohydrate antigen 19-9 (CA 19-9) has become one of the most validated and extensively used tumour biomarkers for PDAC. In particular, serum CA 19-9 levels have been explored as a validated tool to predict either the signs of disease progression or the response to treatment. However, despite its clinical relevance, the implications on diagnosis or accurately predicting tumour resectability, and monitoring disease symptoms in PDAC patients remains limited. This current review highlights the recent updates on the applicability of CA 19-9, its exploitation, and challenges in predicting the treatment efficacy and responses in PDAC patients.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10566512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41202006","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":"Targeting the JAK/STAT pathway in solid tumors.","authors":"Zoya Qureshy, Daniel E Johnson, Jennifer R Grandis","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Aberrant activation of signal transducer and activator of transcription (STAT) proteins is associated with the development and progression of solid tumors. However, as transcription factors, these proteins are difficult to target directly. In this review, we summarize the role of targeting Janus kinases (JAKs), upstream activators of STATs, as a strategy for decreasing STAT activation in solid tumors. Preclinical studies in solid tumor cell line models show that JAK inhibitors decrease STAT activation, cell proliferation, and cell survival; in <i>in vivo</i> models, they also inhibit tumor growth. JAK inhibitors, particularly the JAK1/2 inhibitor ruxolitinib, sensitize cell lines and murine models to chemotherapy, immunotherapy, and oncolytic viral therapy. Ten JAK inhibitors have been or are actively being tested in clinical trials as monotherapy or in combination with other agents in patients with solid tumors; two of these inhibitors are already Food and Drug Administration (FDA) approved for the treatment of myeloproliferative disorders and rheumatoid arthritis, making them attractive agents for use in patients with solid tumors as they are known to be well-tolerated. Four JAK inhibitors (two of which are FDA approved for other indications) have exhibited promising anti-cancer effects in preclinical studies; however, clinical studies specifically assessing their activity against the JAK/STAT pathway in solid tumors have not yet been conducted. In summary, JAK inhibition is a viable option for targeting the JAK/STAT pathway in solid tumors and merits further testing in clinical trials.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25316997","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":"Deubiquitination in prostate cancer progression: role of USP22.","authors":"Nivedita Nag,&nbsp;Samikshan Dutta","doi":"10.20517/2394-4722.2020.23","DOIUrl":"https://doi.org/10.20517/2394-4722.2020.23","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the leading cause of cancer death in men. With more therapeutic modalities available, the overall survival in PCa has increased significantly in recent years. Patients with relapses after advanced secondgeneration anti-androgen therapy however, often show poor disease prognosis. This group of patients often die from cancer-related complicacies. Multiple approaches have been taken to understand disease recurrence and to correlate the gene expression profile. In one such study, an 11-gene signature was identified to be associated with PCa recurrence and poor survival. Amongst them, a specific deubiquitinase called ubiquitin-specific peptidase 22 (USP22) was selectively and progressively overexpressed with PCa progression. Subsequently, it was shown to regulate androgen receptors and Myc, the two most important regulators of PCa progression. Furthermore, USP22 has been shown to be associated with the development of therapy resistant PCa. Inhibiting USP22 was also found to be therapeutically advantageous, especially in clinically challenging and advanced PCa. This review provides an update of USP22 related functions and challenges associated with PCa research and explains why targeting this axis is beneficial for PCa relapse cases.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39527181","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":"Introduction to this special issue \"Breast Cancer Metastasis\".","authors":"William P Schiemann","doi":"10.20517/2394-4722.2020.01","DOIUrl":"https://doi.org/10.20517/2394-4722.2020.01","url":null,"abstract":"Breast cancer remains the most common malignancy and most frequent cause of cancerrelated death in women, a devasting reality that annually claims more than 600,000 lives across the globe[1]. The vast majority of deaths due to breast cancer are attributed to metastasis and its associated relapse[2,3], which typically transpires in patients ~5-20 years after their initial diagnosis[4]. Although metastasis is the most lethal characteristic of breast cancer, our understanding of the molecular mechanisms that govern this event remains incomplete, a stark reality reinforced by the finding that diagnosis of distant-stage disease has remained unchanged over the course of the last two decades[5].","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 3","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39198145","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}