Journal of Cancer Metastasis and Treatment最新文献

{"title":"Introduction to this Special Issue: \"Biomarker Discovery and Precision Medicine\".","authors":"Bingliang Fang","doi":"10.20517/2394-4722.2019.42","DOIUrl":"https://doi.org/10.20517/2394-4722.2019.42","url":null,"abstract":"With advances in genomics, transcriptomics, proteomics, and metabolomics, blooming data have been available for exploring molecular alternations in cancers. Many of these molecular alternations have been investigated as biomarkers for cancer diagnosis, prognosis, and precision therapies. It is my privilege to introduce this Special Issue of the Journal of Cancer Metastasis and Treatment, which contains four review articles and four original articles that focus on the topic of biomarker discoveries for cancer diagnosis and precision therapy.","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/PMC8589333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39624642","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":"Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance.","authors":"Ahmad R Safa","doi":"10.20517/2394-4722.2020.55","DOIUrl":"10.20517/2394-4722.2020.55","url":null,"abstract":"<p><p>Metastasis, tumor progression, and chemoresistance are the major causes of death in patients with pancreatic ductal adenocarcinoma (PDAC). Tumor dissemination is associated with the activation of an epithelial-to-mesenchymal transition (EMT) process, a program by which epithelial cells lose their cell polarity and cell-to-cell adhesion, and acquire migratory and invasive abilities to become mesenchymal stem cells (MSC). These MSCs are multipotent stromal cells capable of differentiating into various cell types and trigger the phenotypic transition from an epithelial to a mesenchymal state. Therefore, EMT promotes migration and survival during cancer metastasis and confers stemness features to particular subsets of cells. Furthermore, a major problem limiting our ability to treat PDAC is the existence of rare populations of pancreatic cancer stem cells (PCSCs) or cancer-initiating cells in pancreatic tumors. PCSCs may represent sub-populations of tumor cells resistant to therapy which are most crucial for driving invasive tumor growth. These cells are capable of regenerating the cellular heterogeneity associated with the primary tumor when xenografted into mice. Therefore, the presence of PCSCs has prognostic relevance and influences the therapeutic response of tumors. PCSCs express markers of cancer stem cells (CSCs) including CD24, CD133, CD44, and epithelial specific antigen as well as the drug transporter ABCG2 grow as spheroids in a defined growth medium. A major difficulty in studying tumor cell dissemination and metastasis has been the identification of markers that distinguish metastatic cancer cells from cells that are normally circulating in the bloodstream or at sites where these cells metastasize. Evidence highlights a linkage between CSC and EMT. In this review, The current understanding of the PCSCs, signaling pathways regulating these cells, PDAC heterogeneity, EMT mechanism, and links between EMT and metastasis in PCSCs are summarised. This information may provide potential therapeutic strategies to prevent EMT and trigger CSC growth inhibition and cell death.</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/PMC8623975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39927121","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":"Mouse tumor susceptibility genes identify drug combinations for multiple myeloma.","authors":"Shuling Zhang, Wendy DuBois, Ke Zhang, John K Simmons, V Keith Hughitt, Sayeh Gorjifard, Snehal Gaikwad, Tyler J Peat, Beverly A Mock","doi":"10.20517/2394-4722.2020.40","DOIUrl":"10.20517/2394-4722.2020.40","url":null,"abstract":"<p><p>Long-term genetic studies utilizing backcross and congenic strain analyses coupled with positional cloning strategies and functional studies identified <i>Cdkn2a</i>, <i>Mtor</i>, and <i>Mndal</i> as mouse plasmacytoma susceptibility/resistance genes. Tumor incidence data in congenic strains carrying the resistance alleles of <i>Cdkn2a</i> and <i>Mtor</i> led us to hypothesize that drug combinations affecting these pathways are likely to have an additive, if not synergistic effect in inhibiting tumor cell growth. Traditional and novel systems-level genomic approaches were used to assess combination activity, disease specificity, and clinical potential of a drug combination involving rapamycin/everolimus, an <i>Mtor</i> inhibitor, with entinostat, an histone deacetylase inhibitor. The combination synergistically repressed oncogenic <i>MYC</i> and activated the <i>Cdkn2a</i> tumor suppressor. The identification of <i>MYC</i> as a primary upstream regulator led to the identification of small molecule binders of the G-quadruplex structure that forms in the NHEIII region of the <i>MYC</i> promoter. These studies highlight the importance of identifying drug combinations which simultaneously upregulate tumor suppressors and downregulate oncogenes.</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/PMC7486007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38377188","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":"A new view of the mammary epithelial hierarchy and its implications for breast cancer initiation and metastasis.","authors":"Lindsey J Anstine,&nbsp;Ruth Keri","doi":"10.20517/2394-4722.2019.24","DOIUrl":"https://doi.org/10.20517/2394-4722.2019.24","url":null,"abstract":"<p><p>The existence of mammary epithelial stem cell (MaSC) populations capable of mediating mammary gland development and homeostasis has been established for over a decade. A combination of lineage tracing and mammary gland transplantation studies has affirmed that MaSCs and their downstream progenitors are organized in a hierarchal manner; however, these techniques have failed to illuminate the complete spectrum of epithelial intermediate populations or their spatial and temporal relationships. The advent of single cell sequencing technology has allowed for characterization of highly heterogeneous tissues at high resolution. In the last two years, the remarkable advances in single cell RNA sequencing (scRNA-seq) technologies have been leveraged to address the heterogeneity of the mammary epithelium. These studies have afforded fresh insights into the transcriptional differentiation hierarchy and its chronology. Importantly, these data have led to a major conceptual shift in which the rigid boundaries separating stem, progenitor, and differentiated epithelial populations have been deconstructed, resulting in a new more fluid and flexible model of epithelial differentiation. The emerging view of the mammary epithelial hierarchy has important implications for mammary development, carcinogenesis, and metastasis, providing novel insights into the underlying cellular states that may promote malignant phenotypes.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"5 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213536/pdf/nihms-1578731.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37925289","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":"Histone Chaperone FACT and Curaxins: Effects on Genome Structure and Function.","authors":"Han-Wen Chang, Ekaterina V Nizovtseva, Sergey V Razin, Tim Formosa, Katerina V Gurova, Vasily M Studitsky","doi":"10.20517/2394-4722.2019.31","DOIUrl":"10.20517/2394-4722.2019.31","url":null,"abstract":"<p><p>The histone chaperone FACT plays important roles in essentially every chromatin-associated process and is an important indirect target of the curaxin class of anti-cancer drugs. Curaxins are aromatiс compounds that intercalate into DNA and can trap FACT in bulk chromatin, thus interfering with its distribution and its functions in cancer cells. Recent studies have provided mechanistic insight into how FACT and curaxins cooperate to promote unfolding of nucleosomes and chromatin fibers, resulting in genome-wide disruption of contact chromatin domain boundaries, perturbation of higher order chromatin organization, and global disregulation of gene expression. Here, we discuss the implications of these insights for cancer biology.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"5 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919649/pdf/nihms-1062752.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37471513","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":"Cellular plasticity and metastasis in breast cancer: a pre- and post-malignant problem.","authors":"Jacob M Smigiel, Sarah E Taylor, Benjamin L Bryson, Ilaria Tamagno, Kelsey Polak, Mark W Jackson","doi":"10.20517/2394-4722.2019.26","DOIUrl":"10.20517/2394-4722.2019.26","url":null,"abstract":"<p><p>As a field we have made tremendous strides in treating breast cancer, with a decline in the past 30 years of overall breast cancer mortality. However, this progress is met with little affect once the disease spreads beyond the primary site. With a 5-year survival rate of 22%, 10-year of 13%, for those patients with metastatic breast cancer (mBC), our ability to effectively treat wide spread disease is minimal. A major contributing factor to this ineffectiveness is the complex make-up, or heterogeneity, of the primary site. Within a primary tumor, secreted factors, malignant and pre-malignant epithelial cells, immune cells, stromal fibroblasts and many others all reside alongside each other creating a dynamic environment contributing to metastasis. Furthermore, heterogeneity contributes to our lack of understanding regarding the cells' remarkable ability to undergo epithelial/non-cancer stem cell (CSC) to mesenchymal/CSC (E-M/CSC) plasticity. The enhanced invasion & motility, tumor-initiating potential, and acquired therapeutic resistance which accompanies E-M/CSC plasticity implicates a significant role in metastasis. While most work trying to understand E-M/CSC plasticity has been done on malignant cells, recent evidence is emerging concerning the ability for pre-malignant cells to undergo E-M/CSC plasticity and contribute to the metastatic process. Here we will discuss the importance of E-M/CSC plasticity within malignant and pre-malignant populations of the tumor. Moreover, we will discuss how one may potentially target these populations, ultimately disrupting the metastatic cascade and increasing patient survival for those with mBC.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"5 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37891097","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":"Studies of postpartum mammary gland involution reveal novel pro-metastatic mechanisms.","authors":"Taylor R Wallace,&nbsp;Sarah E Tarullo,&nbsp;Lyndsey S Crump,&nbsp;Traci R Lyons","doi":"10.20517/2394-4722.2019.01","DOIUrl":"https://doi.org/10.20517/2394-4722.2019.01","url":null,"abstract":"<p><p>Postpartum involution is the process by which the lactating mammary gland returns to the pre-pregnant state after weaning. Expression of tumor-promotional collagen, upregulation of matrix metalloproteinases, infiltration of M2 macrophages, and remodeling of blood and lymphatic vasculature are all characteristics shared by the involuting mammary gland and breast tumor microenvironment. The tumor promotional nature of the involuting mammary gland is perhaps best evidenced by cases of postpartum breast cancer (PPBC), or those cases diagnosed within 10 years of most recent childbirth. Women with PPBC experience more aggressive disease and higher risk of metastasis than nulliparous patients and those diagnosed outside the postpartum window. Semaphorin 7a (SEMA7A), cyclooxygenase-2 (COX-2), and collagen are all expressed in the involuting mammary gland and, together, predict for decreased metastasis free survival in breast cancer. Studies investigating the role of these proteins in involution have been important for understanding their contributions to PPBC. Postpartum involution thus represents a valuable model for the identification of novel molecular drivers of PPBC and classical cancer hallmarks. In this review, we will highlight the similarities between involution and cancer in the mammary gland, and further define the contribution of SEMA7A/COX-2/collagen interplay to postpartum involution and breast tumor progression and metastasis.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"5 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37035681","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":"Novel Immunotherapeutic Approaches in Head and Neck Cancer.","authors":"M E Heft Neal,&nbsp;C T Haring,&nbsp;J E Mann,&nbsp;J C Brenner,&nbsp;M E Spector,&nbsp;P L Swiecicki","doi":"10.20517/2394-4722.2019.32","DOIUrl":"https://doi.org/10.20517/2394-4722.2019.32","url":null,"abstract":"<p><p>Unresectable recurrent or metastatic head and neck cancer is an incurable disease with survival of approximately 12 months. Head and neck tumors exhibit numerous derangements in the tumor microenvironment that aid in immune evasion and may serve as targets for future therapies. Pembrolizumab is now approved as a first line therapy. Despite the promise of currently approved immunotherapies there continues to be low response rates and additional strategies are needed. Here, alterations in the immune microenvironment and current therapeutic strategies are reviewed with a focus on novel immunologic approaches.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"5 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357897/pdf/nihms-1564902.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38156685","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":"A non-toxic approach for treatment of breast cancer and its metastases: capecitabine enhanced photodynamic therapy in a murine breast tumor model.","authors":"Sanjay Anand, Anton Yasinchak, Taylor Bullock, Mukul Govande, Edward V Maytin","doi":"10.20517/2394-4722.2018.98","DOIUrl":"10.20517/2394-4722.2018.98","url":null,"abstract":"<p><strong>Aim: </strong>Breast cancer (BCA) in women is a leading cause of mortality and morbidity; distant metastases occur in ~40% of cases. Here, as an alternative to ionizing radiation therapy and chemotherapy and their associated side effects, we explored a new combination approach using capecitabine (CPBN) and aminolevulinate-based photodynamic therapy (PDT). We had previously developed a combination PDT approach in which 5-fluorouracil (5FU), a differentiation-promoting agent, increases the levels of protoporphyrin IX (PpIX) in cancer cells when given as a neoadjuvant prior to aminolevulinic acid (ALA). However, 5FU can be toxic when administered systemically at high levels. We reasoned that CPBN, a known chemotherapeutic for BCA and less toxic than 5FU (because CPBN is metabolized to 5FU specifically within tumor tissues), might work equally well as a PDT neoadjuvant.</p><p><strong>Methods: </strong>Murine 4T1 BCA cells harboring a luciferase transgene were injected into breast fat pads of female nude mice. CPBN (600 mg/kg/day) was administered by oral gavage for 3 days followed by intraperitoneal ALA administration and PDT with red light (633 nm) on day 4. Tumor growth and regression were monitored <i>in vivo</i> using bioluminescence imaging. Histological changes in primary tumors and metastases were assessed by immunohistochemistry after necropsy.</p><p><strong>Results: </strong>CPBN pretreatment of 4T1 tumors increased cellular differentiation, reduced proliferation, raised PpIX levels, enhanced tumor cell death, and reduced metastatic spread of 4T1 cells post-PDT, relative to vehicle-only controls.</p><p><strong>Conclusion: </strong>The use of CPBN as a non-toxic PDT neoadjuvant for treatment of BCA represents a novel approach with significant potential for translation into the clinic.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"5 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36947286","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":"Metabolic alterations and the potential for targeting metabolic pathways in the treatment of multiple myeloma.","authors":"Dustin Rizzieri, Barry Paul, Yubin Kang","doi":"10.20517/2394-4722.2019.05","DOIUrl":"10.20517/2394-4722.2019.05","url":null,"abstract":"<p><p>Metabolism is defined as the collection of complex biochemical processes that living cells use to generate energy and maintain their growth and survival. Metabolism encompasses the synthesis and breakdown of glucose, fatty acids, and amino acids; the generation of energy (ATP); and oxidative phosphorylation. In cancer cells, metabolism can be commandeered to promote tumor growth and cellular proliferation. These alterations in metabolism have emerged as an additional hallmark of various cancers. In this review we focus on metabolic alterations in multiple myeloma (MM) - a malignancy of plasma cells - including derangements in glycolysis, gluconeogenesis, the tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid/amino acid synthesis and degradation. Particular focus is given to metabolic alterations that contribute to myeloma cell growth, proliferation and drug resistance. Finally, novel approaches that target metabolic pathways for the treatment of MM are discussed.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"5 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37180971","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}