International journal of cancer and clinical research最新文献

{"title":"Overcoming Endocrine Resistance in Hormone-Receptor Positive Advanced Breast Cancer-The Emerging Role of CDK4/6 Inhibitors.","authors":"Ciara C O'Sullivan","doi":"10.23937/2378-3419/2/4/1029","DOIUrl":"10.23937/2378-3419/2/4/1029","url":null,"abstract":"<p><p>Dysregulation of the cyclin D and cyclin-dependent kinase (CDK) pathway in cancer cells may inhibit senescence and promote cellular proliferation. By using various different mechanisms, malignant cells may increase cyclin D-dependent activity. The cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway controls the cell cycle restriction point, and is commonly dysregulated in breast cancer; making it a rational target for anticancer therapy. To date, three oral highly selective cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are in various stages of clinical development: PD0332991 (palbociclib), LEE011 (ribociclib) and LY2835219 (abemaciclib). Results from phase I, II and III trials in hormone-receptor (HR)-positive breast cancer have been encouraging, demonstrating convincing efficacy and a tolerable side-effect profile (mainly uncomplicated neutropenia). This article will review the preclinical and clinical development of the CDK4/6i, as well as reviewing the existing preclinical evidence regarding combination of these agents with chemotherapy and other targeted therapies. Future and ongoing clinical trials, which may expand the potential application of these agents, will also be discussed. In summary, CDK4/6i are exciting compounds which may change the therapeutic landscape of HR-positive breast cancer.</p>","PeriodicalId":13873,"journal":{"name":"International journal of cancer and clinical research","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81564601","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":"Gene-Specific Promoter Methylation Status in Hormone-Receptor-Positive Breast Cancer Associates with Postmenopausal Body Size and Recreational Physical Activity.","authors":"Lauren E McCullough,&nbsp;Jia Chen,&nbsp;Alexandra J White,&nbsp;Xinran Xu,&nbsp;Yoon Hee Cho,&nbsp;Patrick T Bradshaw,&nbsp;Sybil M Eng,&nbsp;Susan L Teitelbaum,&nbsp;Mary Beth Terry,&nbsp;Gail Garbowski,&nbsp;Alfred I Neugut,&nbsp;Hanina Hibshoosh,&nbsp;Regina M Santella,&nbsp;Marilie D Gammon","doi":"10.23937/2378-3419/2/1/1013","DOIUrl":"https://doi.org/10.23937/2378-3419/2/1/1013","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer, the leading cancer diagnosis among American women, is positively associated with postmenopausal obesity and little or no recreational physical activity (RPA). However, the underlying mechanisms of these associations remain unresolved. Aberrant changes in DNA methylation may represent an early event in carcinogenesis, but few studies have investigated associations between obesity/RPA and gene methylation, particularly in postmenopausal breast tumors where these lifestyle factors are most relevant.</p><p><strong>Methods: </strong>We used case-case unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between body mass index (BMI=weight [kg]/height [m²]) in the year prior to diagnosis, or RPA (average hours/week), and methylation status (methylated vs. unmethylated) of 13 breast cancer-related genes in 532 postmenopausal breast tumor samples from the Long Island Breast Cancer Study Project. We also explored whether the association between BMI/RPA and estrogen/progesterone-receptor status (ER+PR+ vs. all others) was differential with respect to gene methylation status. Methylation-specific PCR and the MethyLight assay were used to assess gene methylation.</p><p><strong>Results: </strong>BMI 25-29.9kg/m², and perhaps BMI≥30kg/m², was associated with methylated <i>HIN1</i> in breast tumor tissue. Cases with BMI≥30kg/m² were more likely to have ER+PR+ breast tumors in the presence of unmethylated <i>ESR1</i> (OR=2.63, 95% CI 1.32-5.25) and women with high RPA were more likely to have ER+PR+ breast tumors with methylated <i>GSTP1</i> (OR=2.33, 95% CI 0.79-6.84).</p><p><strong>Discussion: </strong>While biologically plausible, our findings that BMI is associated with methylated <i>HIN1</i> and BMI/RPA are associated with ER+PR+ breast tumors in the presence of unmethylated <i>ESR1</i> and methylated <i>GSTP1</i>, respectively, warrant further investigation. Future studies would benefit from enrolling greater numbers of postmenopausal women and examining a larger panel of breast cancer-related genes.</p>","PeriodicalId":13873,"journal":{"name":"International journal of cancer and clinical research","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440485/pdf/nihms-683885.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33332472","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":"Prognostic Significance of Hormone Receptor (ER/PR) Status Inendometrial Carcinoma in Black Women: Implications with Lymph Node Metastasis","authors":"Shah Manan, Oprea Gabriela, Shafia Saba, Surapaneni Phani Keerthi, Sasidharan Sandeep, J. Sanjay","doi":"10.23937/2378-3419/1410150","DOIUrl":"https://doi.org/10.23937/2378-3419/1410150","url":null,"abstract":"","PeriodicalId":13873,"journal":{"name":"International journal of cancer and clinical research","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78827511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}