Oncoscience最新文献

{"title":"Association between tumor mutations and meningioma recurrence in Grade I/II disease.","authors":"Jonathan T Dullea,&nbsp;Vikram Vasan,&nbsp;John W Rutland,&nbsp;Corey M Gill,&nbsp;Danielle Chaluts,&nbsp;Daniel Ranti,&nbsp;Ethan Ellis,&nbsp;Varun Subramanium,&nbsp;Annie Arrighi-Allisan,&nbsp;Yayoi Kinoshita,&nbsp;Russell B McBride,&nbsp;Joshua Bederson,&nbsp;Michael Donovan,&nbsp;Robert Sebra,&nbsp;Melissa Umphlett,&nbsp;Raj K Shrivastava","doi":"10.18632/oncoscience.570","DOIUrl":"https://doi.org/10.18632/oncoscience.570","url":null,"abstract":"<p><strong>Background: </strong>Meningiomas are common intracranial tumors with variable prognoses not entirely captured by commonly used classification schemes. We sought to determine the relationship between meningioma mutations and oncologic outcomes using a targeted next-generation sequencing panel.</p><p><strong>Materials and methods: </strong>We identified 184 grade I and II meningiomas with both >90 days of post-surgical follow-up and linked targeted next-generation sequencing. For mutated genes in greater than 5% of the sample, we computed progression-free survival Cox-regression models stratified by gene. We then built a multi-gene model by including all gene predictors with a <i>p</i>-value of less than 0.20. Starting with that model, we performed backward selection to identify the most predictive factors.</p><p><strong>Results: </strong><i>ATM</i> (HR = 4.448; 95% CI: 1.517-13.046), <i>CREBBP</i> (HR = 2.727; 95% CI = 1.163-6.396), and <i>POLE</i> (HR = 0.544; HR = 0.311-0.952) were significantly associated with alterations in disease progression after adjusting for clinical and pathologic factors. In the multi-gene model, only POLE remained a significant predictor of recurrence after adjusting for the same clinical covariates. Backwards selection identified recurrence status, resection extent, and mutations in <i>ATM</i> (HR = 7.333; 95% CI = 2.318-23.195) and <i>POLE</i> (HR = 0.413; 95% CI = 0.229-0.743) as predictive of recurrence.</p><p><strong>Conclusions: </strong>Mutations in ATM and CREBBP were associated with accelerated meningioma recurrence, and mutations in POLE were protective of recurrence. Each mutation has potential implications for treatment. The effect of these mutations on oncologic outcomes and as potential targets for intervention warrants future study.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":"9 ","pages":"70-81"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9733702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10353899","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":"Potential roles of <i>FAT1</i> somatic mutation in progression of head and neck cancer.","authors":"Zhuo G Chen,&nbsp;Yong Teng","doi":"10.18632/oncoscience.558","DOIUrl":"https://doi.org/10.18632/oncoscience.558","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide [1]. It disturbs patients’ vital upper aero-digestive function. Treatment outcomes for patients with HNSCC remain poor in past decades due to the lack of effective therapeutic options, thereby, discovery and evaluation of new medications are of tremendous importance for improving patients’ survival. Human papillomavirus (HPV) status remains one of strong indicators of survival, however, HPV-unrelated disease carrying a 5-year overall survival (OS) rate of less than 50% [2]. The challenges in effectively treating HNSCC are attributed to its extreme heterogeneity as far as anatomic locations and genetic aberrations. Major gaps in understanding the biology of disease continue to be the main reason behind the paucity of effective therapeutic interventions. FAT1 encodes a member of the cadherin-like protein family. Under normal physiological conditions, FAT1 serves as a molecular “brake” on mitochondrial respiration [3] and acts as a receptor for a signaling pathway regulating cell-cell contact interaction and planar cell polarity [4, 5]. Loss of fat leads to cell cycle dysregulation and hyperproliferation in Drosophila larval imaginal discs [6]. Recently, FAT1 mutations were identified in human cancers and may contribute to Wnt activation, suggesting that FAT1 may serve as a tumor suppressor in human cells [7]. The FAT1 mutant was found to inactivate the Hippo regulatory complex, which leads to activation of YAP1 in HNSCC as reported by Martin et al. They also indicated that the FAT1 gene alteration rate was as high as 29.8% in HNSCC, which is the highest among solid tumors [8]. FAT1 mutation was reported to be more common in HPV-negative (HPV−) than in HPV-positive (HPV+) HNSCC (28% vs. 2.8%). Mann et al., examined 16 HNSCC cell lines and reported a FAT1 mutation rate of 43% [9]. One recent study on Research Perspective","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":"9 ","pages":"30-32"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10598660","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":"VTT-006, an anti-mitotic compound, binds to the Ndc80 complex and suppresses cancer cell growth <i>in vitro</i>.","authors":"Leena J Laine,&nbsp;Jenni H E Mäki-Jouppila,&nbsp;Emma Kutvonen,&nbsp;Pekka Tiikkainen,&nbsp;Thomas K M Nyholm,&nbsp;Jerry F Tien,&nbsp;Neil T Umbreit,&nbsp;Ville Härmä,&nbsp;Lila Kallio,&nbsp;Trisha N Davis,&nbsp;Charles L Asbury,&nbsp;Antti Poso,&nbsp;Gary J Gorbsky,&nbsp;Marko J Kallio","doi":"10.18632/oncoscience.549","DOIUrl":"https://doi.org/10.18632/oncoscience.549","url":null,"abstract":"<p><p>Hec1 (Highly expressed in cancer 1) resides in the outer kinetochore where it works to facilitate proper kinetochore-microtubule interactions during mitosis. Hec1 is overexpressed in various cancers and its expression shows correlation with high tumour grade and poor patient prognosis. Chemical perturbation of Hec1 is anticipated to impair kinetochore-microtubule binding, activate the spindle assembly checkpoint (spindle checkpoint) and thereby suppress cell proliferation. In this study, we performed high-throughput screen to identify novel small molecules that target the Hec1 calponin homology domain (CHD), which is needed for normal microtubule attachments. 4 million compounds were first virtually fitted against the CHD, and the best hit molecules were evaluated <i>in vitro</i>. These approaches led to the identification of VTT-006, a 1,2-disubstituted-tetrahydro-beta-carboline derivative, which showed binding to recombinant Ndc80 complex and modulated Hec1 association with microtubules <i>in vitro</i>. VTT-006 treatment resulted in chromosome congression defects, reduced chromosome oscillations and induced loss of inter-kinetochore tension. Cells remained arrested in mitosis with an active spindle checkpoint for several hours before undergoing cell death. VTT-006 suppressed the growth of several cancer cell lines and enhanced the sensitivity of HeLa cells to Taxol. Our findings propose that VTT-006 is a potential anti-mitotic compound that disrupts M phase, impairs kinetochore-microtubule interactions, and activates the spindle checkpoint.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":"8 ","pages":"134-153"},"PeriodicalIF":0.0,"publicationDate":"2021-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39852982","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":"Berry anthocyanidins inhibit intestinal polyps and colon tumors by modulation of Src, EGFR and the colon inflammatory environment.","authors":"Ashley M Mudd,&nbsp;Tao Gu,&nbsp;Radha Munagala,&nbsp;Jeyaprakash Jeyabalan,&nbsp;Mostafa Fraig,&nbsp;Nejat K Egilmez,&nbsp;Ramesh C Gupta","doi":"10.18632/oncoscience.548","DOIUrl":"https://doi.org/10.18632/oncoscience.548","url":null,"abstract":"<p><p>Colorectal cancer is the third most common form of cancer diagnosed and the third leading class for cancer-related deaths. Given the prevalence of colon cancer worldwide, further insight into developing novel and effective prevention and treatment strategies are warranted. The family of plant pigments known as the anthocyanins has been identified with a variety of health benefits including chemopreventive and therapeutic effects. A limitation to current clinical applications of anthocyanins is the high doses that are required. In order to overcome this limitation, we tested the active moiety, anthocyanidins for chemopreventive and therapeutic effects against colorectal cancer <i>in vivo</i> and <i>in vitro</i>. Treatment with native anthocyanidin mixture (Anthos) from bilberry yielded significant antiproliferative activity against colon cancer cells. Anthos treatment led to significant reductions in polyp and tumor counts <i>in vivo</i>. Reduced Src and EGFR phosphorylation was observed with Anthos treatment, which correlated with downstream targets such as PD-L1 and modulation of the colon inflammatory environment. These results provide a promising outlook on the impact of berry Anthos for the treatment and prevention of familial adenomatous polyposis and colorectal cancer. Results from this study also provide novel mechanistic insight into the chemopreventive and therapeutic activities of Anthos.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":"8 ","pages":"120-133"},"PeriodicalIF":0.0,"publicationDate":"2021-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39852528","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":"Correction: Targeting focal adhesion kinase overcomes erlotinib resistance in smoke induced lung cancer by altering phosphorylation of epidermal growth factor receptor.","authors":"Hitendra S Solanki,&nbsp;Remya Raja,&nbsp;Alex Zhavoronkov,&nbsp;Ivan V Ozerov,&nbsp;Artem V Artemov,&nbsp;Jayshree Advani,&nbsp;Aneesha Radhakrishnan,&nbsp;Niraj Babu,&nbsp;Vinuth N Puttamallesh,&nbsp;Nazia Syed,&nbsp;Vishalakshi Nanjappa,&nbsp;Tejaswini Subbannayya,&nbsp;Nandini A Sahasrabuddhe,&nbsp;Arun H Patil,&nbsp;T S Keshava Prasad,&nbsp;Daria Gaykalova,&nbsp;Xiaofei Chang,&nbsp;Rachana Sathyendran,&nbsp;Premendu Prakash Mathur,&nbsp;Annapoorni Rangarajan,&nbsp;David Sidransky,&nbsp;Akhilesh Pandey,&nbsp;Evgeny Izumchenko,&nbsp;Harsha Gowda,&nbsp;Aditi Chatterjee","doi":"10.18632/oncoscience.546","DOIUrl":"https://doi.org/10.18632/oncoscience.546","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.18632/oncoscience.395.].</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":"8 ","pages":"108-109"},"PeriodicalIF":0.0,"publicationDate":"2021-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39494816","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":"The hyperfunction theory of aging: three common misconceptions.","authors":"Mikhail V Blagosklonny","doi":"10.18632/oncoscience.545","DOIUrl":"10.18632/oncoscience.545","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":"8 ","pages":"103-107"},"PeriodicalIF":0.0,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39438365","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":"Tune the channel: TRPM8 targeting in prostate cancer.","authors":"Alessandro Alaimo,&nbsp;Dario De Felice,&nbsp;Sacha Genovesi,&nbsp;Marco Lorenzoni,&nbsp;Andrea Lunardi","doi":"10.18632/oncoscience.543","DOIUrl":"https://doi.org/10.18632/oncoscience.543","url":null,"abstract":"<p><p>The therapeutic landscape of cancer treatments is quickly evolving thanks to the advent of precision oncology. Discovery of novel druggable targets and more reliable biomarkers is a primary objective towards personalized strategies of cancer treatment. Highly expressed in the prostate epithelium within the human body, Transient Receptor Potential subfamily M member 8 (TRPM8) levels rise in primary and hormone naïve metastatic prostate cancer (PCa) lesions, which makes this channel an interesting prototype of molecular target. Recently, by combining a multidisciplinary approach to an <i>in vitro</i> genetic platform, we demonstrated that the combination of potent TRPM8 agonists with X-rays induces a massive apoptotic response in radioresistant pre-malignant and malignant models of primary prostate lesions. As well, TRPM8 activation enhances the efficacy of docetaxel or enzalutamide in eradicating hormone naïve metastatic PCa cells. Overall, our findings provide a solid rationale for pursuing the pre-clinical and clinical study of TRPM8 as a valuable target for future approaches of precise oncology in PCa.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":"8 ","pages":"97-100"},"PeriodicalIF":0.0,"publicationDate":"2021-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39412577","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":"Determining the utility of a screening program to reduce the incidence of HPV driven oropharyngeal cancer.","authors":"Sarju Vasani,&nbsp;Ian Frazer,&nbsp;Chamindie Punyadeera","doi":"10.18632/oncoscience.541","DOIUrl":"https://doi.org/10.18632/oncoscience.541","url":null,"abstract":"<p><p>The last decade has seen a continued escalation in rates of human papillomavirus related oropharyngeal malignancy (HPV-OPC). This has occurred despite established national vaccination programs. In contrast, HPV associated cervical cancer incidence rates have declined, due in part to effective cervical cancer screening programs, many of which have moved towards the detection of high-risk HPV (hrHPV) as an early marker of malignant potential. This raises questions as to whether similar hrHPV screening methods could be used for early detection of HPV-OPC. Persistent oral hrHPV is a prerequisite for the development of HPV-OPC and can be accurately detected in saliva. Despite this, single point saliva testing for hrHPV lacks sufficient sensitivity and specificity to allow for effective population screening. Recent published literature suggests the use of serial saliva testing in targeted high-risk individuals, with an emphasis on biomarker persistence and intensity patterns, as a potential means of detecting even subclinical microscopic disease. When coupled with serological testing, this has the potential to provide an accurate test for screening at risk individuals. Despite these promising developments, several significant barriers to an effective targeted screening program remain.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":"8 ","pages":"91-93"},"PeriodicalIF":0.0,"publicationDate":"2021-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39306765","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":"Re-enforcing the strategy of targeting MEK/ERK signaling to overcome acquired resistance to third generation EGFR inhibitors.","authors":"Wen Zhao,&nbsp;Shi-Yong Sun","doi":"10.18632/oncoscience.539","DOIUrl":"https://doi.org/10.18632/oncoscience.539","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":"8 ","pages":"80-81"},"PeriodicalIF":0.0,"publicationDate":"2021-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39301446","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 precision approach to breast cancer treatment based on cell lineage-specific vulnerabilities.","authors":"Jay S Desgrosellier","doi":"10.18632/oncoscience.538","DOIUrl":"https://doi.org/10.18632/oncoscience.538","url":null,"abstract":"Breast cancers display significant intra-tumoral heterogeneity posing a major barrier to effective breast cancer treatments [1, 2]. This heterogeneity can be manifested in terms of genetic abnormalities or the presence of distinct cell types bearing similarities to the different epithelial lineages in the normal adult mammary gland including: luminal cells, basal cells, their respective progenitors, and stem cells [3]. The cell lineages present within a given tumor may determine the likelihood of progression. This is best exemplified by sub-populations of tumor-initiating cells present in aggressive breast cancers, some of which resemble adult mammary stem cells [4-9] and thus are termed stem-like. These stem-like cells are enriched in residual tumors after chemotherapy [10] as well as early metastatic lesions [11], suggesting they play a critical role in breast cancer progression. While attempts to treat breast cancers based on genetic mutations have largely been unsuccessful, therapies targeting particular cell lineages, including stem-like cells, are gaining renewed appreciation. Toward this goal, studies have uncovered distinct dependencies among different breast cancer cell types for particular cell death/survival pathways. These recent advances may open the door for new highly personalized approaches to breast cancer therapy. Our previous studies found that stem-like cells were highly sensitive to cell death induced by p53-upregulated mediator of apoptosis (PUMA) [12], a pro-apoptotic BH3-only member of the Bcl-2 family. These effects were specific to PUMA [12] as the related family member NOXA had no effect on stem-like cells consistent with its role in targeting basal-like breast cancer cells [13]. We further found that driving PUMA expression was sufficient to deplete stem-like cells and reduce metastasis in vivo, revealing its role as an important metastasis suppressor. Our results are consistent with published findings that PUMA-mediated cell death is the preferred response in some normal adult stem cell populations [14]. In an effort Research Perspective","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":"8 ","pages":"76-79"},"PeriodicalIF":0.0,"publicationDate":"2021-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39092409","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}