Oncoscience最新文献

{"title":"EGFR mutations in sinonasal squamous tumors: oncogenic and therapeutic implications","authors":"A. Udager, J. Mchugh, K. Elenitoba-Johnson, N. Brown","doi":"10.18632/ONCOSCIENCE.268","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.268","url":null,"abstract":"Sinonasal squamous cell carcinoma (SNSCC) and sinonasal papillomas constitute a diverse group of epithelial tumors arising in the sinonasal tract [1]. Sinonasal papillomas are benign tumors classified into three distinct histologic types: exophytic (fungiform), inverted, and oncocytic. While exophytic sinonasal papillomas (ESP) arise from the nasal septum and are only rarely associated with SNSCC, inverted sinonasal papillomas (ISP) and oncocytic sinonasal papillomas (OSP) typically arise from the lateral portion of the nasal cavity and are more frequently associated with synchronous or metachronous SNSCC – up to 25%, depending on the study [2]. \u0000 \u0000The etiology of sinonasal tumors is a topic of current debate [1]. While ESP is associated with infection by low-risk human papillomavirus (HPV) in 55% - 65% [1, 3], most studies have demonstrated significantly lower HPV detections rates for ISP [3, 4]. Similarly, less than half of SNSCC are associated with HPV infection [3, 4] and the incidence in SNSCC associated with ISP may be even lower [5]. These data suggest that while HPV infection may play a role in the pathogenesis of a subset of these tumors, it is not the only factor involved in SNP and SNSCC oncogenesis. \u0000 \u0000In a recent study, our group identified activating somatic EGFR mutations in 88% of ISP and 77% of SNSCC associated with ISP [6]. Importantly, while a variety of different EGFR mutations were found in these tumors, concordant EGFR genotypes were identified for all matched pairs of ISP and synchronous or metachronous SNSCC. Therefore, this study provided the first molecular evidence to support the role of ISP as a precursor lesion for SNSCC. In addition, EGFR mutation status was a significant prognostic factor for ISP, with EGFR wild-type tumors showing earlier progression to SNSCC. No EGFR mutations were identified in ESP, OSP, or SNSCC not associated with ISP, suggesting that the ISP/SNSCC disease spectrum is biologically distinct from these other sinonasal squamous tumors. \u0000 \u0000The oncogenic role of EGFR mutations was supported in this study by functional experiments. In cell lines derived from ISP-associated SNSCC, EGFR mutations were shown to result in activation of EGFR as well as downstream constituents of the MAPK and PI3K/AKT/mTOR signaling pathways. Taken together, these functional studies and the high frequency of EGFR mutations suggest that dysregulated EGFR signaling plays a central role in the oncogenesis of ISP and associated SNSCC – a finding that is an apparent departure from prior paradigms involving HPV infection [1]. These findings, however, do not strictly preclude a role for HPV in these tumors. The HPV-associated E5 oncoprotein has been shown to inhibit EGFR degradation, alter endosomal trafficking of EGFR and activate proteins downstream of EGFR in a ligand-independent manner [7] (Figure ​(Figure1).1). Thus, it is plausible that altered EGFR signaling itself – either as a result of somatic activating EGFR mutations ","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"7 1","pages":"908 - 909"},"PeriodicalIF":0.0,"publicationDate":"2015-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78435473","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}

{"title":"An added dimension to tumour TRAIL sensitivity","authors":"Sandra Healy, L. O’Leary, E. Szegezdi","doi":"10.18632/ONCOSCIENCE.267","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.267","url":null,"abstract":"Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF cytokine family and a selective inducer of apoptosis in a range of tumour cells, but not in healthy normal, untransformed cells. It is expressed by natural killer cells and natural killer-T cells when they encounter malignantly transformed cells and it is a key effector molecule in tumour immune surveillance. TRAIL has 5 receptors, which is the highest receptor promiscuity in the TNF ligand family. It binds to death receptor 4 (DR4) or DR5 on the surface of target cells [1] and initiates a conformational change which promotes association of the receptors with FADD facilitating pro-caspase-8 and/or pro-caspase-10 recruitment which then activates effector caspases to execute cell death [2]. Signalling through DR4 and DR5 can also activate pro-inflammatory intracellular molecules such as MAPK, PKB and NF-κB and overexpression of DR4 or DR5 has been shown to stimulate the release of inflammatory cytokines [3]. However, TRAIL also has three regulatory receptors. Two of these, decoy receptor 1(DcR1) and DcR2 are membrane bound and the third regulatory receptor, osteoprotegerin is a secreted protein. DcRs regulate TRAIL-induced apoptosis by either sequestering TRAIL from the death receptors or by forming inactive, heteromeric DcR1/2–DR4/5 complexes [1]. Indeed, DcRs have been shown to be highly expressed in a number of tumour tissues such as acute myeloid leukaemia, prostate cancer and breast cancer and their expression is linked with poor prognosis [4]. However DcR expression in tumour cells does not correlate with TRAIL sensitivity and non-transformed cells do not require DcRs to be protected from TRAIL-induced apoptosis, suggesting that the in vivo role of the DcRs may be more complex than originally thought [5] \u0000 \u0000The tumor-specific cytotoxicity of TRAIL has been exploited as a therapeutic strategy by utilizing recombinant versions of TRAIL and agonistic antibodies against DR4 and DR5 [6]. While recombinant soluble human TRAIL was highly potent against a broad range of tumours in vitro and in pre-clinical studies, in clinical trials TRAIL has failed to exhibit the same potency [6]. One of the major shortcomings of the preclinical models was the lack of assessment of the contribution of the tumour microenvironment (TME). The TME consists of various cell types, soluble factors and signals from the extracellular matrix, and is in a reciprocal interaction with the tumour cells. It is thus important to understand the interplay of different cell types in the tumour microenvironment and the effect of the factors they express and secrete on tumour growth, development and resistance to therapy. \u0000 \u0000 \u0000 \u0000Figure 1 \u0000 \u0000Cell autonomous and supracellular regulation of TRAIL-sensitivity by decoy receptor 1 (DcR1) and -2 \u0000 \u0000 \u0000 \u0000The study by O'Leary and colleagues explored the hypothesis that DcRs exerted a ‘supracellular level control’ of TRAIL-sensitivity rather than simply regula","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"9 1","pages":"906 - 907"},"PeriodicalIF":0.0,"publicationDate":"2015-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88893847","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}

{"title":"Runx1: a new driver in neurofibromagenesis","authors":"Jianqiang Wu, Gang Huang, N. Ratner","doi":"10.18632/ONCOSCIENCE.266","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.266","url":null,"abstract":"The Runt-related transcription factor-1 (RUNX1 or AML1) encodes a transcription factor that serves as a master developmental regulator. It is important for hematopoiesis, angiogenesis, maturation of megakaryocytes, and differentiation of T and B cells [1]. Runx1 is also important for neuronal development and glial cell differentiation [2]. Runx1 is integrated into a complex regulatory network which acts both at the transcriptional and post-transcriptional levels. Runx1 activity can be regulated by several posttranslational modifications, including phosphorylation, de-phosphorylation, SUMOylation, acetylation, methylation and ubiquitination. These modifications control various aspects of transcriptional factors' activities such as auto inhibition, dimerization and ubiquitin-mediated degradation [3]. \u0000 \u0000Besides its developmental determination role, RUNX1 is involved in malignant tumor formation. Reports have shown that RUNX1 is frequently de-regulated and has paradoxical effects in human cancers, in which it can function either as a tumor suppressor or oncogene [3, 4]. RUNX1 has been implicated as a tumor suppressor in several solid tumors including breast cancer, esophageal adenocarcinoma, colon cancer and possibly prostate cancer but acts as an oncogene in head/neck squamous cell carcinomas, endometrial cancer, and epithelial cancer [3, 4]. Because Runx1 is a sequence specific DNA-binding transcription factor, whether it functions as oncogene or tumor suppressor is dependent on its interaction with specific co-regulatory proteins. \u0000 \u0000We recently showed that RUNX1 acts as an oncogene in the context of loss of neurofibromatosis type 1 (Nf1). Instead of chromosomal translocation and mutation frequently detected in other cancers, Runx1 is overexpressed in human and mouse neurofibroma-initiating cells, both at the messenger RNA and protein levels. Specifically, loss of Nf1 increases number of embryonic day 12.5 Runx1+/Blbp+ Schwann cell progenitors that enable neurofibroma formation in a mouse model (Figure ​(Figure1).1). Targeted genetic deletion of RUNX1 in Schwann cells and Schwann cell progenitors delays mouse neurofibroma formation in vivo (5). \u0000 \u0000 \u0000 \u0000Figure 1 \u0000 \u0000Model of neurofibromagenesis \u0000 \u0000 \u0000 \u0000It is not clear how loss of Nf1 induces Runx1 overexpression and serves as an oncogene. There are several potential possibilities: 1) NF1 is known to encode a Ras-GTPase activating protein (Ras-GAP) and the Ras-MEK-ERK pathway is important for Nf1 neurofibroma formation [6]. Runx1 may be phosphorylated by the elevated MEK signaling to initiate the tumor formation process. 2) Elevated Wnt or Notch signaling can directly or indirectly activate Runx1, which can accelerate G1-S transition and stimulates cell proliferation. Consistently, our results show that loss of Runx1 in Schwann cells decreased cell proliferation by activating Trp53-p21 or increased cell apoptosis by inhibiting anti-apoptotic gene Bcl-2 in the context of Nf1−/− Schwann cell environment","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"379 1","pages":"904 - 905"},"PeriodicalIF":0.0,"publicationDate":"2015-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76614638","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}

{"title":"Kinetochore-microtube attachments in cancer therapy","authors":"D. Del Bufalo, F. Degrassi","doi":"10.18632/ONCOSCIENCE.265","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.265","url":null,"abstract":"The process of cell division represents an extraordinary target to develop antitumor therapies. Indeed, a large number of clinically relevant anti-cancer drugs, such as taxanes and vinca alkaloids, target mitosis by stimulating or inhibiting microtubule (MT) polymerization. During the past decades anti-tubulin drugs have proven very effective against a wide range of tumors. However, collateral effects, such as myelosuppression and MT disruption in non-dividing tissues, including brain, are common. Recently, the increased understanding of the cell division process and the identification of several signaling pathways controlling mitosis have provided novel opportunities for cancer drug discovery. Consequently, mitotic proteins have become attractive targets to develop molecular cancer therapeutics. In this scenario, kinetochores (KTs) represent an attractive therapeutic target in light of their fundamental role in driving chromosome segregation and controlling chromosome segregation errors. Indeed, cells require a fine regulation of the kinetochore-microtubule (KT-MT) attachment stability to prevent chromosome instability, and KT-MT attachment dynamics is often deregulated in tumour cells [2]. Chromosome instability is commonly accepted as a driving force in the development of cancer, but more recent work has demonstrated that extensive chromosome missegregation may be detrimental to cancer cells and act as a tumor suppression mechanism [3]. In light of this double role of chromosome instability in cancer, we have explored the hypothesis that interfering with KT-MT attachment dynamics could drive massive chromosome missegregation and kill tumor cells. Highly Expressed in Cancer protein 1 (Hec1) is a constituent of the evolutionary conserved Ndc80 complex, the molecular connector between KTs and MTs. Among the subunits of the Ndc80 complex, Hec1 directly interacts with MTs and regulates KT-MT dynamics and attachment stability [3]. Importantly, Hec1 is frequently overexpressed in cancer. We previously demonstrated that expression of Hec1 fused with the enhanced green fluorescent protein (EGFP) tag at its N-terminus (EGFP-Hec1), the protein domain that regulates MT attachment dynamics, led to a strong accumulation of this modified protein, which acted as a dominant negative mutant over the endogenous Hec1. Mitotic cells expressing a N-terminus tagged Hec1 accumulated lateral KT-MT attachments and underwent a spindle assembly checkpoint (SAC) dependent mitotic arrest associated with the formation of multipolar spindles [4]. We further showed that expression of an inducible N-terminus modified Hec1 completely abolished in vitro growth of EGFP-Hec1 expressing HeLa cells but had no effects on untransformed human fibroblasts or epithelial cells [5]. These in vitro cell-based data were validated in vivo by showing that inducible EGFP-Hec1 expression strongly inhibited tumor growth in a HeLa xenograft mouse model [5]. Strikingly, in both in vitro and in vivo","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"43 1","pages":"902 - 903"},"PeriodicalIF":0.0,"publicationDate":"2015-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82653381","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}

{"title":"Snail1 controls cooperative cell plasticity during metastasis","authors":"J. Baulida","doi":"10.18632/ONCOSCIENCE.262","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.262","url":null,"abstract":"Mortality in cancer is strongly associated with the capacity of tumor cells to spread and critically affect other tissues and organs. Genetic mutations accumulated by tumor cells and cross-signaling between tumor and host cells underlie the formation of metastasis. Cancer-activated fibroblasts (CAFs), which are host fibroblasts activated by tumor signaling, can alter tumor cell behavior by both paracrine signaling (secreting diffusible molecules) and mechanical signaling (modifying the composition and organization of the stroma). These fibroblasts resemble myofibroblasts (MFs) of the granulation tissue generated during wound healing, which produce a rigid desmoplastic stroma rich in signaling molecules and cross-linked extracellular fibers. Desmoplasia favors malignant tumor cell properties such as mobility, stemness, and even resistance to pharmacological insults [1].","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"33 1","pages":"898 - 899"},"PeriodicalIF":0.0,"publicationDate":"2015-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73297482","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}

{"title":"NETosis in cancer","authors":"J. Cedervall, A. Olsson","doi":"10.18632/ONCOSCIENCE.264","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.264","url":null,"abstract":"A large proportion of cancer-related deaths are caused by thrombosis and general organ failure. Although the awareness of tumor-induced systemic effects has increased significantly in recent years, current knowledge is still mainly restricted to metastatic sites. Surprisingly little is known about the situation in organs that are not targets for metastasis or directly affected by the primary tumor. We therefore decided to look deeper into this relatively unexplored field of cancer research. For obvious reasons human biopsy material from tissues not affected by tumor cells, in an individual with cancer, are rare and mouse models therefore become important tools for such investigations. Using two different orthotopic and spontaneously metastasizing tumor models - the RIP1-Tag2 model for insulinoma with metastasis to the liver and the MMTV-PyMT model for mammary carcinoma with lung metastasis - we analyzed the presence of hematopoietic cells in organs which do not represent sites for primary tumor growth. There was a significant increase in the number of neutrophils in heart and kidneys of tumor-bearing mice compared to healthy individuals [1]. In mice with cancer, peripheral organs displayed systemic inflammation and impaired vascular function, which was restored upon neutrophil depletion. Platelet/neutrophil complexes, indicative of neutrophil extracellular traps (NETs), were found in kidney and heart from tumor-bearing mice, while these complexes were completely absent in the corresponding tissues from healthy mice. Indeed, analysis of peripheral blood confirmed the presence of neutrophils with extracellular DNA-tails in tumor-bearing mice.","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"4 1","pages":"900 - 901"},"PeriodicalIF":0.0,"publicationDate":"2015-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90189648","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}

{"title":"A pivotal role for HOXB7 protein in endocrine resistant breast cancer","authors":"Kideok Jin, S. Sukumar","doi":"10.18632/ONCOSCIENCE.263","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.263","url":null,"abstract":"HOXB7 is a homeodomain containing transcription factor which plays a pivotal role in tamoxifen resistant breast cancer. Our work has shown that overexpression of HOXB7 renders cells tamoxifen resistant by mobilizing a number of receptor tyrosine kinase pathways. EGFR expression is upregulated by direct binding of HOXB7 to the EGFR promoter, while HOXB7 functions as a cofactor with ERα to cause overexpression of multiple ER-target genes, including HER2, in tamoxifen resistant breast cancer cells. Probing the pathway further, we found that miR-196a and MYC are upstream regulators of HOXB7 expression. Mechanistically, HOXB7 and ERα jointly upregulate HER2 which phosphorylates MYC. Thus stabilized, MYC in turn suppresses miR-196a. Loss of miR-196a results lifts the quelling influence of miR-196a on HOXB7 expression. Besides shedding light on the intricate interplay of events occurring in tamoxifen resistant breast cancer, the work identifies a number of new therapeutic targets capable of restoring sensitivity of breast cancer cells to tamoxifen.","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"1 1","pages":"917 - 919"},"PeriodicalIF":0.0,"publicationDate":"2015-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89546764","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}

{"title":"New alternative splicing BCR/ABL-OOF shows an oncogenic role by lack of inhibition of BCR GTPase activity and an increased of persistence of Rac activation in chronic myeloid leukemia","authors":"C. Panuzzo, G. Volpe, E. C. Rocchietti, C. Casnici, K. Crotta, S. Crivellaro, Giovanna Carrá, Roberta Lorenzatti, Barbara Peracino, Davide Torti, A. Morotti, M. P. Camacho-Leal, P. Defilippi, O. Marelli, G. Saglio","doi":"10.18632/ONCOSCIENCE.260","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.260","url":null,"abstract":"In Chronic Myeloid Leukemia 80% of patients present alternative splice variants involving BCR exons 1, 13 or 14 and ABL exon 4, with a consequent impairment in the reading frame of the ABL gene. Therefore BCR/ABL fusion proteins (BCR/ABL-OOF) are characterized by an in-frame BCR portion followed by an amino acids sequence arising from the out of frame (OOF) reading of the ABL gene. The product of this new transcript contains the characteristic BCR domains while lacking the COOH-terminal Rho GTPase GAP domain. The present work aims to characterize the protein functionality in terms of cytoskeleton (re-)modelling, adhesion and activation of canonical oncogenic signalling pathways. Here, we show that BCR/ABL-OOF has a peculiar endosomal localization which affects EGF receptor activation and turnover. Moreover, we demonstrate that BCR/ABL-OOF expression leads to aberrant cellular adhesion due to the activation of Rac GTPase, increase in cellular proliferation, migration and survival. When overexpressed in a BCR/ABL positive cell line, BCR/ABL-OOF induces hyperactivation of Rac signaling axis offering a therapeutic window for Rac-targeted therapy. Our data support a critical role of BCR/ABL-OOF in leukemogenesis and identify a subset of patients that may benefit from Rac-targeted therapies.","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"124 1","pages":"880 - 891"},"PeriodicalIF":0.0,"publicationDate":"2015-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76223000","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}

{"title":"A ceRNA approach may unveil unexpected contributors to deletion syndromes, the model of 5q- syndrome","authors":"W. Arancio, S. Genovese, L. Bongiovanni, C. Tripodo","doi":"10.18632/ONCOSCIENCE.261","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.261","url":null,"abstract":"In genomic deletions, gene haploinsufficiency might directly configure a specific disease phenotype. Nevertheless, in some cases no functional association can be identified between haploinsufficient genes and the deletion-associated phenotype. Transcripts can act as microRNA sponges. The reduction of transcripts from the hemizygous region may increase the availability of specific microRNAs, which in turn may exert in-trans regulation of target genes outside the deleted region, eventually contributing to the phenotype. Here we prospect a competing endogenous RNA (ceRNA) approach for the identification of candidate genes target of epigenetic regulation in deletion syndromes. As a model, we analyzed the 5q- myelodysplastic syndrome. Genes in haploinsufficiency within the common 5q deleted region in CD34+ blasts were identified in silico. Using the miRWalk 2.0 platform, we predicted microRNAs whose availability, and thus activity, could be enhanced by the deletion, and performed a genomewide analysis of the genes outside the 5q deleted region that could be targeted by the predicted miRNAs. The analysis pointed to two genes with altered expression in 5q- transcriptome, which have never been related with 5q- before. The prospected approach allows investigating the global transcriptional effect of genomic deletions, possibly prompting discovery of unsuspected contributors in the deletion-associated phenotype. Moreover, it may help in functionally characterizing previously reported unexpected interactions.","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"129 1","pages":"872 - 879"},"PeriodicalIF":0.0,"publicationDate":"2015-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76938055","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}

{"title":"Selective amino acid restriction therapy (SAART): a non-pharmacological strategy against all types of cancer cells","authors":"M. López-Lázaro","doi":"10.18632/ONCOSCIENCE.258","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.258","url":null,"abstract":"Metastasis will continue to be an incurable disease for most patients until we develop highly selective anticancer therapies. The development of these therapies requires finding and exploiting major differences between cancer cells and normal cells. Although the sum of the many DNA alterations of cancer cells makes up such a major difference, there is currently no way of exploiting these alterations as a whole. Here I propose a non-pharmacological strategy to selectively kill any type of cancer cell, including cancer stem cells, by exploiting their complete set of DNA alterations. It is based on creating challenging environmental conditions that only cells with undamaged DNAs can overcome. Cell survival requires continuous protein synthesis, which in turn requires adequate levels of 20 amino acids (AAs). If we temporarily restrict specific AAs and keep high levels of others whose deficit triggers proteolysis, we will force cells to activate a variety of genetic programs to obtain adequate levels of each of the 20 proteinogenic AAs. Because cancer cells have an extremely altered DNA that has evolved under particular environmental conditions, they may be unable to activate the genetic programs required to adapt to and survive the new environment. Cancer patients may be successfully treated with a protein-free artificial diet in which the levels of specific AAs are manipulated. Practical considerations for testing and implementing this cheap and universal anticancer strategy are discussed.","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"33 1","pages":"857 - 866"},"PeriodicalIF":0.0,"publicationDate":"2015-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86821104","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}