Purpose:Here, we report results of the first phase I study of erdafitinib, a potent, oral pan-FGFR inhibitor. Patients and Methods:Patients age ≥18 years with advanced solid tumors for which standard antineoplastic therapy was no longer effective were enrolled (NCT01703481). Parts 2 to 4 employed molecular screening for activating FGFR genomic alterations. In patients with such alterations, two selected doses/schedules identified during part 1 dose-escalation [9 mg once daily and 10 mg intermittently...
Metastatic non–small-cell lung cancer is still a devastating disease; however, treatment options have diversified dramatically in the past two decades. From unselected platinum-based chemotherapy for all patients, several different treatment groups have evolved, that is, those with "druggable" targets, those with a promising immune signature, and those without any predicting factors outlined in this article. Challenge includes the intersections between these groups and the optimal treatment path....
Gynecologic malignancies continue to be a major cause of morbidity and mortality in the United States despite recent advances in oncologic therapies. To realize the promise of immunotherapy and biomarker-driven approaches to improve clinical outcomes for patients, better communication among stakeholders in the drug development and approval pathways is needed. To this end, the FDA-AACR-SGO Drug Development in Gynecologic Malignancies Workshop brought together clinicians, patient advocates, researchers,...
Induction of antitumor responses by vaccines requires strong immunogens. Heterologous viral prime/boost immunization with the BN-CV301 vaccine promotes activation of immune responses that provide a clinical benefit to patients with cancer. This viral platform may be used to harbor different antigens and prime tumor immunity potentially useful for combinatorial strategies. See related article by Gatti-Mays et al., p. 4933
The positive but limited efficacy of JAK inhibitors has sparked the need for alternative therapeutic targets in the treatment of myelofibrosis. The discovery of novel targets, like Aurora Kinase A, may provide new avenues of single-agent and combinatorial therapy for myelofibrosis and restoration of normal bone marrow function. See related article by Gangat et al., p. 4898
Fusions between NRG1 and partner genes are rare, tumorigenic genomic events occurring in patients with lung and other cancers, associated with activation of ERBB2/ERBB3 heterodimers. Inhibition of ERBB2 and/or ERBB3 in this group of patients is a promising strategy in clinical trials. See related article by Jonna et al., p. 4966
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In Saccharomyces cerevisiae more than 250 trans-acting factors are involved in the maturation of 40S and 60S ribosomal subunits. The expression of most of these factors is transcriptionally co-regulated to ensure correct ribosome production under a wide variety of environmental and intracellular conditions. Here, we identified the essential nucleolar Pol5 protein as a novel trans-acting factor required for the synthesis of 60S ribosomal subunits. Pol5 weakly and/or transiently associates with early...
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Tubeimoside-I (TBM), a plant-derived bioactive compound, shows antitumor activity in different tumors and can enhance the efficacy of chemotherapeutic agents. However, the detail mechanism underlying remains t...
Human epidermal growth factor receptor 2 (HER2) is overexpressed in multiple cancers, which is associated with poor prognosis. Herceptin and other agents targeting HER2 have potent antitumor efficacy in patien...
Long noncoding RNAs (lncRNAs) have been reported to be associated with the proliferation of several cancer cells. The aim of this study was to investigate the role of FLVCR1-AS1 in ovarian serous cancer (OSC).
Estrogen receptor β (ERβ) has been reported to play an anti-cancer role in breast cancer, but the regulatory mechanism by which ERβ exerts this effect is not clear. Claudin-6 (CLDN6), a tight junction protein,...
In the original publication of this article [1], the author’ affiliations need to be revised, because the first and second affiliations should combine as the same affiliation.
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Abstract A non‐targeted plasma metabolomic analysis was conducted to compare differentially expressed metabolites in women with and without fibromyalgia (FM) using data and samples collected from two parent studies in women with fibromyalgia (n=20) and comparative data collected from newly recruited age‐matched women (n=20). Blood plasma samples were analyzed for metabolite content using liquid chromatography mass spectrometry. Consolidation of positive and negative ion mode metabolomics data with...
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ABSTRACT We report an Xp11 translocation PEComa with a novel RBMX‐TFE3 gene fusion, resulting from a paracentric X chromosome inversion, inv(X)(p11;q26). The neoplasm occurred in an otherwise healthy 12‐year‐old male who presented with a large left renal mass with extension into the inferior vena cava. The patient was found to have multiple pulmonary metastases at diagnosis and died of disease 3 months later. The morphology (epithelioid clear cells with alveolar and nested architecture) and immunophenotype...
ABSTRACT Hypoxia‐induced epithelial‐mesenchymal transition (EMT) involves the interplay between chromatin modifiers histone deacetylase 3 (HDAC3) and WDR5. The histone mark acetylation of histone 3 lysine 4 (H3K4Ac) is observed in the promoter regions of various EMT marker genes (eg, CDH1, VIM). To further define the genome‐wide location of H3K4Ac, a chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP‐seq) analysis was performed using a head and neck squamous cell carcinoma...
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Publication date: September 2019Source: European Journal of Cancer, Volume 119Author(s): Roman C. Maron, Michael Weichenthal, Jochen S. Utikal, Achim Hekler, Carola Berking, Axel Hauschild, Alexander H. Enk, Sebastian Haferkamp, Joachim Klode, Dirk Schadendorf, Philipp Jansen, Tim Holland-Letz, Bastian Schilling, Christof von Kalle, Stefan Fröhling, Maria R. Gaiser, Daniela Hartmann, Anja Gesierich, Katharina C. Kähler, Ulrike WehkampAbstractBackgroundRecently, convolutional neural networks (CNNs)...
Publication date: September 2019Source: European Journal of Cancer, Volume 119Author(s): Anne Zaremba, Rajmohan Murali, Philipp Jansen, Inga Möller, Antje Sucker, Annette Paschen, Lisa Zimmer, Elisabeth Livingstone, Titus J. Brinker, Eva Hadaschik, Cindy Franklin, Alexander Roesch, Selma Ugurel, Dirk Schadendorf, Klaus G. Griewank, Ioana CosgareaAbstractStudy aimMelanomas arising in acral sites are associated with a poorer prognosis than other melanoma subtypes. The aim of this study was to evaluate...
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Future Oncology, Ahead of Print.
Future Oncology, Ahead of Print.
Future Oncology, Ahead of Print.
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Publication date: Available online 14 August 2019Source: Critical Reviews in Oncology/HematologyAuthor(s): Irina Tsibulak, Alain G. Zeimet, Christian MarthAbstractThrough the last three decades, the combination of paclitaxel and carboplatin remains the standard of care chemotherapy in newly diagnosed epithelial ovarian cancer (EOC). Based on a single trial, first-line maintenance therapy with angiogenesis inhibitor bevacizumab was approved in Europe and widely applied. In 2018, based on a second...
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Abstract Objectives Many countries are implementing human papillomavirus (HPV)‐based cervical screening due to the higher sensitivity of the test compared with cytology. As HPV is sexually transmitted, there may be psychosexual consequences of testing positive for the virus. We aimed to review the literature exploring the psychosexual impact of testing positive for high‐risk cervical HPV. Methods MEDLINE, PsycINFO, CINAHL Plus, Web of Science and EMBASE were searched with no date limits....
Abstract Objective Seasonal effects on patients diagnosed with depression/anxiety‐related psychological disorders have varying impacts on symptom severity. Seasonal changes in psychological distress may be due to decreased daylight exposure during the fall/winter seasons. Patients receiving radiation therapy (RT) for early‐stage invasive breast cancer (EIBC) are at high risk for developing depressive symptoms. Of interest is whether seasonal factors influence the psychological symptoms of patients...
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Purpose: MET deregulated NSCLC represents an urgent clinical need because of unfavorable prognosis and lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET amplification or exon 14 mutations, no conclusivedata are currently available. The present study aimed at investigating activity of crizotinib in patients harboring MET or ROS1 alterations. Experimental Design: Patients with pretreated advanced NSCLC and evidence of ROS1rearrangements...
Tumours evolve in close interaction with their microenvironment, which encompasses a continual tension between the developing tumour and the host immune system. Clinical trials have shown that appropriate enhancement of a tumour immune response can lead to long-lasting clinical responses and patient benefit. Understanding the contribution of the immune contexture, in addition to the molecular subtype across different tumour indications, is a significant knowledge gap with limited sagacity to drive...
Purpose: Preclinical and retrospective studies suggested a role for metformin in sensitizing diabetic non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs). We therefore examined its effects in combination with gefitinib in non-diabetic patients harboring EGFR mutations (EGFRm). Experimental design: 224 non-diabetic patients with treatment naïve stage IIIB-IV EGFRm NSCLC were randomly assigned in a 1:1 ratio to receive gefitinib plus...
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Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC), with local control rates of 80% or less at 5 years. Given the unsatisfactory outcomes for these patients, there is a clear need for intensification of local therapy, including radiation. Inhibition of the DNA repair protein poly adenosine diphosphate-ribose polymerase 1 (PARP1) has had little efficacy as a single agent in breast cancer outside of studies restricted to patients with...
Cancer immunotherapy is a promising new approach to cancer treatment. It has been demonstrated that a high number of tumor-specific cytotoxic T cells (CTLs) is associated with increased survival in multiple myeloma (MM) patients. Here, we focused on Epidermal growth factor receptor pathway substrate 8 (Eps8) as a candidate tumor-associated antigen (TAA) in MM. Previous work has shown that Eps8-based immunotherapy in HLA-A2+ cancer patients may result in efficient antitumor immune responses against...
Bladder cancer is the ninth most common cause of cancer-related deaths worldwide. Although cisplatin is used routinely in treating bladder cancer, refractory disease remains lethal for many patients. The recent addition of immunotherapy has improved patient outcomes, however a large cohort of patients do not respond to these treatments. Therefore, identification of innovative molecular targets for bladder cancer is crucial. Apurinic/apyrimidinic endonuclease 1/ redox factor-1 (APE1/Ref-1) is a multifunctional...
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At present, the standard treatment approach for locally advanced cervical cancer is concurrent chemoradiotherapy (CCRT). An elevated pretreatment squamous cell carcinoma antigen (SCC Ag) level is associated wi...
Heterogeneous target doses are a common by-product from attempts to improve normal tissue sparing in radiosurgery treatment planning. These regions of escalated dose within the target may increase tumor contro...
Despite the success of fractionation in clinical practice to spare healthy tissue, it remains common for mouse models used to study the efficacy of radiation therapy to use minimal or no fractionation. The goa...
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Related ArticlesManagement of one patient with oligoprogressive thyroid cancer during treatment with lenvatinib. Future Oncol. 2019 Aug 14;: Authors: Porcelli T, Sessa F, Gambale C, Luongo C, Salvatore D Abstract Recent thyroid cancer guidelines found it reasonable to use local therapies during treatment with tyrosine kinase inhibitors (TKIs) in selected patients with oligoprogressive disease, namely, in the presence of a single progressing lesion in...
Related ArticlesNatural killer cells: a Review of biology, therapeutic potential and challenges in treatment of solid tumors. Future Oncol. 2019 Aug 14;: Authors: Choucair K, Duff JR, Cassidy CS, Albrethsen MT, Kelso JD, Lenhard A, Staats H, Patel R, Brunicardi FC, Dworkin L, Nemunaitis J Abstract Natural killer (NK) cells lead immune surveillance against cancer and early elimination of small tumors. Owing to their ability to engage tumor targets without...
Related ArticlesThe 1-year mortality after radiotherapy for nasopharyngeal carcinoma: a population-based analysis. Future Oncol. 2019 Aug 14;: Authors: Wu SG, Zhang WW, Wang J, Lian CL, He ZY, Rong YM, Lin Q Abstract Aim: To assess the incidence and predictors of nasopharyngeal carcinoma (NPC)-specific mortality in the first year among NPC patients. Methods: We identified 2714 patients in the SEER program. Results: Of the patients, 151 (5.6%) patients...
Fruquintinib and its use in the treatment of metastatic colorectal cancer. Future Oncol. 2019 Aug 13;: Authors: Deng Y, Li X Abstract Fruquintinib is a potent, highly selective and orally active inhibitor of VEGFR1, 2, 3 tyrosine kinases. It inhibits VEGF-induced VEGFR2 phosphorylation, endothelial cell proliferation and tubule formation. Currently, it has been approved for the treatment of metastatic colorectal cancer in patients who have failed at...
Related ArticlesDacomitinib in non-small-cell lung cancer: a comprehensive review for clinical application. Future Oncol. 2019 Aug 12;: Authors: Sun H, Wu Y Abstract Dacomitinib is a second-generation EGFR tyrosine kinase inhibitor (TKI) that irreversibly binds to and inhibits EGFR/Her1, Her2 and Her4 subtypes with an efficacy comparable to other TKIs. In the ARCHER 1050 trial, progression-free survival was improved by dacomitinib compared with gefitinib,...
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Abstract Although CAR T-cell therapy has demonstrated tremendous clinical efficacy especially in hematological malignancies, severe treatment-associated toxicities still compromise the widespread application of this innovative technology. Therefore, developing novel approaches to abrogate CAR T-cell-mediated side effects is of great relevance. Several promising strategies pursue the selective antibody-based depletion of adoptively transferred T cells via elimination markers. However,...
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Abstract To establish the more relevant questions oncologic patients may have during cancer treatment. Cross-sectional observational study with all patients undergoing chemotherapy or radiotherapy for cancer in a Brazilian health institution. A questionnaire with open and close questions about cancer diagnosis, treatment, and prognosis was applied. A total of 198 patients were evaluated of whom 122 (62%) were female and 80% of the patients were between 50 and 89 years old. Sixty-one...
Abstract Students have become more familiar with cancer because of media, such as television or the Internet, reporting on celebrity cancer cases. Moreover, with Japan’s increasing age and cancer rates, the number of students whose parents/relatives develop cancer is likely to increase. This study examined cancer awareness and understanding among students aged 10 to 16 or more. A cross-sectional nationwide survey was conducted using a self-administered questionnaire. Cancer awareness...
Abstract Expanding frontiers of knowledge have prompted medical schools to reconsider how best to promote learning in the face of information overload. Concept mapping (CM) promotes knowledge retention and integration. Students have perceived CM positively in prior studies, but the feasibility and utility of integrating CM into a medical student oncology curriculum as a learning and assessment tool have not been described. At the University of California, San Francisco, 152 medical...
Abstract In general, refugees have an increased cancer burden because of living in difficult conditions and having low income. Refugee women may have difficulty in accessing healthcare services because of the fear of uncertainty, security concerns, language barriers, cultural differences, and economic problems. For this reason, it is thought that health education given to Syrian refugee women by overcoming the language problem (given in their own language—Arabic) increases the...
Abstract Although the Champion’s Health Belief Model Scale for breast cancer screening has been adapted and validated in different populations worldwide, a Spanish version for the Latin American population is still not available. The aim of this study was to adapt and validate the Spanish version of the Champion’s Health Belief Model Scale for mammograms for use with Mexican women and determine the sociodemographic, clinical, and health belief model variables which influence undergoing...
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Background Discrimination and trust are known barriers to accessing health care. Despite well‐documented racial disparities in the ovarian cancer care continuum, the role of these barriers has not been examined. This study evaluated the association of everyday discrimination and trust in physicians with a prolonged interval between symptom onset and ovarian cancer diagnosis (hereafter referred to as prolonged symptom duration). Methods Subjects included cases enrolled in the African American...
Background Cancer cachexia is characterized by weight loss and is associated with increased morbidity and mortality in patients with cancer. Anamorelin (ONO‐7643; ANAM) is a novel and selective ghrelin receptor agonist that improves appetite, lean body mass (LBM), body weight, and anorexia. Methods This multicenter, open‐label, single‐arm study investigated the efficacy and safety of 100 mg anamorelin in 50 Japanese patients with advanced and unresectable gastrointestinal (colorectal, gastric,...
Background Late mortality was investigated in patients with chronic myelogenous leukemia (CML) who underwent blood or bone marrow transplant (BMT) with or without prior tyrosine kinase inhibitor (TKI) therapy. Methods By using data from the Blood or Marrow Transplant Survivor Study, the authors examined late mortality in 447 patients with CML who underwent BMT between 1974 and 2010, conditional on surviving ≥2 years post‐BMT. For vital status information, the medical records, the National...
Background A critical knowledge gap exists regarding the impact of neurologic deficits on surgical outcomes and health‐related quality of life (HRQOL) for patients surgically treated for metastatic epidural spinal cord compression (MESCC). Methods This prospective, multicenter and international study analyzed the impact of the neurologic status on functional status, HRQOL, and postoperative survival. The collected data included the patient demographics, overall survival, American Spinal Injury...
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Publication date: Available online 13 August 2019Source: Seminars in OncologyAuthor(s): Giuseppe Palma, Serena Monti, Manuel Conson, Roberto Pacelli, Laura CellaAbstractMathematical models of normal tissue complication probability (NTCP) able to robustly predict radiation-induced morbidities (RIM) play an essential role in the identification of a personalized optimal plan, and represent the key to maximizing the benefits of technological advances in radiation therapy (RT). Most modern RT techniques...
Publication date: Available online 13 August 2019Source: Seminars in OncologyAuthor(s): Tilmann Rackwitz, Jürgen DebusABSTRACTTreatment of cancer patients with charged particles like proton and carbon ions landmarks a new era in high-precision medicine. This review aims to summarize the physical and biological advantages of charged particle beams over conventional photon irradiation, presents some highlights in the treatment of selected tumor entities, and gives an update on previous and ongoing...
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Abstract Background To evaluate the prognostic role of interleukin-6 (IL-6) in renal cell carcinoma (RCC). Method Relevant research articles were obtained from literature databases. Data were extracted from study reports which reported IL-6 levels in relevance to RCC prognosis and random-effects meta-analyses were performed to estimate IL-6 levels, percentage...
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Publication date: Available online 13 August 2019Source: European Journal of Surgical OncologyAuthor(s): J.M. Simons, A.J.G. Maaskant-Braat, E.J.T. Luiten, M.H. Leidenius, T.J.A. van Nijnatten, P.G. Boelens, L.B. Koppert, C.C. van der Pol, C.J.H. van de Velde, R.A. Audisio, M.L. SmidtAbstractIntroductionVarious options for axillary staging after neoadjuvant systemic therapy (NST) are available for breast cancer patients with a clinically positive axillary node (cN+). This survey assessed current...
Publication date: Available online 13 August 2019Source: European Journal of Surgical OncologyAuthor(s): Carlos A. Garcia-Etienne, Alberta Ferrari, Angelica Della Valle, Marco Lucioni, Elisa Ferraris, Giuseppe Di Giulio, Luigi Squillace, Elisabetta Bonzano, Angioletta Lasagna, Gianpiero Rizzo, Richard Tancredi, Andrea Scotti Foglieni, Francesca Dionigi, Maurizia Grasso, Eloisa Arbustini, Giorgio Cavenaghi, Paolo Pedrazzoli, Andrea R. Filippi, Paolo Dionigi, Adele SgarellaAbstractThe surgical approach...
Publication date: Available online 13 August 2019Source: European Journal of Surgical OncologyAuthor(s): Francois Gouin, Arthur Renault, Axelle Bertrand-Vasseur, Loic Bouilleau, Vincent Crenn, Philippe Rosset, Matthias Tallegas, Rami Samargandi, Louis-Romée Le NailAbstractIntroductionMyxoid Round cell containing myxoid liposarcomas (MRCLS) have a high propensity to metastasize to soft tissue and bone. Whole Body Magnetic Resonance Imaging (BMRI) has been reported as a critical modality to early detect...
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British Journal of Cancer, Published online: 16 August 2019; doi:10.1038/s41416-019-0546-yImpact of depth of response on survival in patients treated with cobimetinib ± vemurafenib: pooled analysis of BRIM-2, BRIM-3, BRIM-7 and coBRIM
British Journal of Cancer, Published online: 16 August 2019; doi:10.1038/s41416-019-0542-2Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer
British Journal of Cancer, Published online: 15 August 2019; doi:10.1038/s41416-019-0551-1Bortezomib administered prior to temozolomide depletes MGMT, chemosensitizes glioblastoma with unmethylated MGMT promoter and prolongs animal survival
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Abstract The plasma membrane (PM) is considered as a major druggable site. More than 50% of the existing drugs target PM proteins. In the wake of emerging data indicating a key role of estrogens in prostate cancer (PCa) pathogenesis, the study was undertaken to explore whether the estrogen binding sites exist on the PM and if such sites are functionally relevant in PCa. Estradiol (E2) binding to the PM was detected in androgen‐dependent (LNCaP), androgen‐independent (PC3, DU145) PCa cell lines,...
Cover Caption: The cover image is based on the In Perspective Targeting ERK beyond the boundaries of the kinase active site in melanoma by Rachel M. Sammons et al., DOI 10.1002/mc.23047.
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Total body irradiation (TBI) has been widely used for conditioning prior to hematopoietic stem cell transplantation (HCT). Dose escalation of TBI produces decreased relapse rates in patients with leukemia [1,2]. However, treatment-related deaths increase because of organ toxicity from TBI [1,2]. This outcome negates any potential advantage for survival with escalated doses of TBI. Recently, total marrow irradiation (TMI) was developed to achieve dose escalation with helical Tomotherapy [3–7] while...
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