Background LMB‐100 is an antibody‐toxin conjugate with an antimesothelin Fab linked to a 24‐kilodalton portion of Pseudomonas exotoxin A with mutations that decrease immunogenicity. The objective of the current first‐in‐human phase 1 study was to determine the maximum tolerated dose (MTD) and safety in patients with advanced solid tumors expressing mesothelin. Methods Cohorts of 1 to 7 patients received intravenous LMB‐100 at 7 dose levels from 40 µg/kg to 250 µg/kg intravenously on days 1,...
Tue Sep 01, 2020 17:56
Abstract Objective To assess the prognostic and predictive ability of early C-reactive protein (CRP) kinetics, dynamic changes in CRP levels, in patients with advanced urothelial cancer treated with pembrolizumab. Patients and methods We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab in second-line...
Wed Sep 02, 2020 03:00
Abstract Neoantigens are T-cell antigens derived from protein-coding mutations in tumor cells. Although neoantigens have recently been linked to anti-tumor immunity in long-term survivors of cancers such as melanoma, their prognostic and immune-modulatory role in many cancer types remain unexplored. We investigate neoantigens in hepatocellular carcinoma (HCC) through a combination of whole exome sequencing (WES), RNA sequencing (RNA-seq), computational bioinformation, and immunohistochemistry....
Wed Sep 02, 2020 03:00
Molecular alterations that contribute to long-term (LT) and short-term (ST) survival in ovarian high-grade serous carcinoma (HGSC) may be used as precision medicine biomarkers. DNA promoter methylation is an early event in tumorigenesis, which can be detected in blood and urine, making it a feasible companion biomarker to somatic mutations for early detection and targeted treatment workflows. We compared the methylation profile in 12 HGSC tissue samples to 30 fallopian tube epithelium samples, using...
Wed Sep 02, 2020 10:05
The impact of HER2 status in ductal carcinoma in situ (DCIS) on the risk of progression to invasive ductal carcinoma (IDC) has been debated. We aim to use a national database to identify patients with known HER2 status to elucidate the effect of HER2 overexpression on ipsilateral IDC (iIDC) development. We performed survival analysis on patient-level data using the U.S. NCI's Surveillance Epidemiology and End Results program. We identified patients diagnosed with DCIS who underwent lumpectomy and...
Wed Sep 02, 2020 10:05
Withaferin A (hereafter abbreviated as WA) is a promising anticancer steroidal lactone abundant in a medicinal plant (Withania somnifera) native to Asia. The root/leaf extract of Withania somnifera, which belongs to the Solanaceae family, continues to be included in the Ayurvedic medicine formulations of alternative medicine practice. Numerous chemicals are detectable in the root/leaf extract of Withania somnifera [e.g., withanolides (WA, withanone, withanolide A, etc.), alkaloids, sitoindosides,...
Wed Sep 02, 2020 10:05
Many people are diagnosed with cancer after presenting with signs and symptoms of their disease to a healthcare provider. Research from developed countries suggests that, in addition to indicating later-stage disease, symptoms can also indicate earlier-stage disease, leading to investment in research and quality improvement efforts in the early detection of symptomatic cancers. This approach, labeled early diagnosis of symptomatic cancers, focuses on identifying cancer at the earliest possible stage...
Wed Sep 02, 2020 10:05
The STAT3 pathway is frequently overactive in non–small cell lung cancer (NSCLC), an often fatal disease with known risk factors including tobacco and chemical exposures. Whether STAT3 can be downmodulated to delay or prevent development of lung cancer resulting from an environmental exposure has not been previously tested. A circular oligonucleotide STAT3 decoy (CS3D) was used to treat mice previously exposed to the tobacco carcinogen nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. CS3D...
Wed Sep 02, 2020 10:05
Endoscopic History and Provider Characteristics Influence Gastric Cancer Survival in Asian Americans
Gastric carcinoma (GC) disproportionately affects Asian Americans. We examined whether history of upper gastrointestinal (GI) endoscopy was associated with lower stage at GC diagnosis among Asian Americans and whether origin of providers influenced referral for endoscopy. We employed Surveillance Epidemiology and End Results–Medicare data on Asian Americans diagnosed with GC in 2004–2013 (n = 1,554). Stage distribution, GI conditions at diagnosis, and history of endoscopy were compared between...
Wed Sep 02, 2020 10:05
Psychological stressors have been implicated in the progression of various tumor types. We investigated a role for stress in tumor immune cell chemotaxis in the B16F10 mouse model of malignant melanoma. We exposed female mice to 6-hour periods of restraint stress (RST) for 7 days, then implanted B16F10 malignant melanoma tumor cells and continued the RST paradigm for 14 additional days. We determined serum corticosterone and liver catecholamine concentrations in these mice. To evaluate the tumor...
Wed Sep 02, 2020 10:05
In preclinical studies, celecoxib has been associated with reduced risk of breast cancer. In this study, the aim was to assess the biomodulatory effect of celecoxib on blood and benign breast tissue biomarkers in women at increased risk for breast cancer. Women at increased risk for breast cancer [5-year Gail risk score of >1.67%, history of atypical hyperplasia, lobular carcinoma in situ, or previous estrogen receptor (ER)-negative breast cancer] were treated with celecoxib at 400 mg orally twice...
Wed Sep 02, 2020 10:05
Publication date: Available online 1 September 2020Source: Cancer/RadiothérapieAuthor(s): M. Rogé, S. Thureau, J. Carrilho, J. Thariat, S. Rivera
Wed Sep 02, 2020 14:36
Purpose: Dickkopf-1 (DKK1) modulates Wnt signaling, promoting tumor growth, metastasis, and immunosuppression. High DKK1 expression has been detected in various tumor types-including biliary tract cancer (BTC)-and is associated with poor prognosis. DKN-01-a humanized monoclonal antibody targeting DKK1-was evaluated in a phase I multicenter study in combination with gemcitabine and cisplatin in patients with unresectable or metastatic BTC with no prior systemic therapy for advanced disease. Methods:...
Wed Sep 02, 2020 15:35
Publication date: Available online 1 September 2020Source: Critical Reviews in Oncology/HematologyAuthor(s): Amit Mahipal, Sri Harsha Tella, Anuhya Kommalapati, James Yu, Richard Kim
Wed Sep 02, 2020 15:42
Publication date: Available online 1 September 2020Source: Critical Reviews in Oncology/HematologyAuthor(s): Lauren F. Schuch, Felipe M. Silveira, Vivian P. Wagner, Gabriell B. Borgato, Guilherme Z. Rocha, Rogerio M. Castilho, Pablo A. Vargas, Manoela D. Martins
Wed Sep 02, 2020 15:42
Publication date: October 2020Source: European Journal of Cancer, Volume 138Author(s): Karla A. Lee, Heather M. Shaw, Veronique Bataille, Paul Nathan, Tim D. Spector
Wed Sep 02, 2020 18:04
Publication date: October 2020Source: European Journal of Cancer, Volume 138Author(s): Yaoyao Zhang, Rui Gao, Hanxiao Chen, Wenming Xu, Yihong Yang, Xun Zeng, Xiaochi Sun, Sirui Zhang, Xiao Hu, Lang Qin
Wed Sep 02, 2020 18:04
Publication date: October 2020Source: European Journal of Cancer, Volume 138Author(s): Nika Guberina, Christoph Pöttgen, Martin Schuler, Maja Guberina, Georgios Stamatis, Till Plönes, Bettina Krebs, Martin Metzenmacher, Dirk Theegarten, Thomas Gauler, Karl-Heinz Jöckel, Kaid Darwiche, Clemens Aigner, Martin Stuschke, Wilfried E. Eberhardt
Wed Sep 02, 2020 18:04
Future Oncology, Ahead of Print.
Wed Sep 02, 2020 13:33
Related Articles Micropapillary pattern of stage IIIA-N2 lung adenocarcinoma is a prognostic factor after adjuvant chemoradiotherapy. Future Oncol. 2020 Sep 01;: Authors: Zeng J, Cui X, Cheng L, Chen Y, Du X, Sheng L Abstract Aim: This study aims to investigate the significance of a micropapillary pattern in stage IIIA-N2 lung adenocarcinoma after adjuvant chemoradiotherapy. Patients & methods: A total of 257 patients with stage IIIA-N2...
Wed Sep 02, 2020 15:27
Related Articles The clinical significance of routine risk categorization in metastatic renal cell carcinoma and its impact on treatment decision-making: a systematic review. Future Oncol. 2020 Sep 01;: Authors: Bazarbashi S, Alsharm A, Azam F, Ashry HE, Zekri J Abstract Aim: To analyze responses to first-line metastatic renal cell carcinoma (mRCC) treatment stratified by risk criteria. Patients & methods: Clinical trials and observational...
Wed Sep 02, 2020 15:27
Related Articles Network meta-analysis of first-line therapy for advanced EGFR mutation positive non-small-cell lung cancer: updated overall survival. Future Oncol. 2020 Sep 01;: Authors: Farris MS, Larkin-Kaiser KA, Scory T, Boyne D, Wilner KD, Pastel M, Cappelleri JC, Ivanova JI Abstract Aim: To update overall survival (OS) results from a previous network meta-analysis comparing the relative clinical efficacy of epidermal growth factor receptor-targeted...
Wed Sep 02, 2020 15:27
Abstract In designing national strategies for genetic testing, it is important to define the full spectrum of pathogenic mutations in prostate cancer (PCa) susceptibility genes. To investigate the frequency of mutations in PCa susceptibility genes in Polish familial PCa cases, to estimate gene‐related PCa risks and probability of aggressive disease, we analyzed the coding regions of 14 genes by exome sequencing in 390 men with familial prostate cancer and 308 cancer‐free controls. We compared the...
Tue Sep 01, 2020 19:31
Abstract Large oncology repositories have paired genomic and transcriptomic data for all patients. We used these data to perform two independent analyses: to identify gene expression changes related to a gene mutation and to identify mutations altering the expression of a selected gene. All data processing steps were performed in the R statistical environment. RNA‐sequencing and mutation data were acquired from TCGA. The DESeq2 algorithm was applied for RNA‐seq normalization, and transcript variants...
Tue Sep 01, 2020 19:31
Abstract In aNSCLC, stopping nivolumab after 12 months (mo) negatively affects outcomes. We performed a world data‐based analysis assessing the value of nivolumab continuation and optimal dosing beyond 24mo. Out of 697 consecutive patients with aNSCLC in whom nivolumab was initiated between 2015‐2018, 45 patients receiving nivolumab for ≥24mo were selected. These were divided into groups A: nivolumab administered at a dose 3 mg/kg q2 weeks (w)/240 mg q2w/480 mg q4w, n = 25; B: nivolumab re‐scheduled...
Tue Sep 01, 2020 19:31
Abstract BRAF V600E mutations have been reported as a marker of sporadic microsatellite‐unstable (MSI) colorectal cancer (CRC). Current international diagnostic guidelines recommend BRAF mutation testing in MSI CRC patients to predict low risk of Lynch syndrome (LS). We evaluated the age‐specific performance of BRAF testing in LS diagnostics. We systematically compared the prevalence of BRAF mutations in LS‐associated CRCs and unselected MSI CRCs in different age groups as available from published...
Tue Sep 01, 2020 19:30
Abstract The evolutionary dynamics of human cancers has been investigated popularly and several bifurcated paths in cancer evolutionary trajectories are revealed to be with differential outcomes and phenotypes. However, whether such bifurcated paths exist in glioblastoma (GBM) remains unclear. In 385 GBM samples, through determining the clonal status of cancer driver events and inferring their temporal order, we constructed a temporal map of evolutionary trajectories at the patient population level....
Tue Sep 01, 2020 19:29
Abstract The Be Clear on Cancer (BCoC) campaigns have run in England since 2010. They aim to raise awareness of possible cancer symptoms, encouraging people to consult the GP with these symptoms. This study provides an overview of the impact of 11 national campaigns, for bowel, lung, bladder and kidney, breast and oesophago‐gastric cancers. We synthesised existing results for each campaign covering seven clinical metrics across the patient pathway, from primary care attendances to one‐year net survival....
Tue Sep 01, 2020 19:27
Abstract High serum levels of IL‐6 correlate with poor prognosis and chemotherapy resistance in several cancers. The underlying mechanisms and its effects on immunotherapy are largely unknown. To address this, we developed a human papillomavirus type 16 (HPV16)‐associated tumor model expressing IL‐6 to investigate the impact of tumor‐expressed IL‐6 during cisplatin chemotherapy and HPV16 synthetic long peptide vaccination as immunotherapy. The effect of tumor‐produced IL‐6 on tumor growth, survival...
Tue Sep 01, 2020 19:27
Abstract In this systematic review and meta‐analyses, we sought to determine sex‐disparities in treatment abandonment in children with cancer in low‐ and middle‐income countries (LMICs) and identify the characteristics of children and their families most disadvantaged by such abandonment. Sex‐disaggregated data on treatment abandonment were collated from the available literature and a random‐effects meta‐analysis was conducted to compare the rates in girls with those in boys. Subgroup analyses were...
Tue Sep 01, 2020 19:27
Abstract In Ethiopia, cervical cancer is the second leading cause of morbidity and mortality from all cancers in women. Persistent infection with human papillomaviruses (HPV) plays a key role in the development of cervical intraepithelial neoplasia and invasive cervical cancer. To establish baseline data on the population‐based prevalence of HPV infection and genotype distribution, we investigated cervical HPV epidemiology among rural women. This population‐based study was conducted among rural...
Tue Sep 01, 2020 19:26
Abstract The aim of this study was to develop and validate a machine learning algorithm to predict response of individual HER2‐amplified colorectal cancer liver metastases (lmCRC) undergoing dual HER2‐targeted therapy. Twenty‐four radiomics features were extracted following 3D manual segmentation of 141 lmCRC on pre‐treatment portal CT scans of a cohort including 38 HER2‐amplified patients; feature selection was then performed using genetic algorithms. lmCRC were classified as non‐responders (R‐),...
Tue Sep 01, 2020 19:25
Abstract This study reports preliminary data about the information needs of esophago-gastric cancer survivors and their supporters across diagnosis and treatment by identifying time-specific needs and whether the information provided aligned with the needs at each time point. Survivors (n = 26) and supporters (n = 15) were recruited from a public teaching hospital in South Australia. Both groups provided recall data describing personal information domain challenges at 6 clinically...
Wed Sep 02, 2020 03:00
Abstract This investigation aimed to study breast cancer awareness based on health information literacy and influential factors of breast cancer awareness among female nursing students in Changchun city in China. A four-part self-report questionnaire including the participants’ general demographic characteristics, the participants’ specialized characteristics concerning breast cancer screening, the Chinese version of the Breast Cancer Awareness Measurement (C-BCAM), and the Chinese...
Wed Sep 02, 2020 03:00
Abstract Purpose The aim of this study was to investigate DNA methylation alterations in non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinomas (HCCs). Methods Genome-wide DNA methylation analysis was performed using the Infinium Human Methylation 450 K BeadChip, and levels of mRNA expression were analyzed by quantitative...
Wed Sep 02, 2020 20:48
Abstract Background Checkpoint inhibitors (CKI) targeting PD-1 or PD-L1 are major therapies for the treatment of non-small cell lung cancer (NSCLC). Despite numerous studies of biological biomarkers, we currently lack a marker to predict CKI primary resistance. The aim of this study was to isolate clinical markers associated with the absence of efficacy of CKI used as monotherapy in NSCLC. ...
Wed Sep 02, 2020 20:48
Abstract Purpose Squamous cell carcinoma of the vulva (SQCV) is the fifth common cancer in women. Necessity of inguinal lymph node surgery depends on the depth of stromal invasion, inducing lymph node surgery, if depth of invasion is more than 1 mm. In this study we tested the prediction of stromal infiltration depth by measurements in preoperative biopsies. ...
Wed Sep 02, 2020 20:48
Abstract Purpose The epithelial-to-mesenchymal transition (EMT) phenotype-based subsets of circulating tumor cells (CTCs) might be predictors of tumor progression. We evaluated the clinical properties of different phenotypic CTCs in patients with non-small cell lung cancer (NSCLC). Secondly, we explored the association between different phenotypic CTCs and the uptake of 18F-fluorodeoxyglucose (FDG) by the primary tumor on a positron...
Wed Sep 02, 2020 20:48
Abstract Background Colorectal cancer (CRC) is now a major human cancer, and B-cell translocation gene 3 (BTG3) has been reported as a tumor-suppressor in CRC, but its upstream regulator has not been identified. Methods Endogenous expression levels of BTG3 were compared between normal colorectal cell line CCD-18Co and two CRC cell lines...
Wed Sep 02, 2020 20:48
Abstract Purpose COVID-19 is causing a lot of problems in health services around the world, especially in medical institutions receiving cancer patients. On March 12, China’s National Health Commission announced that the peak of the COVID-19 epidemic has passed in China. Thus, a proper arrangement of medication, surgery and radiotherapy for patients with cancer is of vital importance after the epidemic peak. ...
Wed Sep 02, 2020 20:48
Abstract Purpose Fatigue is a distressing symptom in head & neck cancer patients before during and at the end of curative therapy. Pharmacologic and not pharmacologic treatments have been proposed with scarce or no evidence of efficacy. The aim of the study is to evaluate the efficacy of American ginseng in respect to placebo in reducing fatigue in patients treated for head and neck cancer with curative intent. ...
Wed Sep 02, 2020 20:48
Abstract Purpose Polypharmacy is a common problem among older adults. However, its prevalence and impact on the clinical outcomes of anticancer treatment, such as survival and adverse events, in older patients with advanced cancer have not been well investigated. Methods We retrospectively reviewed data from Japanese patients treated...
Wed Sep 02, 2020 20:48
The title of the article is incorrectly published in the original article. The correct article title is “Afatinib is active in osteosarcoma cell lines”.
Wed Sep 02, 2020 20:48
Abstract Background Primary pineal malignant melanoma (PPMM) is a rare entity of primary central nervous system melanomas, with only 26 cases reported in the literature to date. Case presentation We report the case of a 65-year-old male with a PPMM who has prolonged survival of more than 104 weeks after combined microsurgical and endoscopic...
Wed Sep 02, 2020 20:48
Abstract Purpose In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. Methods We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early...
Wed Sep 02, 2020 20:48
Abstract Introduction Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world. Recent research suggests that cancer stem cells (CSCs) are responsible for tumor cell’s malignant behavior in CRC. This study has been designed to determinate clinical implications of CSC markers: CD44, DCLK1, Lgr5, and ANXA2 in CRC. Materials and methods...
Wed Sep 02, 2020 20:48
Abstract Purpose The combined small-cell lung cancer (c-SCLC) is rare and has unique clinicopathological futures. The aim of this study is to investigate 18F-FDG PET/CT parameters and clinicopathological factors that influence the prognosis of c-SCLC. Methods Between November 2005 and October 2014, surgical-resected tumor samples from...
Wed Sep 02, 2020 20:48
Abstract Purpose Canonical Wnt/ β-catenin pathway is one mechanism being activated in platinum-resistant epithelial ovarian cancer (EOC). Detecting potential targets for Wnt pathway modulation as a putative future therapeutic approach was the aim of this study. Methods Biological effects of different Wnt modulators (SB216763, XAV939 and...
Wed Sep 02, 2020 20:48
Abstract Purpose Treatment strategies for low rectal cancer have been evolving toward achieving less treatment morbidity with the same oncological success—we aimed to assess the results of the new watch and wait (W&W) strategy in our cohort. Methods A tertiary care cohort study was conducted. New patients with rectal adenocarcinoma...
Wed Sep 02, 2020 20:48
Abstract Purpose Oral cancer is a still underestimated public health problem. In Germany, until 2007, there was no systematic approach available for the purpose of raising the awareness of the public. From 2007 to 2011, a concept was developed for such an approach, and the campaign was launched in Northern Germany in 2012, and concluded in 2014. This report aims at presenting incidence trends of oral cancer, stratified according...
Wed Sep 02, 2020 20:48
Abstract Background Despite great advances in its early diagnosis and treatment, lung cancer is still an intractable disease and the second leading cause of cancer-related deaths and morbidity in the world. The family of Polo-like kinases (PLKs) consists of five serine/threonine kinases, which have been reported to participate in various human diseases. However, the expression and prognostic value of each PLK in human lung cancer...
Wed Sep 02, 2020 20:48
Abstract Introduction Since the community spread of Coronavirus disease 2019 (COVID-19), the practice of oncologic care at our comprehensive cancer center has changed. Postponing cancer treatment without consideration of its implications could cost more lives than can be saved. In this special situation, we must continue to provide our cancer patients with the highest quality of medical services assuring the safety. This article...
Wed Sep 02, 2020 20:48
Abstract Purpose To evaluate the response rate and safety of superselective drug-eluting beats transarterial chemoembolization (DEB-TACE) with doxorubicin-loaded 40-µm microspheres in patients with hepatocellular carcinoma (HCC). Methods One hundred and forty-one treatments with doxorubicin-loaded 40-µm microspheres in 83 patients between 2012 and...
Wed Sep 02, 2020 03:00
Abstract Purpose This study aimed to evaluate the clinical effects of percutaneous vertebroplasty (PVP) combined with postoperative radiotherapy (RT) in the treatment of spinal metastases. Methods Nine patients (4 males and 5 females, mean age 59.56 years) with painful pathologic compression vertebral fractures caused by metastatic cancers of the spine...
Wed Sep 02, 2020 03:00
A pronounced polarization of healthcare resources and workforce towards the prevention of the rapid spread of SARS-CoV-2 occurred at the expenses of the majority of chronic diseases and cancer, thus jeopardizi...
Tue Sep 01, 2020 03:00
Maximal safe resection of malignant tissue is associated with improved progression-free survival and better response to radiation and chemotherapy for patients with glioblastoma (GBM). 5-Aminolevulinic acid (5-ALA) is the current FDA-approved standard for intraoperative brain tumor visualization. Unfortunately, autofluorescence in diffuse areas and high fluorescence in dense tissues significantly limit discrimination at tumor margins. This study is the first to compare 5-ALA to an investigational...
Wed Sep 02, 2020 10:05
Tyrosine kinase inhibitors have revolutionized the world of cancer treatment in recent years, profoundly improving survival of patients with chronic myeloid leukemia (CML) and beyond. However, off-target toxicities of these inhibitors are well-described, and resistance has become a paramount concern. Novel allosteric inhibitors of the Abelson (ABL) family of tyrosine kinases, including GNF-2, GNF-5, and ABL-001, are equipped to overcome these issues. Several contemporary studies have demonstrated...
Wed Sep 02, 2020 10:05
Despite advances in the treatment of acute myeloid leukemia (AML), novel therapies are needed to induce deeper and more durable clinical response. Bispecific T-cell Engager (BiTE) molecules, which redirect patient T cells to lyse tumor cells, are a clinically validated modality for hematologic malignancies. Due to broad AML expression and limited normal tissue expression, fms-related tyrosine kinase 3 (FLT3) is proposed to be an optimal BiTE molecule target. Expression profiling of FLT3 was performed...
Wed Sep 02, 2020 10:05
Antibody–drug conjugates (ADC) are targeted agents that have shown promise in treating cancer. A central challenge in development of ADCs is the relatively narrow therapeutic index observed in clinical studies. Patient selection strategies based on expression of the target in tumors have the potential to maximize benefit and provide the best chance of clinical success; however, implementation of biomarker-driven trials can be difficult both practically and scientifically. We conducted a survey of...
Wed Sep 02, 2020 10:05
Tipifarnib is a potent and highly selective inhibitor of farnesyltransferase (FTase). FTase catalyzes the posttranslational attachment of farnesyl groups to signaling proteins that are required for localization to cell membranes. Although all RAS isoforms are FTase substrates, only HRAS is exclusively dependent upon farnesylation, raising the possibility that HRAS-mutant tumors might be susceptible to tipifarnib-mediated inhibition of FTase. Here, we report the characterization of tipifarnib activity...
Wed Sep 02, 2020 10:05
Glucocorticoids are widely used for therapy of hematologic malignancies. Unfortunately, chronic treatment with glucocorticoids commonly leads to adverse effects including skin and muscle atrophy and osteoporosis. We found recently that REDD1 (regulated in development and DNA damage 1) plays central role in steroid atrophy. Here, we tested whether REDD1 suppression makes glucocorticoid-based therapy of blood cancer safer. Unexpectedly, approximately 50% of top putative REDD1 inhibitors selected by...
Wed Sep 02, 2020 10:05
Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma with a proclivity for systemic dissemination, leading many patients to present with advanced stage disease and fail available treatments. There is a notable lack of targeted therapies for NPC, despite working knowledge of multiple proteins with integral roles in NPC cancer biology. These proteins include EZH2, Snail, eIF4E, and IMPDH, which are all overexpressed in NPC and correlated with poor prognosis. These proteins are known to be modulated...
Wed Sep 02, 2020 10:05
Abnormal activity of human prolactin (PRL) and its membrane-associated receptor (PRLR) contributes to the progression of uterine carcinoma. However, the underlying mechanisms are not well understood, and current means of targeting the PRL/PRLR axis in uterine cancer are limited. Our integrated analyses using The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) databases demonstrated that a short form of PRLR (PRLR_SF) is the isoform predominantly expressed in human uterine cancers; expression...
Wed Sep 02, 2020 10:05
Despite significant progress in understanding the genetic landscape of T-cell acute lymphoblastic leukemia (T-ALL), the discovery of novel therapeutic targets has been difficult. Our results demonstrate that the levels of PIM1 protein kinase is elevated in early T-cell precursor ALL (ETP-ALL) but not in mature T-ALL primary samples. Small-molecule PIM inhibitor (PIMi) treatment decreases leukemia burden in ETP-ALL. However, treatment of animals carrying ETP-ALL with PIMi was not curative. To model...
Wed Sep 02, 2020 10:05
Trastuzumab and the related ADC, ado-trastuzumab emtansine (T-DM1), both target HER2-overexpressing cells. Together, these drugs have treatment indications in both early-stage and metastatic settings for HER2+ breast cancer. T-DM1 retains the antibody functionalities of trastuzumab and adds the potency of a cytotoxic maytansine payload. Interestingly, in the clinic, T-DM1 cannot always replace the use of trastuzumab plus chemotherapy administered together as single agents. We hypothesize that this...
Wed Sep 02, 2020 10:05
Conventional antibody–drug conjugates (ADC) utilize native surface-exposed lysines or cysteines on the antibody of interest to conjugate cytotoxic payload. The nonspecific conjugation results in a mixture with variable drug-to-antibody ratios (DAR), conjugation sites, and ADCs that are often unstable in systemic circulation. ARX788 is an ADC consisting of a HER2-targeting antibody site-specifically conjugated with a potent antitubulin cytotoxic drug-linker, AS269. The site-specific conjugation is...
Wed Sep 02, 2020 10:05
Next-generation sequencing of solid tumors has revealed variable signatures of immunogenicity across tumors, but underlying molecular characteristics driving such variation are not fully understood. Although expression of endogenous retrovirus (ERV)-containing transcripts can provide a source of tumor-specific neoantigen in some cancer models, associations between ERV levels and immunogenicity across different types of metastatic cancer are not well established. We performed bioinformatics analysis...
Wed Sep 02, 2020 10:05
First-generation antibody–drug conjugates (ADC) are heterogeneous mixtures that have shown clinical benefit, but generally exhibited safety issues and a narrow therapeutic window due, in part, to off-target toxicity caused by ADC instability. ARX788 is a next-generation, site-specific anti-HER2 ADC that utilizes a unique nonnatural amino acid–enabled conjugation technology and a noncleavable Amberstatin (AS269) drug-linker to generate a homogeneous ADC with a drug-to-antibody ratio of 1.9. ARX788...
Wed Sep 02, 2020 10:05
Mitotane causes hypercholesterolemia in patients with adrenocortical carcinoma (ACC). We suppose that cholesterol increases within the tumor and can be used to activate proliferative pathways. In this study, we used statins to decrease intratumor cholesterol and investigated the effects on ACC growth related to estrogen receptor α (ERα) action at the nuclear and mitochondrial levels. We first used microarray to investigate mitotane effect on genes involved in cholesterol homeostasis and evaluated...
Wed Sep 02, 2020 10:05
We previously reported that silencing of the PRR gene, which encodes the (pro)renin receptor [(P)RR], significantly reduced Wnt/β-catenin–dependent development of pancreatic ductal adenocarcinoma (PDAC). Here, we examined the effects of a panel of blocking mAbs directed against the (P)RR extracellular domain on proliferation of the human PDAC cell lines PK-1 and PANC-1 in vitro and in vivo. We observed that four rat anti-(P)RR mAbs induced accumulation of cells in the G0–G1-phase of the cell cycle...
Wed Sep 02, 2020 10:05
Although intravesical bacillus Calmette-Guérin (BCG) immunotherapy has been the gold standard for nonsurgical management of non–muscle-invasive bladder cancer, a considerable number of patients exhibit resistance to the adjuvant treatment with unexplained mechanisms. This study aimed to investigate whether and how androgen receptor (AR) signals modulate BCG cytotoxicity in bladder cancer. AR knockdown or overexpression in bladder cancer lines resulted in induction or reduction, respectively, in intracellular...
Wed Sep 02, 2020 10:05
Antibody–drug conjugates (ADC) containing pyrrolobenzodiazepine (PBD) dimers are being evaluated clinically in both hematologic and solid tumors. These include ADCT-301 (camidanlumab tesirine) and ADCT-402 (loncastuximab tesirine) in pivotal phase II trials that contain the payload tesirine, which releases the PBD dimer warhead SG3199. An important consideration in future clinical development is acquired resistance. The aim was to generate and characterize PBD acquired resistant cell lines in both...
Wed Sep 02, 2020 10:05
Menin serves both tumor suppressor and promoter roles in a highly tumor-specific manner. In colorectal cancer (CRC) menin is over-expressed and plays a critical role in regulating transcription of SKP2, and combined treatment with a menin inhibitor (MI) and small molecule EGFR inhibitor (EGFRi) leads to synergistic killing of CRC cells. However, the full spectrum of menin function in CRC remains uncertain. Herein, we demonstrate that menin inhibition increases glycolysis in CRC cells. This MI-induced...
Wed Sep 02, 2020 18:48
Acute myeloid leukemia (AML) is the most common and aggressive blood cancer in adults. In particular, significant unmet medical needs exist for effective treatment strategies for M4 and M5 AML subtypes. Antibody-drug conjugates (ADCs) are a promising drug class for AML therapy, as demonstrated by the FDA-approved anti-CD33 ADC gemutuzumab ozogamicin (Mylotarg®). However, CD33 is expressed in normal hematopoietic stem cells, highlighting the critical need to identify AML-specific targets to minimize...
Wed Sep 02, 2020 18:48
Pancreatic cancer has poor prognosis and treatment outcomes due to its highly metastatic nature and resistance to current treatments. The RNA binding protein (RBP) Hu-antigen R (HuR) is a central player in posttranscriptional regulation of cancer related gene expression, and contributes to tumorigenesis, tumor growth, metastasis and drug resistance. HuR has been suggested to regulate pancreatic cancer epithelial to mesenchymal transition (EMT) but the mechanism was not well understood. Here we further...
Wed Sep 02, 2020 18:48
One-carbon (1C) metabolism encompasses folate-mediated 1C transfer reactions and related processes, including nucleotide and amino acid biosynthesis, antioxidant regeneration, and epigenetic regulation. 1C pathways are compartmentalized in the cytosol, mitochondria and nucleus. 1C metabolism in the cytosol has been an important therapeutic target for cancer since the inception of modern chemotherapy and "antifolates" targeting cytosolic 1C pathways continue to be a mainstay of the chemotherapy armamentarium...
Wed Sep 02, 2020 18:48
Abstract CD46 (also known as membrane cofactor protein), which is a member of the membrane‐bound complement regulatory protein family, has been reported to cause cancer cells to escape complement‐dependent cytotoxicity. However, the association between CD46 polymorphisms and the risk of hepatocellular carcinoma (HCC) has not been investigated. This two‐stage association study was conducted to assess the relationship between the tagging single nucleotide polymorphisms (tagSNPs) of CD46 and HCC risk...
Tue Sep 01, 2020 14:14
Head and neck cancer patients frequently require surgery and postoperative radiotherapy. Whenever tumor resection involves large tissue volumes, reconstructive surgery is usually needed. Reconstructive surgery frequently involves the use of autologous flaps, placed at the tumour bed to compensate for the loss of substance [1,2]. Autologous flaps are units of tissue that are harvested at a donor site and transferred to a recipient site in a same individual. Autologous flaps can be made of muscle,...
Wed Sep 02, 2020 03:00
Laryngeal cancer is a common head and neck malignancy, affecting approximately 13,000 patients annually in the United States.[1] Over 75% of laryngeal cancers involve the true vocal cords, which are often detected at an early stage and highly curable by single-modality therapy using surgery or radiation. [2,3]Hypofractionated treatment has shown promising results, but reports of local recurrence and severe larynx toxicities clearly show the need for further investigation.[4–6] We have successfully...
Wed Sep 02, 2020 03:00
Radiation with or without chemotherapy is frequently the treatment of choice for patients with locally-advanced head and neck cancer (HNC) [1]. However, it has been associated with significant organ-at-risk (OAR) toxicity, including xerostomia, dysphagia and loss of taste [2,3,4]. Substantial resources have been invested in developing more advanced radiotherapy planning and treatment techniques like intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) with the...
Wed Sep 02, 2020 03:00
Neoadjuvant chemoradiotherapy (NACRT) combined with total mesorectal excision (TME) is regarded as the standard treatment choice in decreasing local recurrence, distant metastasis and prolonging the disease-free survival (DFS) for locally advanced rectal cancer (LARC)[1]. At present, the pathological criterion for assessing the curative response is by pathological tumor regression grade (pTRG), and this is classified according to the proportion of fibrosis and residual tumor cells of the specimen.
Wed Sep 02, 2020 03:00
The treatment of uveal melanoma with proton therapy has a long and successful history, with more than 30’000 patients having been treated worldwide, achieving tumor control rates at 5 years of well over 90% [1] [2] [3]. Of these, more than 20% of all such treatments have been delivered at Paul Scherrer Institut (PSI), with tumor control rates reaching 98% [4] [5].
Wed Sep 02, 2020 03:00
Patients treated in the past with thoracic radiotherapy (RT) for cancers such as Hodgkin lymphoma (HL) and childhood cancer (CC) have been at risk from radiation-related heart disease (RRHD), often manifesting decades later, due to incidental cardiac radiation during RT [1,2]. Consequently, for patients being considered for thoracic RT today, dose-response relationships between the radiation dose to the heart and the risk of RRHD help RT professionals when balancing the risks associated with RT with...
Wed Sep 02, 2020 03:00
Patients with head and neck cancer (HNC) often experience trismus - a limited mouth opening induced by cancer treatment such as radiotherapy, concomitant chemoradiotherapy, or tumor surgery or by long-term chewing of irritating agents such as betel nuts [1,2]. Radiotherapy is the main reason for oral tissue change and a higher incidence of trismus was found among patients undergoing radiotherapy compared with those undergoing other forms of treatment. Posttreatment trismus incidence rate ranges from...
Wed Sep 02, 2020 03:00
Publication date: October 2020Source: Cancer Epidemiology, Volume 68Author(s): Sandra Mavoungou, Paula Rios, Hélène Pacquement, Marie Nolla, Charlotte Rigaud, Mathieu Simonin, Yves Bertrand, Anne Lambilliotte, Laure Faure, Laurent Orsi, Jacqueline Clavel, Audrey Bonaventure
Wed Sep 02, 2020 18:45
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