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Paola Queirolo, Francesco Spagnolo, Virginia Picasso, Laura Spano, Enrica Tanda, Valeria Fontana, Laura Giorello, Domenico Franco Merlo, Ester Simeone, Antonio Maria Grimaldi, Marcello Curvietto, Michele Del Vecchio, Paolo Bruzzi, Paolo Antonio Ascierto
Background: BRAF inhibitor vemurafenib achieves high response rate and an improvement in survival in patients with BRAF-mutated metastatic melanoma. However, median progression-free survival is only 6.9 months in the phase 3 study. Retrospective analyses suggest that treatment with BRAF inhibitors beyond initial progression might be associated with improved overall survival. We aimed to prospectively investigate the activity of prolonged treatment with vemurafenib and the addition of fotemustine in patients with systemic progression on prior single-agent BRAF inhibitor...
February 23, 2018: Oncotarget
Yuanyuan Wang, Jiaojiao Gu, Xiangde Lin, Wei Yan, Wenchao Yang, Guoyang Wu
Thyroid cancer is one of the most common types of cancer in the endocrine system. Among all types of thyroid cancer, papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Long non-coding RNA (lncRNA) BRAF-activated non-protein-coding RNA (BANCR) is a 688-bp-long nucleotide transcript, which was first identified in melanoma. The function of BANCR in thyroid cancer remains unclear. The aim of the present study was to investigate whether BANCR is involved in the development of thyroid cancer...
April 2018: Oncology Letters
Qiang Zuo, Jing Liu, Liping Huang, Yifei Qin, Teresa Hawley, Claire Seo, Glenn Merlino, Yanlin Yu
Multiple genetic mutations within melanoma not only cause lesion-specific responses to targeted therapy but also alter the molecular route of resistance to that therapy. Inactivation of PTEN occurs in up to 30% of melanomas, frequently with a concurrent activating BRAF mutation. PTEN loss regulates both acquired and intrinsic drug resistance. Here we show that AXL/AKT axis mediated-resistance to BRAF inhibitor (BRAFi) depends upon PTEN status in melanoma. Hyperactivation of both ERK and AKT pathways was associated with BRAFi resistance in melanoma with wildtype PTEN...
March 19, 2018: Oncogene
Emily Capone, Alessia Lamolinara, Daniela D'Agostino, Cosmo Rossi, Vincenzo De Laurenzi, Manuela Iezzi, Stefano Iacobelli, Gianluca Sala
Cutaneous melanoma is one of the cancers with the fastest rising incidence and in its advanced metastatic form is a highly lethal disease. Despite the recent approval of several new drugs, the 5-year overall survival rate for advanced cutaneous melanoma is still below 20% and therefore, the development of novel treatments remains a primary need. Antibody-Drug Conjugates are an emerging novel class of anticancer agents, whose preclinical and clinical development has recently seen a remarkable increase in different tumors, including melanoma...
March 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Qiushi Sun, Yuan Liu, Bo Liu, Yingying Liu
BACKGROUND: Patients with colorectal cancer (CRC) who are sensitive to epidermal growth factor antibodies inevitably acquire drug resistance. This study aimed to determine the usefulness of liquid biopsies for prognosis and clinical correlation. MATERIALS AND METHODS: For liquid biopsy tests, we extracted blood from 140 CRC patients with matched tumor samples. Circulating tumor cells (CTCs) and tumor DNA (ctDNA) were extracted before surgery and treatment. Samples were quantified and tested for mutations in KRAS, NRAS and BRAF...
March 2018: American Journal of the Medical Sciences
A Campennì, R M Ruggeri, M Siracusa, S A Pignata, F Di Mauro, A Vento, F Trimarchi, S Baldari
PURPOSE: The aim of the present study was to evaluate the possible diagnostic role of the combined performance of BRAF mutation analysis and MIBI scintigraphy in papillary thyroid cancer (PTC) patients with incomplete bio-chemical response to first radioiodine therapy (RAIT) performed for thyroid remnant ablation. METHODS: The records of 15 PTC patients with bio-chemical incomplete response to first RAIT were retrospectively analyzed. BRAFV600E analysis on primary tumor samples was obtained in all cases along with neck ultrasonography and99m Tc-MIBI scintigraphy of the neck-thorax regions at first follow-up...
March 16, 2018: Journal of Endocrinological Investigation
Sara Valpione, Matteo S Carlino, Johanna Mangana, Meghan J Mooradian, Grant McArthur, Dirk Schadendorf, Axel Hauschild, Alexander M Menzies, Ana Arance, Paolo A Ascierto, AnnaMaria Di Giacomo, Francesco de Rosa, James Larkin, John J Park, Simone M Goldinger, Ryan J Sullivan, Wen Xu, Elisabeth Livingstone, Michael Weichenthal, Rajat Rai, Lydia Gaba, Georgina V Long, Paul Lorigan
No abstract text is available yet for this article.
March 13, 2018: European Journal of Cancer
Yang Zou, Jiang-Yan Zhou, Jiu-Bai Guo, Li-Qun Wang, Yong Luo, Zi-Yu Zhang, Fa-Ying Liu, Jun Tan, Feng Wang, Ou-Ping Huang
Endometriosis is a potential premalignant disorder. The underlying molecular aberrations, however, are not fully understood. A recent exome sequencing study found that 25% (10/39) of deep infiltrating endometriosis harbored cancer driver gene mutations. However, it is unclear whether these mutations also exist in ovarian endometriosis. Here, a total of 101 ovarian endometriosis samples were analyzed for the presence of these gene mutations, including KRAS, PPP2R1A, PIK3CA and ARID1A. In addition, 6 other cancer-associated genes (BRAF, NRAS, HRAS, ERK1, ERK2 and PTEN) were also analyzed...
March 9, 2018: Mutation Research
Ruiting Lin, Siyuan Xia, Changliang Shan, Dong Chen, Yijie Liu, Xue Gao, Mei Wang, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Michael Rossi, Ragini R Kudchadkar, David H Lawson, Fadlo R Khuri, Sagar Lonial, Jing Chen
Dietary supplements such as vitamins and minerals are widely used in the hope of improving health but may have unidentified risks and side effects. In particular, a pathogenic link between dietary supplements and specific oncogenes remains unknown. Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors...
March 15, 2018: Molecular Cell
Kenneth D Swanson, Bin Zheng
In this issue of Molecular Cell, Lin et al. (2018) report that chondroitin-4-sulfate, which is found in a common supplement meant to alleviate degenerative joint disorders, promotes the growth of BRAF V600E mutant melanoma. This study not only has implications for patient care but also sheds light on a novel mechanism for regulating phosphoinositide 3-kinase signaling.
March 15, 2018: Molecular Cell
Hironori Aoki, Eiichiro Yamamoto, Hiro-O Yamano, Tamotsu Sugai, Tomoaki Kimura, Yoshihito Tanaka, Hiro-O Matsushita, Kenjiro Yoshikawa, Ryo Takagi, Eiji Harada, Michiko Nakaoka, Yuko Yoshida, Taku Harada, Gota Sudo, Makoto Eizuka, Akira Yorozu, Hiroshi Kitajima, Takeshi Niinuma, Masahiro Kai, Masanori Nojima, Hiromu Suzuki, Hiroshi Nakase
BACKGROUND: Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. AIMS: We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. METHODS: A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L)...
March 15, 2018: Digestive Diseases and Sciences
Stephan Bartels, Akinyele Adisa, Timothy Aladelusi, Juliana Lemound, Angelika Stucki-Koch, Sami Hussein, Hans Kreipe, Christian Hartmann, Ulrich Lehmann, Kais Hussein
The aim of this study was to evaluate the mutation profile of BRAF wild-type craniopharyngiomas and ameloblastomas. Pre-screening by immunohistochemistry and pyrosequencing for identifying BRAF wild-type tumors was performed on archived specimens of ameloblastic tumors (n = 20) and craniopharyngiomas (n = 62). Subsequently, 19 BRAF wild-type tumors (nine ameloblastic tumors and ten craniopharyngiomas) were analyzed further using next-generation sequencing (NGS) targeting hot spot mutations of 22 cancer-related genes...
March 15, 2018: Virchows Archiv: An International Journal of Pathology
Weinan Guo, Jinyuan Ma, Tianli Pei, Tao Zhao, Sen Guo, Xiuli Yi, Yu Liu, Shiyu Wang, Guannan Zhu, Zhe Jian, Tianwen Gao, Chunying Li, Wenjun Liao, Qiong Shi
Melanoma is the most malignant skin cancer with increasing incidence worldwide. Although innovative therapies such as BRAF inhibitor and immune checkpoint inhibitor have gained remarkable advances, metastatic melanoma remains an incurable disease for its notorious aggressiveness. Therefore, further clarification of the underlying mechanism of melanoma pathogenesis is critical for the improvement of melanoma therapy. Ubiquitination is an important regulatory event for cancer hallmarks and melanoma development, and the deubiquitinating enzymes including ubiquitin-specific peptidase (USP) families are greatly implicated in modulating cancer biology...
March 14, 2018: Journal of Cellular and Molecular Medicine
Antoneicka L Harris, Samantha E Lee, Louis K Dawson, Laura A Marlow, Brandy H Edenfield, William F Durham, Thomas J Flotte, Michael Thompson, Daniel L Small, Aidan J Synnott, Svetomir N Markovic, John A Copland
Patient-derived tumor xenograft (PDTX) mouse models were used to discover new therapies for naïve and drug resistant BRAF V600E -mutant melanoma. Tumor histology, oncogenic protein expression, and antitumor activity were comparable between patient and PDTX-matched models thereby validating PDTXs as predictive preclinical models of therapeutic response in patients. PDTX models responsive and non-responsive to BRAF/MEK standard of care (SOC) therapy were used to identify efficacious combination therapies. One such combination includes a CDK4/6 inhibitor that blocks cell cycle progression...
February 16, 2018: Oncotarget
Guangzhong Xu, Kai Li, Nengwei Zhang, Bin Zhu, Guosheng Feng, Qing Fan
Colorectal cancer is a common malignancy with a high prevalence and associated mortality rate. However, the preclinical tools currently used for drug development are insufficient. The aim of the present study was to establish and characterize a specific patient-derived colon cancer xenograft (PDCCX) mouse model for drug testing. Primary colon tumors were obtained from 10 patients by surgical resection, and tumor tissues were subsequently grafted into nude mice followed by consecutive passages. Primary tumors and xenograft tumors were collected and processed for DNA sequencing, histological evaluation and immunohistochemical staining...
April 2018: Oncology Letters
Lihua Huang, Xuming Wang, Xuan Huang, Huawei Gui, Yan Li, Qiongxia Chen, Dongling Liu, Lijiang Liu
The aim of the present study was to examine the rate of BRAF mutation and the expression profiles of CK19, galectin-3, CD56, thyroid peroxidase (TPO) and Ki67 in papillary thyroid carcinoma (PTC) and papillary thyroid micro-carcinoma (PTMC). A total of 246 cases of thyroid disease were collected, including PTC, PTMC, nodular goiter (NG) and Hashimoto thyroiditis (HT). The results revealed that CK19 expression was 116/120 in PTC, 61/64 in PTMC, 2/34 in NG and 1/28 in HT. Galectin-3 positive expression was 115/120 in PTC, 60/64 in PTMC, 6/34 in NG and 4/28 in HT...
April 2018: Oncology Letters
Nina Zila, Andrea Bileck, Besnik Muqaku, Lukas Janker, Ossia M Eichhoff, Phil F Cheng, Reinhard Dummer, Mitchell P Levesque, Christopher Gerner, Verena Paulitschke
Background: MAP kinase inhibitor (MAPKi) therapy for BRAF mutated melanoma is characterized by high response rates but development of drug resistance within a median progression-free survival (PFS) of 9-12 months. Understanding mechanisms of resistance and identifying effective therapeutic alternatives is one of the most important scientific challenges in melanoma. Using proteomics, we want to specifically gain insight into the pathophysiological process of cerebral metastases. Methods: Cerebral metastases from melanoma patients were initially analyzed by a LC-MS shotgun approach performed on a QExactive HF hybrid quadrupole-orbitrap mass spectrometer...
2018: Clinical Proteomics
Matthew Dankner, April A N Rose, Shivshankari Rajkumar, Peter M Siegel, Ian R Watson
The RAS-RAF-MEK-ERK signaling cascade is among the most frequently mutated pathways in human cancer. Approximately 50% of melanoma patients possess a druggable hotspot V600E/K mutation in the BRAF protein kinase. FDA-approved combination therapies of BRAF and MEK inhibitors are available that provide survival benefits to patients with a BRAF V600 mutation. Non-V600 BRAF mutants are found in many cancers, and are more prevalent than V600 mutations in certain tumor types. For example, between 50-80% of BRAF mutations in non-small cell lung cancer and 22-30% in colorectal cancer encode for non-V600 mutants...
March 15, 2018: Oncogene
F Pietrantonio, F Di Nicolantonio, A B Schrock, J Lee, F Morano, G Fucà, P Nikolinakos, A Drilon, J F Hechtman, J Christiansen, K Gowen, G M Frampton, P Gasparini, D Rossini, C Gigliotti, S T Kim, M Prisciandaro, J Hodgson, A Zaniboni, V K Chiu, M Milione, R Patel, V Miller, A Bardelli, L Novara, L Wang, S Pupa, G Sozzi, J Ross, M Di Bartolomeo, A Bertotti, S Ali, L Trusolino, A Falcone, F de Braud, C Cremolini
Background: Recognition of rare molecular subgroups is a challenge for precision oncology and may lead to tissue-agnostic approval of targeted agents. Here we aimed to comprehensively characterize the clinical, pathological and molecular landscape of RET rearranged metastatic colorectal cancer (mCRC). Patients and methods: In this case series, we compared clinical, pathological and molecular characteristics of 24 RET rearranged mCRC patients with those of a control group of 291 patients with RET negative tumors...
March 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Meenakshi Mehrotra, Rajesh R Singh, Sanam Loghavi, Dzifa Yawa Duose, Bedia A Barkoh, Carmen Behrens, Keyur P Patel, Mark J Routbort, Scott Kopetz, Russell R Broaddus, L Jeffrey Medeiros, Ignacio I Wistuba, Rajyalakshmi Luthra
A suitable clinical-grade platform is required for detection of somatic mutations with high sensitivity in cell-free DNA (cfDNA) of patients with solid tumors. In this study, we evaluated in parallel ultra-deep NGS with MassARRAY and allele-specific droplet digital PCR (ddPCR) for cfDNA genotyping and correlated cfDNA yield and mutation status with overall survival (OS) of patients. We assessed plasma samples from 46 patients with various advanced metastatic solid tumors and known mutations by deep sequencing using an Ampliseq cancer hotspot panel V2 on Ion Proton...
February 13, 2018: Oncotarget
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