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Targeted Oncology

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https://www.readbyqxmd.com/read/29656320/the-role-of-mesothelin-as-a-diagnostic-and-therapeutic-target-in-pancreatic-ductal-adenocarcinoma-a-comprehensive-review
#1
Federico Nichetti, Antonio Marra, Francesca Corti, Alessandro Guidi, Alessandra Raimondi, Natalie Prinzi, Filippo de Braud, Sara Pusceddu
Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. Based on a strong preclinical rationale, a number of therapeutic agents targeting mesothelin have entered clinical trials, including immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and adoptive T cell therapies with chimeric antigen receptors...
April 14, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29644577/the-impact-of-dose-and-simultaneous-use-of-acid-reducing-agents-on-the-effectiveness-of-vemurafenib-in-metastatic-braf-v600-mutated-melanoma-a-retrospective-cohort-study
#2
Lotte M Knapen, Rutger H T Koornstra, Johanna H M Driessen, Bas van Vlijmen, Sander Croes, Stein Schalkwijk, Angela Colbers, Winald R Gerritsen, David M Burger, Frank de Vries, Nielka P van Erp
BACKGROUND: The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown. OBJECTIVES: To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs. PATIENT AND METHODS: A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012-March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital...
April 11, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29633072/association-of-expression-levels-or-activation-status-of-stat3-with-treatment-outcomes-of-sunitinib-in-patients-with-renal-cell-carcinoma
#3
Kazuhiro Yamamoto, Takuto Hara, Tsutomu Nakagawa, Midori Hirai, Hideaki Miyake, Masato Fujisawa, Ikuko Yano
BACKGROUND: The expression level of signal transducer and activator of transcription 3 (STAT3) in tumor cells is reported to associate with response to therapy and with survival time in various types of cancer. OBJECTIVE: This retrospective study aimed to elucidate the association of STAT3 expression in tumor cells with the therapeutic outcomes of sunitinib in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic RCC who received sunitinib therapy were enrolled in this study...
April 9, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29623487/atezolizumab-in-metastatic-urothelial-carcinoma-outside-clinical-trials-focus-on-efficacy-safety-and-response-to-subsequent-therapies
#4
Pedro C Barata, Dhrmesh Gopalakrishnan, Vadim S Koshkin, Prateek Mendiratta, Matt Karafa, Kimberly Allman, Allison Martin, Jennifer Beach, Pam Profusek, Allison Tyler, Laura Wood, Moshe Ornstein, Timothy Gilligan, Brian I Rini, Jorge A Garcia, Petros Grivas
BACKGROUND: Little is known about the outcomes, safety, and response to subsequent therapies of patients with metastatic urothelial carcinoma (mUC) treated with atezolizumab outside clinical trials. OBJECTIVES: The objectives of the study include to report the clinical efficacy and safety of atezolizumab, and the response to future therapies in clinical practice outside clinical trials. PATIENT AND METHODS: This is a retrospective, single-center study including consecutive patients with confirmed mUC who received at least one dose of atezolizumab 1200 mg every 3 weeks between May 2016 and April 2017...
April 6, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29582224/ramucirumab-as-second-line-therapy-in-metastatic-gastric-cancer-real-world-data-from-the-ramoss-study
#5
Maria Di Bartolomeo, Monica Niger, Giuseppe Tirino, Angelica Petrillo, Rosa Berenato, Maria Maddalena Laterza, Filippo Pietrantonio, Federica Morano, Maria Antista, Sara Lonardi, Lorenzo Fornaro, Stefano Tamberi, Elisa Giommoni, Alberto Zaniboni, Lorenza Rimassa, Gianluca Tomasello, Teodoro Sava, Massimiliano Spada, Tiziana Latiano, Alessandro Bittoni, Alessandro Bertolini, Ilaria Proserpio, Katia Bruna Bencardino, Francesco Graziano, Giordano Beretta, Salvatore Galdy, Jole Ventriglia, Simone Scagnoli, Andrea Spallanzani, Raffaella Longarini, Ferdinando De Vita
BACKGROUND: Ramucirumab-alone or combined with paclitaxel-represents one of the main options for patients failing first-line treatment for advanced gastric cancer. OBJECTIVE: The RAMoss study aimed to evaluate the safety and efficacy profile of ramucirumab in the "real-life setting". PATIENTS AND METHODS: Patients from 25 Italian hospitals started therapy consisting of ramucirumab 8 mg/kg i.v. d1,15q28 with or without paclitaxel 80 mg/m2 i...
March 27, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29569164/prognostic-and-predictive-factors-for-renal-cell-carcinoma
#6
Cristina Suárez, Marc Campayo, Romà Bastús, Sergi Castillo, Olatz Etxanitz, Marta Guix, Núria Sala, Enrique Gallardo
Metastatic renal cell carcinoma (mRCC) is an incurable malignancy, characterized by its resistance to traditional chemotherapy, radiation, and hormonal therapy. Treatment perspectives and prognosis of patients with mRCC have been significantly improved by advances in the understanding of its molecular pathogenesis, which have led to the development of targeted therapeutics. Different molecular factors derived from the tumor or the host detected in both tissue or serum could be predictive of therapeutic benefit...
March 22, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29556925/antibody-drug-conjugates-for-the-treatment-of-hematological-malignancies-a-comprehensive-review
#7
Cédric Rossi, Marie-Lorraine Chrétien, René-Olivier Casasnovas
Antibody-drug conjugates (ADCs) are an emerging class of therapeutic agents that bring new opportunities for the treatment of hematological malignancies by meeting unmet medical needs. These drugs consist of a cytotoxic agent connected by a linker to a human, humanized, or chimeric antibody targeting a surface antigen specifically expressed by tumor cells. These ADCs are being developed to specifically deliver the cytotoxic agent into tumor cells. The cytotoxic payload is released from the ADC after internalization and cleavage of the linker, ultimately triggering the death of the cancer cell...
March 20, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29520705/targeting-bcl-2-in-hematologic-malignancies
#8
Nadia Khan, Brad Kahl
Resistance to apoptosis is one of the hallmarks of cancer and members of the B-cell lymphoma 2 (BCL-2) family of proteins are central regulators of apoptosis. Many cancers become resistant to chemotherapy and apoptosis by up-regulating BCL-2 and other family members, making these proteins attractive targets for cancer therapy. Venetoclax is an orally administered, small-molecule apoptosis stimulant that targets BCL-2 proteins by acting as a BCL-2 homology domain 3 (BH3) mimetic. The drug is approved in the USA and EU as a monotherapy for the for the treatment of certain patients with chronic lymphocytic leukemia (CLL) and is in phase III clinical development for multiple myeloma (MM), and in phase II or I/II clinical trials for acute myeloid leukemia, and several B-cell malignancies, including diffuse large B-cell lymphoma, Waldenstrom's macroglobulinaemia, follicular lymphoma, and mantle-cell lymphoma...
March 8, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29492762/cabozantinib-versus-standard-of-care-comparators-in-the-treatment-of-advanced-metastatic-renal-cell-carcinoma-in-treatment-na%C3%A3-ve-patients-a-systematic-review-and-network-meta-analysis
#9
Elvira Schmidt, Johanna Lister, Monika Neumann, Witold Wiecek, Shuai Fu, Anne-Lise Vataire, Jelena Sostar, Shengnan Huang, Florence Marteau
BACKGROUND: Cabozantinib has recently been evaluated as a first-line treatment in advanced renal cell carcinoma (aRCC). OBJECTIVE: To indirectly assess efficacy of cabozantinib versus standard-of-care (SoC) comparators in the first-line treatment of aRCC. METHODS: We conducted a systematic literature review (SLR) to identify randomized controlled studies in the first-line setting for aRCC. The outcomes analyzed were overall survival (OS) and progression-free survival (PFS)...
February 28, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29470785/the-abscopal-effect-in-the-era-of-cancer-immunotherapy-a-spontaneous-synergism-boosting-anti-tumor-immunity
#10
Zuzana Hlavata, Cinzia Solinas, Pushpamali De Silva, Michele Porcu, Luca Saba, Karen Willard-Gallo, Mario Scartozzi
Radiotherapy is one of the main treatment strategies used in cancer. Aside from the local control of the disease, which is mediated by a direct cytotoxic effect on tumor cells, radiotherapy has also been shown to exert immune-mediated local and systemic effects. Radiotherapy can elicit anti-tumor responses in distant sites from the radiation field; this phenomenon is known as the abscopal effect and has been described in patients previously treated with immune checkpoint blockade (ICB). Considering that the efficacy of immunotherapy has been demonstrated only in a subset of patients-who often benefit with lasting responses-efforts are ongoing to potentiate its activity with the development of new combination strategies...
February 22, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29441438/combining-ibrutinib-with-chk1-inhibitors-synergistically-targets-mantle-cell-lymphoma-cell-lines
#11
Valentina Restelli, Monica Lupi, Micaela Vagni, Rosaria Chilà, Francesco Bertoni, Giovanna Damia, Laura Carrassa
BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with an unfavorable clinical course. Besides deregulation of the cell cycle, B cell receptor (BCR) signaling, essential for MCL proliferation and survival, is also often deregulated due to constitutive activation of Bruton's tyrosine kinase (BTK). The BTK inhibitor ibrutinib has been approved as a therapy for refractory MCL, and while it shows some clinical activity, patients frequently develop primary or secondary ibrutinib resistance and have very poor outcomes after relapsing following ibrutinib treatment...
February 13, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29441437/immune-checkpoint-blockade-the-new-frontier-in-cancer-treatment
#12
Jeffrey M Clarke, Daniel J George, Stacey Lisi, April K S Salama
Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival...
February 13, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29423595/alpha-emitters-and-targeted-alpha-therapy-in-oncology-from-basic-science-to-clinical-investigations
#13
Mehran Makvandi, Edouard Dupis, Jonathan W Engle, F Meiring Nortier, Michael E Fassbender, Sam Simon, Eva R Birnbaum, Robert W Atcher, Kevin D John, Olivier Rixe, Jeffrey P Norenberg
Alpha-emitters are radionuclides that decay through the emission of high linear energy transfer α-particles and possess favorable pharmacologic profiles for cancer treatment. When coupled with monoclonal antibodies, peptides, small molecules, or nanoparticles, the excellent cytotoxic capability of α-particle emissions has generated a strong interest in exploring targeted α-therapy in the pre-clinical setting and more recently in clinical trials in oncology. Multiple obstacles have been overcome by researchers and clinicians to accelerate the development of targeted α-therapies, especially with the recent improvement in isotope production and purification, but also with the development of innovative strategies for optimized targeting...
February 8, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29423594/treatment-of-egfr-t790m-positive-non-small-cell-lung-cancer
#14
Joan Rou-En Choo, Chee-Seng Tan, Ross A Soo
The treatment of lung cancer has changed dramatically with the development of tyrosine kinase inhibitors (TKIs) that target sensitizing somatic mutations of the epidermal growth factor receptor (EGFR). Despite remarkable initial responses, patients eventually develop progressive disease, with the most common cause of resistance to first-line EGFR TKIs being the acquired T790M mutation. Various third-generation EGFR TKIs have been developed to specifically target this acquired mutation, of which osimertinib is currently the only approved agent...
February 8, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29423593/tumor-hypoxia-as-an-enhancer-of-inflammation-mediated-metastasis-emerging-therapeutic-strategies
#15
Josh W DiGiacomo, Daniele M Gilkes
Metastasis is the leading cause of cancer-related deaths. Recent research has implicated tumor inflammation as a promoter of metastasis. Myeloid, lymphoid, and mesenchymal cells in the tumor microenvironment promote inflammatory signaling amongst each other and together with cancer cells to modulate sustained inflammation, which may enhance cancer invasiveness. Tumor hypoxia, a state of reduced available oxygen present in the majority of solid tumors, acts as a prognostic factor for a worse outcome and is known to have a role in tumor inflammation through the regulation of inflammatory mediator signals in both cancer and neighboring cells in the microenvironment...
February 8, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29404898/induction-chemotherapy-with-the-extreme-regimen-in-frail-patients-with-locally-advanced-head-and-neck-squamous-cell-carcinoma
#16
Valérie Cochin, Erwan de Mones, Laurence Digue, Muriel Garcia-Ramirez, Charles Dupin, Claire Majoufre, Philipe Fernandez, Amaury Daste
BACKGROUND: Induction chemotherapy (IC) with TPF (docetaxel, cisplatin, 5FU) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) is limited to fit patients. OBJECTIVE: We conducted a retrospective cohort study to assess the use of the EXTREME regimen (platinum-based therapy, 5FU, cetuximab) as IC in frail patients with LAHNSCC. PATIENTS AND METHODS: Retrospective analysis of all consecutive patients with unresectable LAHNSCC treated with the EXTREME regimen, with or without 5FU as IC, from two French centers from 2008 to 2015...
February 5, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29374391/extracellular-vesicles-as-mirna-nano-shuttles-dual-role-in-tumor-progression
#17
Marzia Pucci, Pablo Reclusa Asiáin, Elena Duréndez Sáez, Eloisa Jantus-Lewintre, Mahafarin Malarani, Shahanavaj Khan, Simona Fontana, Aung Naing, Francesco Passiglia, Luis E Raez, Christian Rolfo, Simona Taverna
Tumor-derived extracellular vesicles (EVs) have a pleiotropic role in cancer, interacting with target cells of the tumor microenvironment, such as fibroblasts, immune and endothelial cells. EVs can modulate tumor progression, angiogenic switch, metastasis, and immune escape. These vesicles are nano-shuttles containing a wide spectrum of miRNAs that contribute to tumor progression. MiRNAs contained in extracellular vesicles (EV-miRNAs) are disseminated in the extracellular space and are able to influence the expression of target genes with either tumor suppressor or oncogenic functions, depending on both parental and target cells...
January 26, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29353436/biomarker-driven-therapy-in-metastatic-gastric-and-esophageal-cancer-real-life-clinical-experience
#18
Ofer Purim, Alexander Beny, Moshe Inbar, Katerina Shulman, Baruch Brenner, Elizabeth Dudnik, Felix Bokstein, Mark Temper, Dror Limon, Diana Matceyevsky, David Sarid, Amiel Segal, Valeriya Semenisty, Ronen Brenner, Tamar Peretz, Efraim Idelevich, Sharon Pelles-Avraham, Amichay Meirovitz, Arie Figer, Kenneth Russell, Andreas Voss, Addie Dvir, Lior Soussan-Gutman, Ayala Hubert
BACKGROUND: Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care. OBJECTIVE: To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel. PATIENTS AND METHODS: This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy...
January 20, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29302770/modulating-tumor-immunology-by-inhibiting-indoleamine-2-3-dioxygenase-ido-recent-developments-and-first-clinical-experiences
#19
Diwakar Davar, Nathan Bahary
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the first rate-limiting step in the oxidative metabolism of compounds containing indole rings, including the transformation of the essential amino acid L-tryptophan to N-formyl-L-kynurenine. Through direct and indirect means, IDO exerts both tolerogenic and pro-inflammatory effects and has a profound immunoregulatory role in the tumor microenvironment. Although the role of IDO in mediating peripheral acquired immunologic tolerance has been known for some time, its role in tumorigenesis and the subversion of anti-tumor immunity have only recently been appreciated...
April 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29243205/correction-to-a-phase-ii-study-evaluating-combined-neoadjuvant-cetuximab-and-chemotherapy-followed-by-chemoradiotherapy-and-concomitant-cetuximab-in-locoregional-oesophageal-cancer-patients
#20
Maria Alsina, Fernando Rivera, Francisco Javier Ramos, Maica Galán, Rafael López, Pilar García-Alfonso, José Enrique Alés-Martinez, Bernardo Queralt, Antonio Antón, Alfredo Carrato, Cristina Grávalos, Maria José Méndez-Vidal, Carlos López, Inmaculada Ruiz de Mena, Josep Tabernero, Jordi Giralt, Enrique Aranda
Errors were subsequently identified in the article and the following corrections should be noted.
February 2018: Targeted Oncology
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