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Targeted Oncology

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https://www.readbyqxmd.com/read/29470785/the-abscopal-effect-in-the-era-of-cancer-immunotherapy-a-spontaneous-synergism-boosting-anti-tumor-immunity
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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...
January 4, 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
#11
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.
December 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29235062/retreatment-with-vismodegib-after-progression-in-advanced-basal-cell-carcinoma-first-time-report-of-a-single-institution-experience
#12
REVIEW
Salvatore Alfieri, Cristiana Bergamini, Roberta Granata, Laura Locati, Lisa Licitra, Paolo Bossi
Retreatment with vismodegib in advanced basal cell carcinoma (BCC) patients who previously discontinued the drug due to disease progression (PD) has not been reported yet. The objective of our report is to determine whether vismodegib is still active when used in BCC patients who progressed during a first vismodegib course (FVC). We conducted a retrospective study on six advanced BCC patients enrolled in a clinical trial (STEVIE, NCT01367665) who discontinued vismodegib due to PD and were then retreated with the same drug...
December 12, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29230672/the-role-of-b-cell-maturation-antigen-in-the-biology-and-management-of-and-as-a-potential-therapeutic-target-in-multiple-myeloma
#13
Eric Sanchez, Emily J Smith, Moryel A Yashar, Saurabh Patil, Mingjie Li, Autumn L Porter, Edward J Tanenbaum, Remy E Schlossberg, Camilia M Soof, Tara Hekmati, George Tang, Cathy S Wang, Haiming Chen, James R Berenson
B-cell maturation antigen (BCMA) was originally identified as a cell membrane receptor, expressed exclusively on late stage B-cells and plasma cells (PCs). Investigations of BCMA as a target for therapeutic intervention in multiple myeloma (MM) were initiated in 2007, using cSG1 as a naked antibody (Ab) as well as an Ab-drug conjugate (ADC) targeting BCMA, ultimately leading to ongoing clinical studies for previously treated MM patients. Since then, multiple companies have developed anti-BCMA-directed ADCs...
December 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29230671/incorporating-dna-methyltransferase-inhibitors-dnmtis-in-the-treatment-of-genitourinary-malignancies-a-systematic-review
#14
Michal Chovanec, Fadi Taza, Maitri Kalra, Noah Hahn, Kenneth P Nephew, Michael J Spinella, Costantine Albany
Inhibition of DNA methyltransferases (DNMTs) has emerged as a novel treatment strategy in solid tumors. Aberrant hypermethylation in promoters of critical tumor suppressor genes is the basis for the idea that treatment with hypomethylating agents may lead to the restoration of a "normal" epigenome and produce clinically meaningful therapeutic outcomes. The aim of this review article is to summarize the current state of knowledge of DNMT inhibitors in the treatment of genitourinary malignancies. The efficacy of these agents in genitourinary malignancies was reported in a number of studies and suggests a role of induced DNA hypomethylation in overcoming resistance to conventional cytotoxic treatments...
December 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29218624/motivation-for-launching-a-cancer-metastasis-inhibition-cmi-program
#15
REVIEW
Jill M Pulley, Rebecca N Jerome, Martin L Ogletree, Gordon R Bernard, Robert R Lavieri, Nicole M Zaleski, Charles C Hong, Jana K Shirey-Rice, Carlos L Arteaga, Ingrid A Mayer, Kenneth J Holroyd, Rebecca S Cook
Metastatic cancers impose significant burdens on patients, affecting quality of life, morbidity, and mortality. Even during remission, microscopic metastases can lurk, but few therapies directly target tumor cell metastasis. Agents that interfere with this process would represent a new paradigm in cancer management, changing the 'waiting game' into a time of active prevention. These therapies could take multiple forms based on the pathways involved in the metastatic process. For example, a phenome-wide association study showed that a single nucleotide polymorphism in the gene TBXA2R is associated with increased metastasis in multiple primary cancers (P = 0...
December 7, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29218623/early-metabolic-change-after-induction-chemotherapy-predicts-histologic-response-and-prognosis-in-patients-with-esophageal-cancer-secondary-analysis-of-a-randomized-trial
#16
Kazuto Harada, Xuemei Wang, Yusuke Shimodaira, Tara Sagebiel, Manoop S Bhutani, Jeffrey H Lee, Brian Weston, Elena Elimova, Quan Lin, Fatemeh G Amlashi, Dilsa Mizrak Kaya, Anthony Lopez, Mariela A Blum Murphy, Jack A Roth, Stephen G Swisher, Heath D Skinner, Wayne L Hofstetter, Jane E Rogers, Irene Thomas, Dipen M Maru, Ritsuko Komaki, Garrett Walsh, Jaffer A Ajani
BACKGROUND: Early metabolic response after preoperative induction chemotherapy (IC) appears to predict histologic response and prognosis in esophageal cancer (EC), but the usefulness of this approach needs further development. OBJECTIVE: We evaluated metabolic response after one cycle of IC using positron emission tomography (PET) to correlate PET response and outcomes. PATIENTS AND METHODS: We retrospectively analyzed PET data from a randomized phase 2 trial (NCT00525915) of chemoradiation and surgery with or without IC for the treatment of EC...
December 7, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29218622/inhibiting-cdk-in-cancer-therapy-current-evidence-and-future-directions
#17
REVIEW
Smruthi Vijayaraghavan, Stacy Moulder, Khandan Keyomarsi, Rachel M Layman
Cell cycle dysregulation is a hallmark of all cancers, resulting in uncontrolled proliferation. Cyclin dependent kinases (CDKs), a family of proteins that are involved in the regulation of the cell cycle, are frequently overexpressed or mutated in cancer. Hence, CDK-inhibiting drugs have been developed and evaluated as cancer therapeutics. Clinical trials have shown CDK4/6 inhibitors (CDK4/6i) to be relatively safe and effective, and these are now standard of care treatment for advanced hormone receptor positive breast cancer...
December 7, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29188408/phase-ib-trial-of-the-anti-cancer-stem-cell-dll4-binding-agent-demcizumab-with-pemetrexed-and-carboplatin-as-first-line-treatment-of-metastatic-non-squamous-nsclc
#18
Mark J McKeage, Dusan Kotasek, Ben Markman, Manuel Hidalgo, Michael J Millward, Michael B Jameson, Dean L Harris, Robert J Stagg, Ann M Kapoun, Lu Xu, Brett G M Hughes
BACKGROUND: Delta-like ligand 4-Notch (DLL4-Notch) signaling contributes to the maintenance of chemotherapy-resistant cancer stem cells and tumor vasculature. OBJECTIVE: This phase IB trial of demcizumab, an IgG2 humanized monoclonal antibody directed against DLL4, was undertaken to determine its maximum tolerated dose, safety, immunogenicity, preliminary efficacy, pharmacokinetics, and pharmacodynamics, combined with standard chemotherapy. PATIENTS AND METHODS: Forty-six treatment-naive patients with metastatic non-squamous non-small cell lung cancer (NSCLC) were enrolled in this open-label, dose-escalation study using a standard 6 + 6 design...
November 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29143176/the-treatment-landscape-and-new-opportunities-of-molecular-targeted-therapies-in-gastroenteropancreatic-neuroendocrine-tumors
#19
REVIEW
Fabiola Amair-Pinedo, Ignacio Matos, Tamara Saurí, Jorge Hernando, Jaume Capdevila
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms that originate from neuroendocrine stem cells and express both neural and endocrine markers. They are found in almost every organ, and while NENs are mostly associated with slow growth, complications due to the uncontrolled secretion of active peptides, and metastatic disease, may significantly impair the quality of life and can ultimately lead to the death of affected individuals. Expanding knowledge of the genetic, epigenetic, and proteomic landscapes of NENs has led to a better understanding of their molecular pathology and consequently increased treatment options for patients...
December 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29064002/cea-response-and-depth-of-response-dpr-to-predict-clinical-outcomes-of-first-line-cetuximab-treatment-for-metastatic-colorectal-cancer
#20
Yu Sunakawa, Akihito Tsuji, Tadamichi Denda, Yoshihiko Segawa, Yuji Negoro, Ken Shimada, Mitsugu Kochi, Masato Nakamura, Masahito Kotaka, Hiroaki Tanioka, Akinori Takagane, Satoshi Tani, Tatsuro Yamaguchi, Takanori Watanabe, Masahiro Takeuchi, Masashi Fujii, Wataru Ichikawa
BACKGROUND: The decrease in carcinoembryonic antigen (CEA) level is faster and greater during cetuximab treatment than bevacizumab treatment and correlates with prolonged survival in patients with metastatic colorectal cancer (mCRC) who receive cetuximab. OBJECTIVE: We investigated if the degree of change in the CEA value can serve as a diagnostic tool for predicting survival, as well as tumor regression in mCRC patients treated with cetuximab combined regimen as first-line treatment...
December 2017: Targeted Oncology
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