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Targeted Oncology

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https://www.readbyqxmd.com/read/28712059/a-combination-of-testosterone-and-white-blood-cell-count-as-a-predictive-factor-of-overall-survival-in-localized-prostate-cancer
#1
Daniel Taussky, Denis Souliéres, Laurent Azoulay, Hui Yin, Houda Bahig, Jean-Paul Bahary, Guila Delouya
BACKGROUND: It has been shown that neutrophil count or an elevated neutrophil-to-lymphocyte ratio (NLR) as well as testosterone levels are separately associated with increased mortality in patients with localized prostate cancer. OBJECTIVE: We tested a combination of testosterone levels and white blood cell (WBC) counts to predict overall survival (OS) in a prospective cohort of patients treated with radiotherapy for localized prostate cancer. PATIENTS AND METHODS: The 381 patients included in this study were prospectively enrolled in phase 2 or 3 studies...
July 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28710746/osimertinib-a-review-in-t790m-positive-advanced-non-small-cell-lung-cancer
#2
REVIEW
Yvette N Lamb, Lesley J Scott
Osimertinib (Tagrisso™) is an oral, CNS-active, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets EGFR TKI-sensitizing mutations and, crucially, the T790M mutation that often underlies acquired resistance to EGFR TKI therapy. Osimertinib has been approved in numerous countries for use in patients with T790M-positive advanced NSCLC. In the pivotal, international AURA3 trial in patients with T790M-positive advanced NSCLC who had disease progression after EGFR TKI therapy, osimertinib treatment significantly prolonged progression-free survival (PFS; primary endpoint) compared with platinum-pemetrexed therapy at the time of the primary analysis...
July 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28710745/the-pan-bcl2-inhibitor-at101-activates-the-intrinsic-apoptotic-pathway-and-causes-dna-damage-in-acute-myeloid-leukemia-stem-like-cells
#3
Leisi Zhang, Yong Zhou, Kai Chen, Pengcheng Shi, Yin Li, Manman Deng, Zhiwu Jiang, Xiangmeng Wang, Peng Li, Bing Xu
BACKGROUND: Leukemia stem cells (LSCs) are considered to be the cause of treatment failure and relapse in acute myeloid leukemia (AML). Overexpression of the Bcl-2 family of anti-apoptotic proteins such as Bcl-2, Bcl-xl, and Mcl-1 accounts for survival and self-renewal of LSCs. AT101 binds to the BH3 motif of all Bcl-2 family anti-apoptotic proteins and demonstrates anti-tumor activity in multiple types of tumor. Thus, we hypothesized that this agent might have the potential to deplete LSCs...
July 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28702806/efficacy-and-safety-of-nintedanib-plus-docetaxel-in-patients-with-advanced-lung-adenocarcinoma-complementary-and-exploratory-analyses-of-the-phase-iii-lume-lung-1-study
#4
Maya Gottfried, Jaafar Bennouna, Igor Bondarenko, Jean-Yves Douillard, David F Heigener, Maciej Krzakowski, Anders Mellemgaard, Silvia Novello, Sergei Orlov, Yvonne Summers, Joachim von Pawel, Julia Stöhr, Rolf Kaiser, Martin Reck
BACKGROUND: Nintedanib is a triple angiokinase inhibitor approved with docetaxel for adenocarcinoma non-small cell lung cancer after first-line chemotherapy (FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all adenocarcinoma patients and those with time from start of FLT (TSFLT) <9 months. OBJECTIVE: This study sought to extend analyses from the LUME-Lung 1 study, specifically for adenocarcinoma patients, to explore the impact of clinically relevant characteristics on outcomes such as time to progression after FLT...
July 12, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28699084/egfr-mutation-testing-of-non-squamous-nsclc-impact-and-uptake-during-implementation-of-testing-guidelines-in-a-population-based-registry-cohort-from-northern-new-zealand
#5
Mark McKeage, Mark Elwood, Sandar Tin Tin, Prashannata Khwaounjoo, Phyu Aye, Angie Li, Karen Sheath, Phillip Shepherd, George Laking, Nicola Kingston, Christopher Lewis, Donald Love
BACKGROUND: Since 2013, clinical practice guidelines recommend EGFR mutation testing of non-squamous NSCLC to select advanced-stage patients for first-line treatment using EGFR-TKIs. OBJECTIVE: We aimed to determine population-based trends in the real-world uptake and impact in routine practice of these recently updated testing guidelines. PATIENTS AND METHODS: A population-based observational study was conducted of notifications to the New Zealand Cancer Registry of patients eligible for EGFR testing diagnosed in northern New Zealand between January 2010 and April 2014...
July 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28685321/targeting-fgfr-in-squamous-cell-carcinoma-of-the-lung
#6
Neda Hashemi-Sadraei, Nasser Hanna
Unlike for adenocarcinomas of the lung, no molecular targeted therapies have yet been developed for squamous cell lung cancers, because targetable oncogenic aberrations are scarce in this tumor type. Recent discoveries have established that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in cancer development by supporting tumor angiogenesis and cancer cell proliferation via different mechanisms. Through comprehensive genomic studies, aberrations in the FGF pathway have been identified in various tumor types, including squamous cell lung cancer, making FGF receptor (FGFR) a potentially druggable target in this malignancy...
July 6, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28669023/pooled-analysis-of-clinical-outcome-of-patients-with-chemorefractory-metastatic-colorectal-cancer-treated-within-phase-i-ii-clinical-studies-based-on-individual-biomarkers-of-susceptibility-a-single-institution-experience
#7
Andrea Sartore-Bianchi, Alessio Amatu, Erica Bonazzina, Stefano Stabile, Laura Giannetta, Giulio Cerea, Ilaria Schiavetto, Katia Bencardino, Chiara Funaioli, Riccardo Ricotta, Tiziana Cipani, Michele Schirru, Valentina Gambi, Laura Palmeri, Giulia Carlo-Stella, Francesca Rusconi, Sara Di Bella, Giovanni Burrafato, Andrea Cassingena, Emanuele Valtorta, Calogero Lauricella, Federica Pazzi, Alessandra Gambaro, Silvia Ghezzi, Giovanna Marrapese, Emiliana Tarenzi, Silvio Veronese, Mauro Truini, Angelo Vanzulli, Salvatore Siena
BACKGROUND: Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value. OBJECTIVE: We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s)...
July 1, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28664387/overview-of-cancer-stem-cells-and-stemness-for-community-oncologists
#8
Justin D Lathia, Huiping Liu
Advances in cancer research in the past have led to an evolving understanding of cancer pathogenesis and the development of novel drugs that significantly improve patient outcomes. However, many patients still encounter treatment resistance, recurrence, or metastasis and eventually die from progressing disease. Experimental evidence indicates that a subpopulation of cancer cells, called cancer stem cells (CSCs), possess "stemness" properties similar to normal stem cells, including self-renewal, differentiation, and proliferative potential...
June 30, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28664386/novel-therapies-for-acute-myeloid-leukemia-are-we-finally-breaking-the-deadlock
#9
REVIEW
Maximilian Stahl, Benjamin Y Lu, Tae Kon Kim, Amer M Zeidan
Acute myeloid leukemia (AML) is one of the best studied malignancies, and significant progress has been made in understanding the clinical implications of its disease biology. Unfortunately, drug development has not kept pace, as the '7+3' induction regimen remains the standard of care for patients fit for intensive therapy 40 years after its first use. Temporal improvements in overall survival were mostly confined to younger patients and driven by improvements in supportive care and use of hematopoietic stem cell transplantation...
June 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28664385/pazopanib-a-review-in-advanced-renal-cell-carcinoma
#10
REVIEW
James E Frampton
Pazopanib (Votrient®), an orally administered multi-targeted tyrosine kinase inhibitor that predominantly inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet-derived growth factor receptor-α and -β, and the stem cell factor receptor c-Kit, is approved in the EU, the USA and other countries for the treatment of advanced renal cell carcinoma (RCC). In randomized controlled trials in patients with advanced, predominantly clear-cell RCC, pazopanib significantly improved progression-free survival (PFS) compared with placebo in both treatment-naïve and cytokine-pretreated patients and, as a first-line therapy, was noninferior to intermittent sunitinib with respect to PFS...
June 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28660423/ixazomib-a-review-in-relapsed-and-or-refractory-multiple-myeloma
#11
REVIEW
Zaina T Al-Salama, Karly P Garnock-Jones, Lesley J Scott
The oral proteasome inhibitor ixazomib (Ninlaro(®)) is approved in the USA, EU and Japan in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. In adults with relapsed and/or refractory MM who had received one to three prior therapies, progression-free survival (PFS) was significantly prolonged in patients who received the ixazomib- versus placebo-based triple therapy in the pivotal, global TOURMALINE-MM1 trial and its regional expansion (China continuation study)...
June 28, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28653295/targeting-the-wnt-pathway-in-cancer-a-review-of-novel-therapeutics
#12
Roya Tabatabai, Yuliya Linhares, David Bolos, Monica Mita, Alain Mita
Wnt signaling is an evolutionarily conserved pathway that controls cell-to-cell interactions during embryogenesis. In adults, Wnt signaling plays a role in tissue homeostasis in almost every organ system. Aberrations within this pathway are implicated in a spectrum of human diseases. A variety of perturbations have been described in both solid and hematologic malignancies, lending way to Wnt signaling as a target for anti-cancer therapy. Of particular interest is the role of Wnt signaling in the development and maintenance of cancer stem cells, a rare population of cells that are able to maintain a tumor via self-renewal and thought to be more resistant to chemotherapy than bulk tumor cells...
June 26, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28634872/predictive-markers-of-response-to-everolimus-and-sunitinib-in-neuroendocrine-tumors
#13
Diana Martins, Francesca Spada, Ioana Lambrescu, Manila Rubino, Chiara Cella, Bianca Gibelli, Chiara Grana, Dario Ribero, Emilio Bertani, Davide Ravizza, Guido Bonomo, Luigi Funicelli, Eleonora Pisa, Dario Zerini, Nicola Fazio
Neuroendocrine tumors (NETs) represent a large and heterogeneous group of malignancies with various biological and clinical characteristics, depending on the site of origin and the grade of tumor proliferation. In NETs, as in other cancer types, molecularly targeted therapies have radically changed the therapeutic landscape. Recently two targeted agents, the mammalian target of rapamycin inhibitor everolimus and the tyrosine kinase inhibitor sunitinib, have both demonstrated significantly prolonged progression free survival in patients with advanced pancreatic NETs...
June 21, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28624922/targeting-the-pd-1-pd-l1-immune-checkpoint-in-egfr-mutated-or-alk-translocated-non-small-cell-lung-cancer
#14
Olivier Bylicki, Nicolas Paleiron, Jacques Margery, Florian Guisier, Alain Vergnenegre, Gilles Robinet, Jean-Bernard Auliac, Radj Gervais, Christos Chouaid
Immune checkpoint inhibitors, notably antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), have modified the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Several PD-1/PD-L1 inhibitors have been approved by health authorities for this indication and others are in clinical development. However, only a subset of patients truly benefits from these agents. For patients with mutated EGFR or translocated ALK NSCLC, for whom an immune checkpoint inhibitor can be prescribed after progression on tyrosine kinase inhibitors and chemotherapy, information is scarce and sometimes contradictory...
June 18, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28624921/lung-adenocarcinoma-survival-in-egfr-mutated-african-caribbean-patients-a-multicenter-study-in-the-french-west-indies
#15
Nicolas Leduc, Vincent Atallah, Moustapha Agossou, Vincent Vinh-Hung, Mathieu Orre, Paul Sargos, Vincent Molinie
BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Shorter survival has been repeatedly reported for patients of African ancestry. Multivariate analysis demonstrated that this gap could be a consequence of socio-economic disparities instead of genetic specificities. However, those results were obtained in a pre-targeted therapies era and the effect of tyrosine kinase inhibitors targeting EGFR are not known in this population. OBJECTIVE: In this French West Indies study, we report overall survival (OS) in a frequently mutated population treated for lung adenocarcinoma within an equal-access healthcare system...
June 18, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28620691/biomarkers-for-the-management-of-castration-resistant-prostate-cancer-we-are-not-there-yet
#16
Daniel P Petrylak, E David Crawford
In recent years, there has been a marked increase in the number of approved therapies that increase survival of patients with castration-resistant prostate cancer. Current treatment guidelines provide therapeutic management recommendations, but these are primarily based on clinical factors such as performance status or site of metastasis (bone vs. visceral), and not on underlying molecular or cellular features of disease that may predict response. The ability to tailor treatment based on molecular or cellular features of disease could potentially reduce the occurrence of unnecessary side effects and ineffective treatments, and thereby reduce both direct and indirect medical costs...
June 16, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28620690/acquired-resistance-to-erlotinib-in-egfr-mutation-positive-lung-adenocarcinoma-among-hispanics-clicap
#17
Andrés F Cardona, Oscar Arrieta, Martín Ignacio Zapata, Leonardo Rojas, Beatriz Wills, Noemí Reguart, Niki Karachaliou, Hernán Carranza, Carlos Vargas, Jorge Otero, Pilar Archila, Claudio Martín, Luis Corrales, Mauricio Cuello, Carlos Ortiz, Luis E Pino, Rafael Rosell, Zyanya Lucia Zatarain-Barrón
BACKGROUND: Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. PATIENTS AND METHODS: EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015...
June 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28589492/a-phase-1-study-of-ly2874455-an-oral-selective-pan-fgfr-inhibitor-in-patients-with-advanced-cancer
#18
Michael Michael, Yung-Jue Bang, Young Suk Park, Yoon-Koo Kang, Tae Min Kim, Oday Hamid, Donald Thornton, Sonya C Tate, Eyas Raddad, Jeanne Tie
BACKGROUND: We report here a phase 1 study of LY2874455, a potent oral selective pan-fibroblast growth factor receptor (FGFR) inhibitor. OBJECTIVE: The primary objective was to determine the recommended phase 2 dosing (RP2D). Secondary objectives included determining toxicity, antitumor activity, pharmacokinetics (PK), and pharmacodynamic (PD) properties of LY2874455. PATIENTS AND METHODS: This study comprised two parts: (a) dose escalation with 3 + 3 cohorts in patients with solid tumors and (b) dose-expansion cohorts in patients with gastric cancer (GC) and non-small cell lung cancer (NSCLC)...
June 6, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28589491/synthesis-and-characterization-of-novel-bmi1-inhibitors-targeting-cellular-self-renewal-in-hepatocellular-carcinoma
#19
Monica Bartucci, Mohamed S Hussein, Eric Huselid, Kathleen Flaherty, Michele Patrizii, Saurabh V Laddha, Cindy Kui, Rachel A Bigos, John A Gilleran, Mervat M S El Ansary, Mona A M Awad, S David Kimball, David J Augeri, Hatem E Sabaawy
BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most lethal cancers worldwide due to therapy resistance and disease recurrence. Tumor relapse following treatment could be driven by the persistence of liver cancer stem-like cells (CSCs). The protein BMI1 is a member of the polycomb epigenetic factors governing cellular self-renewal, proliferation, and stemness maintenance. BMI1 expression also correlates with poor patient survival in various cancer types. OBJECTIVE: We aimed to elucidate the extent to which BMI1 can be used as a potential therapeutic target for CSC eradication in HCC...
June 6, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28580507/retrospective-evaluation-of-thromboembolism-risk-in-ovarian-cancer-patients-treated-with-bevacizumab
#20
Anna Kuk, Magdalena Magnowska, Wiktor Suchy, Joanna Swierczynska, Mikolaj Piotr Zaborowski, Michal Gaca, Ewa Nowak-Markwitz
BACKGROUND: Bevacizumab is used in addition to standard, platinum-based chemotherapy to treat advanced-stage ovarian cancer patients. Thrombosis is a well-documented adverse effect of bevacizumab. OBJECTIVE: The aim of this study was to identify predictive parameters for thromboembolic events in ovarian cancer patients and to explain how bevacizumab increases the risk of these events. PATIENTS AND METHODS: Fifty-seven FIGO stage III ovarian cancer patients who underwent cytoreductive surgery and chemotherapy were identified and included in this retrospective study...
June 4, 2017: Targeted Oncology
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