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Targeted Oncology

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https://www.readbyqxmd.com/read/29235062/retreatment-with-vismodegib-after-progression-in-advanced-basal-cell-carcinoma-first-time-report-of-a-single-institution-experience
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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/29177953/phase-ii-study-of-gemcitabine-plus-sirolimus-in-previously-treated-patients-with-advanced-soft-tissue-sarcoma-a-spanish-group-for-research-on-sarcomas-geis-study
#8
Juan Martin-Liberal, Antonio López-Pousa, Javier Martínez-Trufero, Javier Martín-Broto, Ricardo Cubedo, Javier Lavernia, Andrés Redondo, José Antonio López-Martín, Nùria Mulet-Margalef, Xavier Sanjuan, Òscar M Tirado, Xavier Garcia-Del-Muro
BACKGROUND: Gemcitabine plus sirolimus enhances apoptosis in vitro and increases anti-tumor efficacy in vivo in soft-tissue sarcoma (STS) models. OBJECTIVE: The objective of this study was to evaluate the activity and toxicity of the combination of gemcitabine plus sirolimus in patients with STS after failure of standard chemotherapy. PATIENTS AND METHODS: Advanced STS patients, previously treated with doxorubicin and/or ifosfamide, were included in this single-arm phase II study...
November 24, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29143176/the-treatment-landscape-and-new-opportunities-of-molecular-targeted-therapies-in-gastroenteropancreatic-neuroendocrine-tumors
#9
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...
November 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29128908/cetuximab-tpf-radiotherapy-in-oesophageal-cancer
#10
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
BACKGROUND: Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. OBJECTIVE: We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. PATIENTS AND METHODS: Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles...
November 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29116596/antibody-drug-conjugates-for-the-treatment-of-solid-tumors-clinical-experience-and-latest-developments
#11
Aiko Nagayama, Leif W Ellisen, Bruce Chabner, Aditya Bardia
Antibody-drug conjugates (ADCs) are complex immunoconjugates designed to selectively deliver toxic small molecules preferentially to cancer cells. These immunoconjugates consist of a monoclonal antibody - directed to a tumor antigen - and a cytotoxic agent that is conjugated to the antibody via a molecular linker. Following the binding to a specific antigen on the surface of cancer cells, the conjugate is internalized and releases its cytotoxic payload to kill the malignant cell. ADCs that have gained regulatory approval from the US Food and Drug Administration (FDA) include brentuximab vedotin for CD30-positive Hodgkin's lymphoma and trastuzumab emtansine for human epidermal growth factor receptor 2 (HER2)-positive breast cancer...
November 8, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29090377/trastuzumab-in-combination-with-folfiri-in-patients-with-advanced-her2-positive-gastro-esophageal-adenocarcinoma-a-retrospective-multicenter-ageo-study
#12
Aziz Zaanan, Juliette Palle, Emilie Soularue, Florence Leroy, Samy Louafi, David Tougeron, Sylvain Manfredi, Pascal Artru, Astrid Pozet, Julien Taieb
BACKGROUND: Trastuzumab with fluoropyrimidine and cisplatin is the standard first-line treatment in patients with HER2-positive advanced gastro-esophageal adenocarcinoma. However, there are no safety and efficacy data of trastuzumab with FOLFIRI. OBJECTIVE: To evaluate safety and efficacy of FOLFIRI plus trastuzumab in patients with HER2-positive advanced gastro-esophageal adenocarcinoma. PATIENTS AND METHODS: This retrospective multicenter study included all consecutive patients with HER2-positive advanced gastro-esophageal adenocarcinoma treated with FOLFIRI plus trastuzumab between 2012 and 2015...
October 31, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29080944/comment-on-non-small-cell-lung-cancer-nsclc-harboring-alk-translocations-clinical-characteristics-and-management-in-a-real-life-setting-a-french-retrospective-analysis-gfpc-02-14-study
#13
LETTER
https://www.readbyqxmd.com/read/29080943/author-s-reply-to-arnaud-uguen-non-small-cell-lung-cancer-nsclc-harboring-alk-translocations-clinical-characteristics-and-management-in-a-real-life-setting-a-french-retrospective-analysis-gfpc-02-14-study
#14
LETTER
https://www.readbyqxmd.com/read/29067644/targeting-anaplastic-lymphoma-kinase-alk-in-rhabdomyosarcoma-rms-with-the-second-generation-alk-inhibitor-ceritinib
#15
Anke E M van Erp, Melissa H S Hillebrandt-Roeffen, Laurens van Houdt, Emmy D G Fleuren, Winette T A van der Graaf, Yvonne M H Versleijen-Jonkers
BACKGROUND: The receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) has been implicated in the tumorigenesis of rhabdomyosarcoma (RMS). However, the exact role of ALK in RMS is debatable and remains to be elucidated. OBJECTIVE: To determine the in vitro and in vivo effects and mechanism of action of the second-generation ALK inhibitor ceritinib on RMS cell growth. METHODS: Effects of ceritinib on cell proliferation, wound healing, cell cycle, and RTK signaling were determined in alveolar and embryonal rhabdomyosarcoma (ARMS, ERMS)...
October 24, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29067643/a-multi-arm-phase-i-study-of-the-pi3k-mtor-inhibitors-pf-04691502-and-gedatolisib-pf-05212384-plus-irinotecan-or-the-mek-inhibitor-pd-0325901-in-advanced-cancer
#16
Zev A Wainberg, Maria Alsina, Heloisa P Soares, Irene Braña, Carolyn D Britten, Gianluca Del Conte, Patrick Ezeh, Brett Houk, Kenneth A Kern, Stephen Leong, Nuzhat Pathan, Kristen J Pierce, Lillian L Siu, Jennifer Vermette, Josep Tabernero
BACKGROUND: This phase I, four-arm, open-label study (NCT01347866) evaluated the PI3K/mTOR inhibitors PF-04691502 (arms A, B) and gedatolisib (PF-05212384; arms C, D) in combination with the MEK inhibitor PD-0325901 (arm A, D) or irinotecan (arm B, C) in patients with advanced solid tumors. OBJECTIVES: Primary endpoint was dose-limiting toxicity with each combination. Secondary endpoints included safety, pharmacokinetics and preliminary antitumor activity. PATIENTS AND METHODS: Dose escalation followed a 3 + 3 design in arm C and a zone-based design in arm D...
October 24, 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
#17
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...
October 24, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29022151/comparative-safety-of-targeted-therapies-for-metastatic-colorectal-cancer-between-elderly-and-younger-patients-a-study-using-the-international-pharmacovigilance-database
#18
Amandine Gouverneur, Pauline Claraz, Marine Rousset, Mickaël Arnaud, Annie Fourrier-Réglat, Antoine Pariente, Thomas Aparicio, Ghada Miremont-Salamé, Pernelle Noize
BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Post-marketing safety of these agents is understudied, especially in the elderly. OBJECTIVE: This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life. PATIENTS AND METHODS: An extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed...
October 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28815409/insulin-like-growth-factor-igf-pathway-targeting-in-cancer-role-of-the-igf-axis-and-opportunities-for-future-combination-studies
#19
Aaron Simpson, Wilfride Petnga, Valentine M Macaulay, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair...
October 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28803351/dose-and-schedule-selection-of-the-oral-proteasome-inhibitor-ixazomib-in-relapsed-refractory-multiple-myeloma-clinical-and-model-based-analyses
#20
Neeraj Gupta, Huyuan Yang, Michael J Hanley, Steven Zhang, Rachael Liu, Shaji Kumar, Paul G Richardson, Tomas Skacel, Karthik Venkatakrishnan
BACKGROUND: The oral proteasome inhibitor ixazomib has been approved by regulatory authorities around the world, including in the United States and the European Union, for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy, based on the pivotal phase III TOURMALINE-MM1 study. OBJECTIVE: The objective of this study was to quantitatively characterize the benefit-risk profile of ixazomib in relapsed/refractory MM in support of the approved dose and schedule...
October 2017: Targeted Oncology
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