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Targeted therapies oncology

Gaia Griguolo, Stephane Pouderoux, Maria Vittoria Dieci, William Jacot, Céline Bourgier, Federica Miglietta, Nelly Firmin, Pierfranco Conte, Marie Viala, Valentina Guarneri, Amélie Darlix
BACKGROUND: Breast cancer (BC) is one of the solid tumors most commonly associated with leptomeningeal disease (LMD). LMD carries a devastating prognosis; however, disease presentation and prognostic factors are uncertain. SUBJECTS, MATERIALS, AND METHODS: In order to describe patient characteristics, treatment patterns, and factors associated with survival in a contemporary multicentric cohort, 153 consecutive BC patients diagnosed with LMD at two European institutions (2002-2017) were included...
August 17, 2018: Oncologist
Stanisław Kwiatkowski, Bartosz Knap, Dawid Przystupski, Jolanta Saczko, Ewa Kędzierska, Karolina Knap-Czop, Jolanta Kotlińska, Olga Michel, Krzysztof Kotowski, Julita Kulbacka
Photodynamic therapy (PDT) is a modern and non-invasive form of therapy, used in the treatment of non-oncological diseases as well as cancers of various types and locations. It is based on the local or systemic application of a photosensitive compound - the photosensitizer, which is accumulated in pathological tissues. The photosensitizer molecules absorb the light of the appropriate wavelength, initiating the activation processes leading to the selective destruction of the inappropriate cells. The photocytotoxic reactions occur only within the pathological tissues, in the area of photosensitizer distribution, enabling selective destruction...
July 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Kai Joachim Borm, Julia Voppichler, Mathias Düsberg, Markus Oechsner, Tibor Vag, Wolfgang Weber, Stephanie Elisabeth Combs, Marciana Nona Duma
PURPOSE: The aim of this study was to localize loco-regional lymph node metastases using positron emission tomography with fluorine 18 fluorodeoxyglucose/computed tomography (FDG-PET/CT) datasets in a large cohort of patients and to evaluate the existing Radiation Therapy Oncology Group (RTOG) clinical target volume (CTV) and the European SocieTy for Radiotherapy & Oncology (ESTRO) CTV contouring guidelines. METHODS: 235 patients with 580 FDG/PET-CT positive loco-regional lymph node metastases were included in our analysis...
August 14, 2018: International Journal of Radiation Oncology, Biology, Physics
Isabel Sousa, Filipa Rodrigues, Hugo Prazeres, Raquel T Lima, Paula Soares
Liposomal therapies opened the chapter of nanomedicine, in 1995, with the approval of liposomal doxorubicin (Doxil® ) for the treatment of numerous types of cancer. For the first time, liposomes permitted the employment of potent chemotherapeutic agents with improved pharmacokinetic and pharmacodynamic profiles, with less undesired side effects. Liposomal therapies allow the drug encapsulation and more selective delivery in the tumor bed, particularly due to the enhanced permeation and retention effect. These unique characteristics explain why liposomal therapies are being increasingly considered as alternatives in cancer therapy and represent an important research field with the recent approval for clinical use and emergent formulations in clinical trials...
August 16, 2018: Cancer Chemotherapy and Pharmacology
Paula Cramer, Julia von Tresckow, Jasmin Bahlo, Sandra Robrecht, Petra Langerbeins, Othman Al-Sawaf, Anja Engelke, Anna-Maria Fink, Kirsten Fischer, Eugen Tausch, Till Seiler, Ludwig Fischer von Weikersthal, Holger Hebart, Karl-Anton Kreuzer, Sebastian Böttcher, Matthias Ritgen, Michael Kneba, Clemens-Martin Wendtner, Stephan Stilgenbauer, Barbara Eichhorst, Michael Hallek
BACKGROUND: Targeted agents such as the type II anti-CD20 antibody obinutuzumab and the B-cell lymphoma-2 antagonist venetoclax have shown impressive therapeutic activity in chronic lymphocytic leukaemia. The CLL2-BAG trial was initiated to investigate the combination of these two agents in patients with chronic lymphocytic leukaemia. METHODS: In this ongoing multicentre, open-label, investigator-initiated phase 2 trial, patients (aged ≥18 years) with chronic lymphocytic leukaemia requiring treatment according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at 16 sites in Germany...
August 13, 2018: Lancet Oncology
Adam J Olszewski, Stacie B Dusetzina, Amal N Trivedi, Amy J Davidoff
Purpose Novel parenteral (bortezomib) and oral (lenalidomide) therapies have improved survival in myeloma, but the standard Medicare benefit covers only parenteral drugs. We examined the association between prescription drug coverage, receipt of therapy, and survival among Medicare beneficiaries with myeloma. Methods Using SEER-Medicare data, we identified enrollment in a Medicare Part D plan (PDP) or other creditable prescription drug coverage (OCC) among 9,755 beneficiaries who were diagnosed with myeloma in 2006 to 2011...
August 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Christian Antonio Tuwahatu, Chi Chung Yeung, Yun Wah Lam, Vellaisamy Arul Lenus Roy
The development of polymeric materials as drug delivery systems has advanced from systems that rely on classical passive targeting to carriers that can sustain the precisely controlled release of payloads upon physicochemical triggers in desired microenvironment. Molecularly imprinted polymers (MIP), materials designed to capture specific molecules based on their molecular shape and charge distribution, are attractive candidates for fulfilling these purposes. In particular, drug-imprinted polymers coupled with active targeting mechanisms have been explored as potential drug delivery systems...
August 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Rodrigo Toledo, Camilo Jimenez
Inactivating mutations of the succinate dehydrogenase subunit B ( SDHB ) gene and the subsequent stabilization and activation of the hypoxia-inducible factor 2-alpha (HIF2α) unit are recognized hallmarks associated with the development of metastatic pheochromocytomas and paragangliomas (MPPG). Despite this discovery, the development of systemic therapies for patients with MPPG has been very slow. The rarity of the disease, the lack of preclinical animal models, and the impracticable development of large clinical trials has hindered the therapeutic progress for MPPG...
2018: F1000Research
Kevin M Sullivan, Heidi L Kenerson, Venu G Pillarisetty, Kimberly J Riehle, Raymond S Yeung
With the widespread adoption of molecular profiling in clinical oncology practice, many physicians are faced with making therapeutic decisions based upon isolated genomic alterations. For example, epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are effective in EGFR-mutant non-small cell lung cancers (NSCLC) while anti-EGFR monoclonal antibodies are ineffective in Ras-mutant colorectal cancers. The matching of mutations with drugs aimed at their respective gene products represents the current state of "precision" oncology...
July 2018: Annals of Translational Medicine
Roger K C Ngan
Hormone therapy, rather than chemotherapy, is recommended for hormone-receptor positive (HR+), human epidermal receptor 2 negative (HER2-) advanced or metastatic breast cancer (A/MBC) according to the European Society of Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines, unless in visceral crisis in which chemotherapy is indicated. Hormonal monotherapy of selective estrogen receptor modulator (SERM) or selective estrogen receptor down-regulator (SERD), aromatase inhibitor (AI), or their combination as doublets, used to be the mainstay options as first-line (1L) therapy for most patients...
July 2018: Annals of Translational Medicine
Joan Carles, Daniel Castellano, María-José Méndez-Vidal, Begoña Mellado, María-Isabel Saez, Aránzazu González Del Alba, José-Luis Perez-Gracia, José Jimenez, Cristina Suárez, Juan M Sepúlveda, Ray Manneh, Ignacio Porras, Cristina López, Rafael Morales-Barrera, José-Ángel Arranz
INTRODUCTION: Although increasing numbers of therapies with proven survival benefits have become available for metastatic castration-resistant prostate cancer (mCRPC), including radium-223, there is still a need for reliable biomarkers that provide information about clinically meaningful outcomes and treatment responses. MATERIALS AND METHODS: This study was a translational study that was conducted prospectively by the Spanish Oncology Genito-Urinary Group and included 45 patients with histologically confirmed mCRPC who were treated with radium-223...
July 21, 2018: Clinical Genitourinary Cancer
Paul Russell Roberts, Ashesh B Jani, Satyaseelan Packianathan, Ashley Albert, Rahul Bhandari, Srinivasan Vijayakumar
For 2018, the American Cancer Society estimated that there would be approximately 1.7 million new diagnoses of cancer and about 609,640 cancer-related deaths in the United States. By 2030 these numbers are anticipated to exceed a staggering 21 million annual diagnoses and 13 million cancer-related deaths. The three primary therapeutic modalities for cancer treatments are surgery, chemotherapy, and radiation therapy. Individually or in combination, these treatment modalities have provided and continue to provide curative and palliative care to the myriad victims of cancer...
August 13, 2018: Radiation Oncology
Ricardo Vianna de Carvalho, Monica Cristina Souza, Cíntia Silva Dos Santos, Rondinele Santos da Silva, Ana Luiza de Mattos-Guaraldi
Bloodstream and venous catheter-related corynebacterial infections in paediatric patients with haematological cancer were investigated from January 2003 to December 2014 at the Brazilian National Cancer Institute in Rio de Janeiro, Brazil. We observed that during cancer treatment, invasive corynebacterial infections occurred independent of certain factors, such as age and gender, underlying diseases and neutropenia. These infections were ssscaused by Corynebacterium amycolatum and other non-diphtherial corynebacteria...
August 10, 2018: Brazilian Journal of Infectious Diseases
Akbar N Ashrafi, Alessandro Tafuri, Giovanni E Cacciamani, Daniel Park, Andre L de Castro Abreu, Inderbir S Gill
PURPOSE OF REVIEW: To present a perspective on the current status and future directions of focal therapy for prostate cancer (PCa). RECENT FINDINGS: Focal therapy for localized PCa is a rapidly evolving field. Various recent concepts - the index lesion driving prognosis, the enhanced detection of clinically significant PCa using multiparametric MRI and targeted biopsy, improved risk-stratification using novel blood/tissue biomarkers, the recognition that reducing radical treatment-related morbidity (along with reducing pathologic progression) is a clinically meaningful end-point - have all led to a growing interest in focal therapy...
August 10, 2018: Current Opinion in Urology
Takumi Shiraishi, Osamu Ukimura
PURPOSE OF REVIEW: With the increasing incidence of low-to-intermediate risk of prostate cancer (PCa) by the introduction of prostate-specific antigen (PSA) screening, focal therapy has become one of the promising treatment options in the world. In Asia, same movement are occurring using several technologies including cryoablation, high-intensity focused ultrasound, brachytherapy and irreversible electroporation. However, these are still not common strategies to treat organ-confined PCa...
August 10, 2018: Current Opinion in Urology
Megumi Uto, Takashi Mizowaki, Kengo Ogura, Nobutaka Mukumoto, Tomohiro Katagiri, Keiichi Takehana, Masahiro Hiraoka
Mono-isocentric volumetric-modulated arc therapy (VMAT) can be used to treat multiple brain metastases. It remains unknown whether mono-isocentric VMAT can improve the dose distribution compared with dual-isocentric dynamic conformal arc therapy (DCAT), especially for two brain metastases. We compared the dose distribution between dual-isocentric DCAT and mono-isocentric VMAT for two large brain metastases, and analyzed the relationship between the distance between the two targets and the difference in dose distribution...
August 9, 2018: Journal of Radiation Research
Erlinda M Gordon, Joshua R Ravicz, Seiya Liu, Sant P Chawla, Frederick L Hall
Basic research in genetics, biochemistry and cell biology has identified the executive enzymes and protein kinase activities that regulate the cell division cycle of all eukaryotic organisms, thereby elucidating the importance of site-specific protein phosphorylation events that govern cell cycle progression. Research in cancer genomics and virology has provided meaningful links to mammalian checkpoint control elements with the characterization of growth-promoting proto-oncogenes encoding c-Myc, Mdm2, cyclins A, D1 and G1, and opposing tumor suppressor proteins, such as p53, pRb, p16INK4A and p21WAF1 , which are commonly dysregulated in cancer...
August 2018: Molecular and Clinical Oncology
Mehreen Ali, Tero Aittokallio
In-depth modeling of the complex interplay among multiple omics data measured from cancer cell lines or patient tumors is providing new opportunities toward identification of tailored therapies for individual cancer patients. Supervised machine learning algorithms are increasingly being applied to the omics profiles as they enable integrative analyses among the high-dimensional data sets, as well as personalized predictions of therapy responses using multi-omics panels of response-predictive biomarkers identified through feature selection and cross-validation...
August 10, 2018: Biophysical Reviews
Christian Rolfo, Paolo Manca, Roberto Salgado, Peter Van Dam, Amelie Dendooven, Andreia Machado Coelho, Jose Ferri Gandia, Annemie Rutten, Willem Lybaert, Joanna Vermeij, Thomas Gevaert, Christine Weyn, Anneke Lefebure, Sofie Metsu, Steven Van Laere, Marc Peeters, Patrick Pauwels
Background: The complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report aims to analyse the experience of our MTB in the implementation of personalised medicine in a cancer network. Materials and methods: Patients diagnosed with solid tumours progressing to standard treatments were referred to our Phase I unit...
2018: ESMO Open
Dan-Dan Xiong, Yi-Wu Dang, Peng Lin, Dong-Yue Wen, Rong-Quan He, Dian-Zhong Luo, Zhen-Bo Feng, Gang Chen
BACKGROUND: Circular RNAs (circRNAs) have received increasing attention in human tumor research. However, there are still a large number of unknown circRNAs that need to be deciphered. The aim of this study is to unearth novel circRNAs as well as their action mechanisms in hepatocellular carcinoma (HCC). METHODS: A combinative strategy of big data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology was employed to dig HCC-related circRNAs and to explore their potential action mechanisms...
August 9, 2018: Journal of Translational Medicine
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