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Current Cancer Drug Targets

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https://www.readbyqxmd.com/read/28201978/multiple-myeloma-and-the-immune-microenvironment
#1
Yawara Kawano, Aldo M Roccaro, Jamil Azzi, Irene M Ghobrial
One of the great advances in the field of cancer therapy in recent years is the emergence of immune therapies. Immune therapies, especially immune checkpoint inhibitors, have shown promising results in pre-clinical models and clinical trials of solid tumors, such as melanoma, breast cancer and lung cancer. Therapeutic strategies targeting the immune microenvironment have also been applied to hematological malignancies such as multiple myeloma (MM), a plasma cell neoplasia characterized by clonal expansion of malignant plasma cells mainly in the bone marrow (BM)...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#2
Klaus Podar, D J├Ąger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28201976/immunomodulatory-drugs-imids-in-multiple-myeloma
#3
Shahzad Raza, Rachael A Safyan, Lentzsch Suzanne
Multiple myeloma (MM) is a plasma cell neoplasm that is incurable with conventional therapy. However, the treatment of MM has dramatically changed since the emergence of immunomodulatory drugs and proteasome inhibitors. The improvements in survival are linked to a deeper understanding of the molecular mechanisms of the disease. Thalidomide, although highly active in MM, is associated with considerable toxicity, particularly in older patients. Immunomodulatory drugs (IMiDs) are structural and functional analogues of thalidomide that represent a promising new class of immunomodulators for treatment of a variety of inflammatory, autoimmune, and neoplastic diseases...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183256/current-and-emerging-treatments-for-metastatic-renal-cell-carcinoma
#4
Carla Cavaliere, Carmine D Aniello, Chiara Della Pepa, Salvatore Pisconti, Massimiliano Berretta, Gaetano Facchini
In the last decades the treatment of mRCC, metastatic Renal Cell Carcinoma, has become more and more complex due to the approval of a great number of effective systemic treatments that have significantly improved the prognosis of patients suffering from such disease. An increasing knowledge of the genetic aberrations and the molecular pathways alterations that underlie RCC, has promoted the development of several novel agents, known as target therapies (TTs). Even though TTs are not curative and all patients eventually progressed, an adequate sequencing of these drugs can provide a significant benefit in terms of PFS, Progression Free Survival, and hopefully OS, Overall Survival...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183255/melanoma-adjuvant-treatment-current-insight-and-clinical-features
#5
Carmine D Aniello, Francesco Perri, Giuseppina Della Vittoria Scarpati, Chiara Della Pepa, Salvatore Pisconti, Vincenzo Montesarchio, Nicolas Wernert, Mayra Rachele Zarone, Michele Caraglia, Gaetano Facchini, Massimiliano Berretta, Carla Cavaliere
Melanoma represents 2-3% of all cancers, 95% of them arise from skin, while only 5% are non-cutaneous melanoma. Despite an optimal surgery management, the risk of a local and systemic relapse remains high, particularly in high-risk patients (node-positive or node-negative T3b, T4 a/b). We conducted a systematic review of the main published and ongoing phase I/II/III trials between 2000 and June 2015 on the adjuvant treatment of cutaneous melanoma. The IFN remains the only option currently available for this aim...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183254/metastatic-colorectal-cancer-role-of-target-therapies-and-future-perspectives
#6
Anna Nappi, Massimiliano Berretta, Carmela Romano, Salvatore Tafuto, Antonino Cassata, Rossana Casaretti, Lucrezia Silvestro, Chiara De Divitiis, Lara Alessandrini, Francesco Fiorica, Alessandro Ottaiano, Guglielmo Nasti
Today, we are experiencing a real cultural revolution in the therapeutic approach to cancer of the colon - rectum, that, by orphan disease, it is now becoming an important paradigm of scientific innovations and concepts. Survival of patients with metastatic colorectal cancer (m-CRC) has been significantly improved with the introduction of the monoclonal antibodies that have as target the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). Novel agents such as aflibercept and regorafenib have recently been approved...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183253/optimal-management-of-prostate-cancer-based-on-its-natural-clinical-history
#7
Gaetano Facchini, Francesco Perri, Gabriella Misso, Carmine D Aniello, Giuseppina Della Vittoria Scarpati, Sabrina Rossetti, Chiara Della Pepa, Salvatore Pisconti, Gerhard Unteregger, Alessia Cossu, Michele Caraglia, Massimiliano Berretta, Carla Cavaliere
Prostate cancer is the most common malignancy in males and, despite a marked improvement in diagnostic techniques, a not small percentage of prostate tumours is still diagnosed in advanced stage. It is now clear that prostate cancer passes through distinct phases during its natural history, starting from an initial phase, in which the disease has a locoregional extent, until a very late phase when it becomes refractory to hormone therapy. It is important to distinguish between local disease, in which tumor may be considered localized in the gland and a systemic disease characterized by high tumor burden and/or dissemination of circulating tumour cells...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183252/pharmacological-profile-and-pharmacogenomics-of-anti-cancer-drugs-used-for-targeted-therapy
#8
Raffaele Di Francia, Angela De Monaco, Mariangela Saggese, Giancarla Iaccarino, Stefania Crisci, Ferdinando Frigeri, Rosaria De Filippi, Massimiliano Berretta, Antonio Pinto
Drugs for targeted therapies are primarily Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA molecules and microRNA. The use of these new agents generates a multifaceted step in the pharmacokinetics (PK) of these drugs. Individual PK variability is often large, and unpredictability observed in the response to the pharmacogenetic profile of the patient (e.g. cytochome P450 enzyme), patient characteristics such as adherence to treatment and environmental factors. Objective This review aims to overview the latest anticancer drugs eligible for targeted therapies and the most recent finding in pharmacogenomics related to toxicity/resistance because either individual gene polymorphisms or acquired mutation in a cancer cell...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183251/the-real-impact-of-target-therapy-in-breast-cancer-patients-between-hope-and-reality
#9
Sebastiano Bordonaro, Massimiliano Berretta, Antonino Carmelo Tralongo, Silvia Clementi, Brigida Stanzione, Paolo Tralongo
Over the last 15 years, we have seen a huge expansion of the development of drugs directed against biomolecular targets within breast cancer cells. The over-expression of certain receptors (ER, PgR, HER-2, VEGF-R), as well as alteration of several intracellular signal transduction pathways (the PI3K-AKT-mTOR pathway, MEK-MAPK pathway, loss of PTEN, etc ...) have a great impact on the likelihood of recurrence and progression of the disease, influencing the natural history of breast cancer. The recent biomolecular classification of breast cancer (Luminal A / B, HER2-driven, Basal Like) allowed finally to identify specific treatments against molecular target to associate or not to traditional chemotherapy, and to use in relation to the prognosis of the disease...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183250/the-role-of-target-therapy-in-the-treatment-of-gastrointestinal-non-colorectal-cancers-clinical-impact-and-cost-consideration
#10
Massimiliano Berretta, Raffaele Di Francia, Chiara De Diviitis, Guglielmo Nasti, Vincenzo Canzonieri, Michele Caraglia, Gaetano Facchini, Umberto Tirelli
Gastrointestinal (GI) tumors are a leading cause of cancer-related deaths in the world. In fact, gastric cancer (GC) is the third cause of cancer deaths, whereas aesophageal neoplasm is the eighth most common cancer worldwide and its incidence, especially adenocarcinoma type, is continuously increasing. Also Hepatocellular carcinoma, Cholangiocarcinoma and pancreatic cancer represent a very interesting model to multidisciplinary approach and recently new drugs are used in their treatment. Currently, new clinical trials are designed including classic chemotherapy in association with either small molecule inhibitors (i...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176648/oncolytic-viruses-the-best-is-yet-to-come
#11
Chantal G Lemay, Brian A Keller, Robert E Edge, Masato Abei, John C Bell
Oncolytic viruses are a promising anti-cancer platform, achieving significant pre-clinical and clinical milestones in recent years. A full arsenal of selective, safe, and effective viruses has been developed with some emerging pre-clinical research focusing on optimizing these therapies in the face of remaining challenges, both in the bloodstream and in the tumour microenvironment. Herein we discuss the recent progress in pre-clinical virotherapy research to address these challenges, with special focus on innovative strategies that seek to complement the current strengths of virotherapy, ensuring an optimal multi-faceted attack on cancer...
February 6, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176647/clinical-effectiveness-and-cost-effectiveness-of-target-therapies-for-adult-patients-with-locally-advanced-or-metastatic-non-small-cell-lung-cancer-a-systematic-review
#12
Alessandra Bearz, Massimiliano Berretta, Umberto Tirelli
Treatment for advanced non-small cell lung cancer has changed in the last two decades, with many new drugs, mostly target agents, included in the algorithm, improvement of progression free survival and overall survival, but also higher costs for health systems or health insurances. Herein, we analyze the clinical effectiveness of target therapies for non-small cell lung cancer, according to their clinically meaningful outcome criteria and their cost impact.
February 6, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176653/multimodal-hdac-inhibitors-with-improved-anticancer-activity
#13
Rainer Schobert, Bernhard Biersack
Histone deacetylases (HDACs) play a significant role in the proliferation and dissemination of cancer and represent promising epigenetic drug targets. The HDAC inhibitor vorinostat featuring a zinc-binding hydroxamate fragment was already clinically approved. However, HDAC inhibitors containing hydroxamic acids are often hampered by acquired or intrinsic drug resistance and may lead to enhanced tumor aggressiveness. In order to overcome these drawbacks of hydroxamate HDAC inhibitors a series of multimodal derivatives of this compound class, including such with different zinc-binding groups, was recently developed and showed promising anticancer activity...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176652/mechanisms-for-inhibition-of-colon-cancer-cells-by-sulforaphane-through-epigenetic-modulation-of-microrna-21-and-human-telomerase-reverse-transcriptase-htert-down-regulation
#14
Samantha L Martin, Rishabh Kala, Trygve O Tollefsbol
Epigenetic modulations such as histone modifications are becoming increasingly valued for their ability to modify genes without altering the DNA sequence. Many bioactive compounds have been shown to alter genetic and epigenetic profiles in various forms of 6 cancers. Of the many dietary phytochemicals, sulforaphane (SFN), found in cruciferous vegetables such as kale, cabbage and broccoli sprouts, has been present as one of the most potent (histone deacetylase) HDAC inhibitors to date. Recently, it has been 9 identified that HDAC inhibitors may play a vital role in regulating microRNAs (miRNAs) in many human cancers...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176651/lung-cancer-stem-cells-an-epigenetic-perspective
#15
Samriddhi Shukla, Sajid Khan, Sonam Sinha, Syed Musthapa Meeran
Lung cancer remains the major cause of human mortality among all the cancer types despite the colossal amount of efforts to prevent the cancer onset and to provide the appropriate cure. Recent reports have identified that important contributors of lung cancer-related mortality are the drug resistance and aggressive tumor relapse, the characteristics contributed by the presence of lung cancer stem cells (CSCs). The identification of lung CSCs is inherently complex due to the quiescent nature of lung epithelium, which makes the distinction between the normal lung epithelium and lung CSCs difficult...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176650/is-there-a-role-for-epigenetic-enhancement-of-immunomodulatory-approaches-to-cancer-treatment
#16
Kirsty J Flower, Sadaf Ghaem-Maghami, Robert Brown
The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting by the host could itself select for immune-evasive tumour cells during tumour development leading to immunotherapy resistance...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176649/oncolytic-herpes-simplex-virus-vectors-fully-retargeted-to-tumor-associated-antigens
#17
Hiroaki Uchida, Hirofumi Hamada, Kenji Nakano, Heechung Kwon, Hideaki Tahara, Justus B Cohen, Joseph C Glorioso
Oncolytic virotherapy is a novel therapeutic modality for malignant diseases that exploits selective viral replication in cancer cells. Herpes simplex virus (HSV) is a promising agent for oncolytic virotherapy due to its broad cell tropism and the identification of mutations that favor its replication in tumor over normal cells. However, these attenuating mutations also tend to limit the potency of current oncolytic HSV vectors that have entered clinical studies. As an alternative, vector retargeting to novel entry receptors has the potential to achieve tumor specificity at the stage of virus entry, eliminating the need for replication-attenuating mutations...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176656/outlook-on-epigenetic-therapeutic-approaches-for-treatment-of-gastric-cancer
#18
Petra Hudler
The incidence of gastric cancer has been declining globally in the last decades. Despite the improvements in the diagnostic procedures, most cases are still detected at advanced stages due to lack of specific symptoms associated with early phases of tumour development. Consequently, gastric cancer poses a major health burden worldwide due to high mortality rates. Continuing advances in high-throughput technologies are revealing an intricate network of genetic and epigenetic changes associated with carcinogenesis...
February 3, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176655/epigenetics-in-clinical-management-of-children-and-adolescents-with-brain-tumors
#19
Andres Morales La Madrid, Mark W Kieran
Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages -not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the "classic" current therapeutic approaches...
February 3, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176654/transforming-cancer-epigenetics-using-nutritive-approaches-and-non-coding-rnas
#20
Centdrika R Dates, Trygve O Tollefsbol
Cancer is considered one of the leading causes of death in the United States. Although preventive strategies, early detection, and improved treatment options have been developed, novel targets and therapeutics are still needed. Since concluding that cancer is mediated by genetic and epigenetic alterations of the cell, many research groups are now focusing on other means of prevention and therapy via nutrition, epigenetic mechanisms, and non-coding RNAs which have been shown to control gene expression and have many different functions at the cellular level...
February 3, 2017: Current Cancer Drug Targets
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