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Immunotherapy, targeted therapy

S Sengupta, G Mao, Z S Gokaslan, P Sampath
Glioblastoma (GBM) is by far the most common and the most aggressive of all the primary brain malignancies. No curative therapy exists, and median life expectancy hovers at around 1 year after diagnosis, with a minute fraction surviving beyond 5 years. The difficulty in treating GBM lies in the cancer's protected niche within the blood-brain barrier and the heterogeneity of the cancer cells, which possess varying degrees of susceptibility to various common modalities of treatment. Over time, it is the tumor heterogeneity of GBM and the ability of the cancer stem cells to evolve in response treatment that renders the cancer refractory to conventional treatment...
October 21, 2016: Cancer Gene Therapy
Marta Polkowska, Edyta Czepielewska, Małgorzata Kozłowska-Wojciechowska
Advanced melanoma is related to a very grim prognosis and fast progression. Until recently, there has been no indicated treatment that would affect the disease's outcome. However, the progress in immunotherapy and molecular therapy has significantly changed the unfavourable prognosis of melanoma progression and its short survival rate. Both approaches have improved patients' outcomes and provided renewed hope for successful treatment. Moreover, in order to further enhance patients' outcomes and to avoid mechanisms of tumour resistance, investigators attempted a combined approach...
December 2016: Current Treatment Options in Oncology
Shouzheng Wang, Junling Li
In recent years, squamous non-small cell lung cancer (NSCLC) didn't progress much in chemotherapy or target therapy. However, immunotherapy has made breakthroughs in treating squamous NSCLC. Immunotherapy includes two main broad classes of immune checkpoint inhibitors and therapeutic vaccines. Immune checkpoint inhibitors, including anti cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and anti programmed death receptor 1 (PD-1) antibodies, have been tested in the phase II/III clinical trials and have demonstrated promising outcomes...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
C Grassberger, H Paganetti
The variety of treatment options for cancer patients has increased significantly in recent years. Not only do we combine radiation with surgery and chemotherapy, new therapeutic approaches such as immunotherapy and targeted therapies are starting to play a bigger role. Physics has made significant contributions to radiation therapy treatment planning and delivery. In particular, treatment plan optimization using inverse planning techniques has improved dose conformity considerably. Furthermore, medical physics is often the driving force behind tumor control and normal tissue complication modeling...
October 19, 2016: Physics in Medicine and Biology
Peter L Stern, Richard Harrop
The natural history of a patient's cancer is often characterised by genetic diversity and sequential sweeps of clonal dominance. It is therefore not surprising that identifying the most appropriate tumour-associated antigen for targeted intervention is challenging. The 5T4 oncofoetal antigen was identified by searching for surface molecules shared between human trophoblast and cancer cells with the rationale that they may function to allow survival of the foetus as a semi-allograft in the mother or a tumour in its host...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
David J Pinato, Robert J Shiner, Solomon D T White, James R M Black, Pritesh Trivedi, Justin Stebbing, Rohini Sharma, Francesco A Mauri
Purpose: There is inconclusive evidence to suggest the expression of programmed cell death (PD) ligand 1 (PD-L1) is a putative predictor of response to PD-1/PD-L1-targeted therapies in lung cancer. We evaluated the heterogeneity in the expression of PD-1 ligands in isogeneic primary and metastatic LC specimens. Experimental Design: From 12,580 post mortem cases, we identified 214 patients with untreated metastatic LC, of which 98 had adequately preserved tissues to construct a syngeneic primary LC/metastasis tissue microarray...
2016: Oncoimmunology
Leonid Dubrovsky, Elliott Joseph Brea, Dmitry Pankov, Emily Casey, Tao Dao, Cheng Liu, David A Scheinberg
Specific immunotherapy for acute leukemia remains a great unmet need. Native unmodified monoclonal antibody therapies, while promising, are inadequately effective for these malignancies, and multiple mechanisms for failure have been described. Antibody-dependent cellular cytotoxicity or phagocytosis is the primary modality of mAb-mediated cell killing in vivo, but ultimately leads to relapse of the leukemias, in model systems and in humans. By use of a T-cell receptor mimic mAb ESKM, derived against a WT1 peptide expressed in complex with HLA-A*02:01, whose only mechanism of therapeutic action is ADCC, we evaluated the mechanisms of leukemic relapse from its potent therapeutic action in mouse xenograft models of human leukemia...
2016: Oncoimmunology
N R Datta, S Krishnan, D E Speiser, E Neufeld, N Kuster, S Bodis, H Hofmann
Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology...
October 3, 2016: Cancer Treatment Reviews
Yini Wang, Zhao Wang
PURPOSE OF REVIEW: Hemophagocytic lymphohistiocytosis (HLH) is a condition of uncontrolled immune activation with a high mortality rate. The recommended therapeutic guideline for HLH was published by the Histiocyte Society in 1994 and revised in 2004, which greatly improved the survival in patients with HLH. However, HLH is still a refractory disease for which the search for novel treatments continues. This article overviewed recent advances in treatment of HLH. RECENT FINDINGS: Current practices in treatment extend from chemo-immunotherapy to some new cytokine-targeting biologicals, which are more effective to eliminate pathologically activated T cells and resist exaggerated cytokine storm...
October 15, 2016: Current Opinion in Hematology
Chad R Ritch, Michael S Cookson
Docetaxel based chemotherapy showed survival benefit and emerged as the mainstay of treatment for castration resistant prostate cancer (CRPC) in 2004. However, therapeutic options have expanded rapidly since 2011. The spectrum of new agents is broad and includes drugs that target the androgen axis (enzalutamide, abiraterone), immunotherapy (sipuleucel-T), bone seeking radionuclides (radium-223), and second line chemotherapy (cabazitaxel). In addition, new agents have been developed to reduce skeletal related events (denosumab)...
October 17, 2016: BMJ: British Medical Journal
Yi Zheng, Yicheng Yang, Shu Wu, Yongqiang Zhu, Xiaolong Tang, Xiaopeng Liu
As the second most common gynecologic malignant tumors with a high mortality rate, cervical cancer jeopardizes women's life worldwide. The low cure rate in cervical cancer patients is mainly attributed to the lack of effective therapies. One feasible novel strategy is to develop immune-based approaches such as adoptive cell immunotherapy of DCCIKs which represents a promising nontoxic antineoplastic immunotherapy preferred in clinic practice. However, the therapeutic effect is not as efficient as anticipated...
October 18, 2016: Bioengineered
Alireza Bolourian, Zahra Mojtahedi
Mammalian target of rapamycin (mTOR) inhibitors are strong anti-tumor drugs; however, they have adverse immunosuppressive side effects in some cancer patients. Animal studies have provided evidence that mTOR inhibitors improved tumor-specific T-cells adoptive transfer in which the quality of CD8+ T-cells is a major factor for predicting success. Interestingly, mTOR inhibitors are capable of stimulating cytotoxic CD8+ T-cell if their dose/duration is adjusted. Rapamycin-induced CD8+ T-cells have also been associated with tumor immunity in animal models...
July 2016: Archives of Medical Research
Jimmy Hwang
Esophagogastric cancers (EGCa) are a leading cause of cancer related mortality worldwide. It has been recognized that they represent heterogenous diseases based on histology and anatomy. However, it is also increasingly evident that these are diverse malignancies based on genetic alterations, and this is increasingly making these diseases amenable to targeted therapies. While epidermal growth factor receptor (EGFR) and mTOR inhibitors have failed to prove effective in the treatment of advanced EGCa, vascular endothelial growth factor (VEGF) inihibitor have now been demonstrated to improve survival, at least in the 2nd line setting of adenocarcinomas...
October 2016: Journal of Gastrointestinal Oncology
Manojkumar Bupathi, Christina Wu
Colorectal cancer (CRC) is a heterogeneous disease for which the treatment backbone has primarily been cytotoxic chemotherapy. With better understanding of the involved molecular mechanisms, it is now known that there are a number of epigenetic and genetic events, which are involved in CRC pathogenesis. Specific biomarkers have been identified which can be used to determine the clinical outcome of patients beyond tumor staging and predict for treatment efficacy. Molecular testing is now routinely performed to select for patients that will benefit the most from targeted agents and immunotherapy...
October 2016: Journal of Gastrointestinal Oncology
Noelle V Frey, David L Porter
Chimeric antigen receptors (CARs) are engineered molecules that can be introduced into T cells to enable them to target specific tumor antigens. CAR T cells targeting CD19 have shown promise in patients with relapsed and refractory B-cell neoplasms, including those with acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphomas. Notably, durable responses have been observed in patients who had not undergone consolidative stem cell transplant, a finding that correlates with reports of T-cell persistence and B-cell aplasia in studies of anti-CD19 treatment in vivo...
October 15, 2016: Oncology (Williston Park, NY)
C Gzell, M Back, H Wheeler, D Bailey, M Foote
The aim of this review is to explore the changing utility of radiotherapy in the treatment of patients with glioblastoma over the past 60 years. Together with surgery, radiotherapy has always been the cornerstone of treatment of glioblastoma, but techniques have significantly advanced over this time. The exploration of early two-dimensional techniques, investigation of dose escalation, concomitant chemotherapy and modern techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, and volumetric-modulated arc therapy will be covered...
October 13, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
Rafael Morales-Barrera, Cristina Suárez, Ana Martínez de Castro, Fabricio Racca, Claudia Valverde, Xavier Maldonado, Juan Maria Bastaros, Juan Morote, Joan Carles
Bladder cancer is one of the leading causes of death in Europe and the United States. About 25% of patients with bladder cancer have advanced disease (muscle-invasive or metastatic disease) at presentation and are candidates for systemic chemotherapy. In the setting of metastatic disease, use of cisplatin-based regimens improves survival. However, despite initial high response rates, the responses are typically not durable leading to recurrence and death in the vast majority of these patients with median overall survival of 15months and a 5-year survival rate of ⩽10%...
October 1, 2016: Cancer Treatment Reviews
Dan Ishihara, Laurentiu Pop, Tsuguhide Takeshima, Puneeth Iyengar, Raquibul Hannan
Cancer immunotherapy exploits the immune system's ability to differentiate between tumor target cells and host cells. Except for limited success against a few tumor types, most immunotherapies have not achieved the desired clinical efficacy until recently. The field of cancer immunotherapy has flourished with a variety of new agents for clinical use, and remarkable progress has been made in the design of effective immunotherapeutic regimens. Furthermore, the therapeutic outcome of these novel agents is enhanced when combined with conventional cancer treatment modalities including radiotherapy (RT)...
October 14, 2016: Cancer Immunology, Immunotherapy: CII
Januario E Castro, Thomas J Kipps
Treatment of patients with chronic lymphocytic leukemia and other B cell malignancies is evolving very rapidly. We have observed the quick transition during the last couple of years, from chemo-immunotherapy based treatments to oral targeted therapies based on B cell receptor signaling and Bcl-2 inhibitors, as well as the increasing use of second generation glyco-engineered antibodies. The next wave of revolution in the treatment for this conditions is approaching and it will be based on strategies that harness the power of the immune system to fight cancer...
March 2016: Best Practice & Research. Clinical Haematology
Hongjiu Yu, Yonggui Ge, Lianying Guo, Lin Huang
Ewing's sarcoma (ES) is a highly aggressive and metastatic tumor in children and young adults caused by a chromosomal fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene and the transcription factor FLI1 gene. ES is managed with standard treatments, including chemotherapy, surgery and radiation. Although the 5-year survival rate for primary ES has improved, the survival rate for ES patients with metastases or recurrence remains low. Several novel molecular targets in ES have recently been identified and investigated in preclinical and clinical settings, and targeting the function of receptor tyrosine kinases (RTKs), the fusion protein EWS-FLI1 and mTOR has shown promise...
October 11, 2016: Oncotarget
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