journal
https://read.qxmd.com/read/26384009/combinations-therapies
#21
REVIEW
Niels Reinmuth, Martin Reck
Immunotherapy of cancer encompasses different strategies that elicit or enhance the immune response against tumors. The first results from clinical studies have provided promising data for the treatment of lung cancer patients with immunomodulating monotherapies. To improve the potential benefit of cancer immunotherapy, synergistic combinations of the various immunotherapy approaches or of different elements within each of the immunotherapy approaches are being explored. The rationale typically involves different but complementary mechanisms of action, eventually impinging on more than one immune system mechanism...
2015: Progress in Tumor Research
https://read.qxmd.com/read/26383848/radiotherapy-and-immunotherapy-improving-cancer-treatment-through-synergy
#22
REVIEW
Kobe Reynders, Dirk De Ruysscher
Radiotherapy is an important cornerstone in cancer treatment. Ionizing gamma-irradiation is capable of inducing DNA damage and consequential cell death in a precise and effective manner. In recent years it has become clear, however, that this is not the only relevant mechanism of action. Radiotherapy alters the immune composition of the tumor and influences upregulation of MHC I and cancer-testis antigens, inducing immunogenic cell death and supporting dendritic cell activation. Paradoxically, it also increases the relative ratio of regulatory T cells to CD4+ cells, which hampers an effective immune response...
2015: Progress in Tumor Research
https://read.qxmd.com/read/26383626/current-developments-in-actively-personalized-cancer-vaccination-with-a-focus-on-rna-as-the-drug-format
#23
REVIEW
Mustafa Diken, Sebastian Kreiter, Björn Kloke, Ugur Sahin
Developments in sequencing technologies have not only led to a rapid generation of genomic and transcriptional data from cancer patients, but also revealed the vast diversity of cancer-specific changes in patient tumors. Among these, mutation changes in the protein sequence can result in novel epitopes recognized by the immune system and, therefore, can be employed in the development of personalized vaccines. Thanks to its easy design and scalable GMP production, vaccines based on mRNAs coding for mutated epitopes have emerged as a reliable strategy for the exploitation of the potential of patient-specific genomic data...
2015: Progress in Tumor Research
https://read.qxmd.com/read/26383243/t-cell-engineering
#24
REVIEW
Magdalena Pircher, Thomas Schirrmann, Ulf Petrausch
T cells are a new and promising antigen-specific therapeutic option for the treatment of malignant diseases. To achieve antigen specificity against tumor antigens, T cells can be manipulated by gene transfer to express chimeric antigen receptors (CARs). CAR-expressing T cells are called redirected T cells. CARs are composed of an extracellular antibody-derived antigen recognition domain, a transmembrane domain and a cytoplasmatic signal domain. Therefore, redirected T cells combine the exchangeable specificity of an antibody with the cytotoxic machinery of a T cell...
2015: Progress in Tumor Research
https://read.qxmd.com/read/26383097/promise-of-immunotherapy-in-lung-cancer
#25
REVIEW
Anil Shanker, Mikhail M Dikov, David P Carbone
Metastatic lung cancer is the most common cause of cancer mortality globally in both men and women, with 5-year survival of less than 5%. Standard treatment approaches for metastatic lung cancer are based on chemotherapy, with radiation and surgery used for local control, but these rarely result in relapse-free survivals longer than 2-3 years, although they may provide symptom relief. Thus, additional tools are needed to treat this disease. In this chapter, we discuss the various immune-based cancer treatments for lung cancer patients that are being developed, and the increasing awareness that therapies targeted at overcoming immune evasion mechanisms may be essential to clinical efficacy...
2015: Progress in Tumor Research
https://read.qxmd.com/read/26382943/immune-checkpoint-inhibitors
#26
REVIEW
John B A G Haanen, Caroline Robert
Undoubtedly the discovery of immune checkpoints such as CTLA-4 and PD-1 has been crucial to the development of cancer immunotherapy. Although these molecules were originally discovered as molecules playing a role in T cell activation or apoptosis, subsequent preclinical research showed their important role in the maintenance of peripheral immune tolerance. Mice deficient of the immune checkpoints CTLA-4 or PD-1 develop autoimmune-like diseases that occur early after birth and are lethal in the case of CTLA-4 deficiency, or become apparent much later in life in the case of PD-1 deficiency...
2015: Progress in Tumor Research
https://read.qxmd.com/read/26377084/immunotherapy-of-breast-cancer
#27
REVIEW
Carmen Criscitiello, Giuseppe Curigliano
Cancer immunoediting is the process by which the immune system protects the host from tumor development and guides the somatic evolution of tumors by eliminating highly immunogenic tumor cells. A fundamental dogma of tumor immunology and of cancer immunosurveillance in particular is that cancer cells express antigens that differentiate them from their nontransformed counterparts. Molecular studies clearly show that these antigens were often products of mutated cellular genes, aberrantly expressed normal genes, or genes encoding viral proteins...
2015: Progress in Tumor Research
https://read.qxmd.com/read/26376963/immunotherapy-of-melanoma
#28
REVIEW
Alexandra Snyder, Dmitriy Zamarin, Jedd D Wolchok
The history of immunotherapy is rooted in the treatment of melanoma and therapy with immune checkpoint-blocking agents is now a cornerstone for the treatment of metastatic melanoma. The first effective immunotherapies approved by the US Food and Drug Administration in melanoma included interleukin-2 for metastatic disease and interferon alpha in the adjuvant setting. These were followed by a group of new therapies, including checkpoint-blocking antibodies targeting cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1...
2015: Progress in Tumor Research
https://read.qxmd.com/read/26376844/immunotherapies-in-early-and-advanced-renal-cell-cancer
#29
REVIEW
Benjamin Kasenda, James Larkin, Martin Gore
The development of new immunomodulatory monoclonal antibodies targeting the CTLA-4 or PD-1 axis has led to a revival of research on immunotherapies in solid tumours including renal cell cancer (RCC). The initial results observed with these monoclonal antibodies in the treatment of advanced melanoma have resulted in considerable interest in this treatment strategy in all tumour types. Preliminary data of these new antibodies in advanced RCC are promising and they have good safety profiles. Response rates are low but durable tumour control has been observed in some patients...
2015: Progress in Tumor Research
https://read.qxmd.com/read/26376741/immunotherapy-of-brain-tumors
#30
REVIEW
Valérie Dutoit, Denis Migliorini, Paul R Walker, Pierre-Yves Dietrich
Glioma is one of the most devastating cancers, affecting children and young adults, and associated with a very high morbidity and poor prognosis. The propensity of glioma cells to invade normal brain structures makes current treatments poorly efficient and new therapeutic strategies an urgent need. We now know that many of the rules governing immune responses in other tissues are also valid for the brain, providing solid scientific background for developing new strategies exploiting the immune system to fight brain tumors...
2015: Progress in Tumor Research
https://read.qxmd.com/read/24727990/successes-and-limitations-of-targeted-therapies-in-renal-cell-carcinoma
#31
REVIEW
Marc Pracht, Dominik Berthold
Until recently, the standard treatment for metastatic renal cell carcinoma (RCC) was nonspecific immunotherapy based on interleukin-2 or interferon-α. This was associated with a modest survival benefit and with significant clinical toxicities. The understanding of numerous molecular pathways in RCC, including HIF, VEGF, mTOR, and the consecutive use of targeted therapies since the beginning of 2005 have significantly improved outcomes for patients with metastatic RCC with an overall survival greater than 2 years...
2014: Progress in Tumor Research
https://read.qxmd.com/read/24727989/successes-and-limitations-of-targeted-cancer-therapy-in-ovarian-cancer
#32
REVIEW
Giovanna Damia, Cristiana Sessa
In ovarian cancer, the clinical development of anticancer agents targeting DNA repair has been associated with significant results because of the elucidation of the different types of damages and repair systems, including PARP. The discovery of the BRCA mutation and its role in ovarian cancer and the clinical application of the concept of synthetic lethality have been the rationale for the successful testing of PARP inhibitors in BRCA mutated ovarian cancer patients. The recent knowledge of the molecular features of low grade ovarian cancer and the application of the concept of synthetic lethality also in this well-defined pathological entity have prompted the clinical evaluation of a combination of PI3K/MEK inhibitors, the first results of which have been already reported...
2014: Progress in Tumor Research
https://read.qxmd.com/read/24727988/successes-and-limitations-of-targeted-cancer-therapy-in-melanoma
#33
REVIEW
Emanuela Romano, Olivier Michielin
The treatment of stage IV melanoma has witnessed a very impressive pace of innovation in recent years, to a point where the management of these patients has very little in common to what was standard practice 5 years ago. If the gain in overall survival, the high response rates or the induction of a significant fraction of long survivors are all very exciting news for our patients and their families, the path that led to these discoveries is as important. Rather than empirical, the development of these new strategies has been extremely rational, based on state-of-the-art basic biology and immunology, exemplary translational research and, finally, hypothesis-driven targeted trials that led to rapid approval...
2014: Progress in Tumor Research
https://read.qxmd.com/read/24727987/successes-and-limitations-of-targeted-cancer-therapy-in-lung-cancer
#34
REVIEW
Kenichi Suda, Tetsuya Mitsudomi
Human cancers usually evolve through multistep processes. These processes are driven by the accumulation of abundant genetic and epigenetic abnormalities. However, some lung cancers depend on a single activated oncogene by somatic mutation, termed 'driver oncogenic mutations', for their proliferation and survival. EGFR(epidermal growth factor receptor) mutations and ALK(anaplastic lymphoma kinase) rearrangement are typical examples of such driver oncogenic mutations found in lung adenocarcinomas. EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs significantly improved treatment outcomes compared with conventional cytotoxic chemotherapy in patients with lung cancers harboring EGFR mutations or ALK rearrangement, respectively...
2014: Progress in Tumor Research
https://read.qxmd.com/read/24727986/successes-and-limitations-of-targeted-cancer-therapy-in-gastrointestinal-stromal-tumors
#35
REVIEW
Paolo G Casali
In gastrointestinal stromal tumors (GIST), molecularly targeted therapies, starting with imatinib, are directed against an activating mutation of KIT or PDGFRA, which drives the disease. Their efficacy has brought the median survival from one to at least 5 years in the metastatic setting. Tumor response patterns may include tumor shrinkage or not, but are marked by pathologic and radiological changes in tumor tissue. Tumor sensitivity to imatinib can be precisely predicted by the mutational status. However, the metastatic disease has not been truly converted into a chronic condition since secondary resistance to imatinib remains a major limiting factor occurring after a median of 2 years at least in most patients...
2014: Progress in Tumor Research
https://read.qxmd.com/read/24727985/successes-and-limitations-of-targeted-cancer-therapy-in-colon-cancer
#36
REVIEW
Claus-Henning Köhne
Constant development of chemotherapy and more recently the introduction of VEGF- and epidermal growth factor receptor (EGFR)-directed agents have improved significantly the treatment of patients with colorectal cancer. In the adjuvant setting, especially for UICC stage III colon cancer patients, fluoropyrimidine in combination with oxaliplatin is usually the standard of care. With some surprise, both VEGF inhibitors (for all patients) and EGFR (for patients with KRAS exon 2 mutant tumors) have failed to improve adjuvant chemotherapy...
2014: Progress in Tumor Research
https://read.qxmd.com/read/24727984/successes-and-limitations-of-targeted-cancer-therapy-in-breast-cancer
#37
REVIEW
Giuseppe Curigliano, Carmen Criscitiello
Breast cancer is not a single disease. Specific biological processes and distinct genetic pathways are associated with prognosis and sensitivity to chemotherapy and targeted agents in different subtypes of breast cancers. As a consequence, breast cancer can be classified by molecular events. A primary challenge for future drug development in breast cancer will be to distinguish genes and pathways that 'drive' cancer proliferation (drivers) from genes and pathways that have no role in the development of cancer (passengers)...
2014: Progress in Tumor Research
https://read.qxmd.com/read/24727983/targeting-oncogenic-drivers
#38
REVIEW
Yujie Zhao, Alex A Adjei
Cancer is a genetic disease caused by a series of somatic and/or germline mutations. The roles of oncogenes and tumor suppressors in cancer molecular origin have been well established. Targeting oncogene products has become an attractive therapeutic strategy with great clinical success, whereas tumor suppressors are considered 'undruggable' because current technology is not able to restore tumor suppressor function in metastatic disease. Although systematic approaches to discover genetic alterations have become available to individual patients, differentiating driver from passenger mutations and identifying and validating drug targets remain challenging...
2014: Progress in Tumor Research
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