Search results for "muta"

HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer.

2015

Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We fur…

The tumour microenvironment as an integrated framework to understand cancer biology

2019

Cancer cells all share the feature of being immersed in a complex environment with altered cell-cell/cell-extracellular element communication, physicochemical information, and tissue functions. The so-called tumour microenvironment (TME) is becoming recognised as a key factor in the genesis, progression and treatment of cancer lesions. Beyond genetic mutations, the existence of a malignant microenvironment forms the basis for a new perspective in cancer biology where connections at the system level are fundamental. From this standpoint, different aspects of tumour lesions such as morphology, aggressiveness, prognosis and treatment response can be considered under an integrated vision, givin…

Molecular pathway activation – New type of biomarkers for tumor morphology and personalized selection of target drugs

2018

Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in cancer development and progression, being deeply implicated in intracellular signaling pathways. To date, hundreds of different ATDs were approved for clinical use in the different countries. Compared to previous chemotherapy treatments, ATDs often demonstrate reduced side effects and increased efficiency, but also have higher costs. However, the efficiency of ATDs for the advanced stage tumors is still insufficient. Different ATDs have different mechanisms of action and are effective in different cohorts of patients. Personalized approaches are therefore needed to select the best ATD…

Editorial: Cell Stress, Metabolic Reprogramming, and Cancer

2018

Molecular subtyping of colon cancer (CC) based on mutational status of RAS, BRAF, and DNA mismatch repair (MMR) proteins. Prognostic value.

2016

e15094Background: CC is a heterogeneuous disease with clinical, pathological and biological variability. Molecular classification could indentify prognostic subtypes. Methods: 105 patients with sta...

Abstract IA06: Targeting the mutanome for individualized cancer immunotherapy

2016

Abstract Mutations are regarded as ideal targets for cancer immunotherapy. As neo-epitopes with strict lack of expression in any healthy tissue, they are expected to be safe. The systematic use of mutations for vaccine approaches, however, is hampered by the uniqueness of the repertoire of mutations (the mutanome) in every patient's tumor. We have recently proposed a personalized immunotherapy approach targeting the spectrum of individual mutations. Preclinically we could show in three independent murine tumor models that a considerable fraction of non-synonymous cancer mutations is immunogenic and that unexpectedly the immunogenic mutanome is pre-dominantly recognized by CD4+ T cells (the …

Follow up analysis by exosomal miRNAs in EGFR mutated non-small cell lung cancer (NSCLC) patients during osimertinib (AZD9291) treatment: A potential…

2016

e23035Background: NSCLC patients harboring EGFR mutations are able to receive approved tyrosine kinase inhibitors (TKIs) but to better assess the treatment responses new tools are needed. Liquid bi...

Molecular Basis of Mismatch Repair Protein Deficiency in Tumors from Lynch Suspected Cases with Negative Germline Test Results

2020

Some 10&ndash

Exploiting Gangliosides for the Therapy of Ewing’s Sarcoma and H3K27M-Mutant Diffuse Midline Glioma

2021

Simple Summary Osteosarcoma, Ewing’s sarcoma, and H3K27M-mutant diffuse midline glioma are rare but aggressive malignancies occurring mainly in children. Due to their rareness and often fatal course, drug development is challenging. Here, we repurposed the existing drugs dinutuximab and eliglustat and investigated their potential to directly target or indirectly modulate the tumor cell-specific ganglioside GD2. Our data suggest that targeting and/or modulating tumor cell-specific GD2 may offer a new therapeutic strategy for the above mentioned tumor entities. Abstract The ganglioside GD2 is an important target in childhood cancer. Nevertheless, the only therapy targeting GD2 that is approve…

Abstract 2810: Pterostilbene, a natural phytoalexin, weakens the antioxidant defenses of aggressive cancer cells in vivo: a pituitary gland- and Nrf2…

2016

Abstract Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies lack of correlation to the bioavailable concentrations is a critical issue. We studied the underlying mechanisms using different human melanomas (A2058, MeWo and MelJuso) and pancreatic cancers (AsPC-1 and BxPC-3) (with genetic backgrounds correlating with most tumors in patients), growing in nude mice as xenografts, and pterostilbene (Pter, 3’,5’-dimethoxy-4-stilbenol; abundant in e.g. blueberries and a natural dimethoxylated analog of resveratrol). RESULTS: Intravenous administration of Pter decreased human melanoma and pancreatic cancer growth (an effect associated with lower rates of tumor c…