Search results for "Progression"
showing 10 items of 1251 documents
Refining sorafenib therapy: lessons from clinical practice
2015
ABSTRACT Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symp…
Tumor and its microenvironment: a synergistic interplay.
2013
The mutual and interdependent interaction between tumor and its microenvironment is a crucial topic in cancer research. Recently, it was reported that targeting stromal events could improve efficacies of current therapeutics and prevent metastatic spreading. Tumor microenvironment is a "complex network" of different cell types, soluble factors, signaling molecules and extracellular matrix components, which orchestrate the fate of tumor progression. As by definition, cancer stem cells (CSCs) are proposed to be the unique cell type able to maintain tumor mass and survive outside the primary tumor at metastatic sites. Being exposed to environmental stressors, including reactive oxygen species …
Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary off-target of tyrosine kinase inhibitors.
2011
c-Kit tyrosine kinase receptor and its ligand stem cell factor have multiple functions during development, whereas in adulthood they are mostly needed for stem cell (SC) maintenance and mast cell (MC) biology. c-Kit plays an essential tumor-cell-intrinsic role in many types of cancer, either providing the tumorigenic force when aberrantly activated or conferring stem-like features characterizing the most aggressive variants. A tumor-cell-extrinsic role occurs through c-Kit-dependent accessory cells (such as MCs) that infiltrate tumors and deeply influence their progression. c-Kit-targeted therapy with tyrosine kinase inhibitors (TKIs) may ideally work against both tumor and stromal cells. H…
Statin use improves the efficacy of nivolumab in patients with advanced renal cell carcinoma
2022
Background: Statins are widely used in an ageing population, including subjects with solid malignancies. However, no conclusive evidence is currently available on their potential influence on patients' outcome. We aimed to assess whether statin exposure affects the survival of patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.Patients and methods: Medical records of patients with documented mRCC treated with second- or third-line nivolumab were reviewed at ten institutions from Italy, Spain and the USA. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit. Univariate and multivariate analyses were used to e…
Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma.
1997
Escape from immune surveillance is critical for tumor progression in metastatic melanoma. We assessed the function of melanoma-derived dendritic cells (DCs) in patients presenting simultaneously with responding (rM) or progressing (pM) melanoma metastases. These rare coincidences allowed us to compare syngeneically the function of tumor DCs. CD83+ DCs were purified freshly from large responding (rDCs) or progressing (pDCs) metastases following chemo-immunotherapy. rDCs were 5 times more potent inducers of allogeneic T-cell proliferation than the pDCs that were used as control. Phenotypic analysis showed a marked depression of CD86 expression on pDCs. Culture supernatants from pM showed prod…
Abstract A24: Bone marrow hematopoietic adaptation as a sensor of early, pre-invasive, epithelial malignancy
2018
Abstract Tumor development and progression is in part dependent on the ability of bystander cells, mostly of bone marrow (BM) origin, to establish a pro-tumorigenic microenvironment. We hypothesized that signs of the cross-talk between elements of the tumor microenvironment and the BM can be identified in the very early phases of cancer development, being finalized to the instruction of a tumor-promoting hematopoiesis. By integrating in situ BM histopathological and immunophenotypical analyses with flow cytometry and gene expression profiling of hematopoietic populations in a spontaneous mouse model of breast carcinogenesis (MMTV/NeuT) we investigated the occurrence and quality of modificat…
Abstract 2141: Stromal SPARC deficiency skews prostate cancer toward neuroendocrine differentiation
2018
Abstract Tumor progression is a multifaceted process in which, complex interactions between tumor and different types of stromal cells and extracellular matrix components, actively contribute to its phenotypic heterogeneity. Among extracellular matrix proteins, secreted protein acidic and rich in cysteine (SPARC) has been deeply studied since conflicting reports have described its expression to be either increased or decreased in different cancer settings, also depending on whether it is produced by the neoplasm or by the neighboring stroma. Nevertheless, the different contribution of tumor- or stromal-derived SPARC in prostate tumor microenvironment has not been addressed at least for tumo…
Abstract LB-099: Metabolic vulnerabilities of mesenchymal-like EGFR-mutant NSCLC cells with acquired resistance to tyrosine kinase inhibitors
2018
Abstract Despite the availability of the effective targeted therapies in lung cancer, such as EGFR tyrosine kinase inhibitors (TKIs), drug tolerance and acquired resistance are two common problems that negatively impact lung cancer patient survival. Consequently it is important to understand the molecular basis of the drug tolerance and resistance so that we could formulate effective strategies to ameliorate the efficacy of existing drug and to suppress the emergence of drug resistance. A burgeoning body of literature demonstrated that epigenetic changes by the methylation of DNA and histones are critical in acquired drug resistance, especially in those cancer cells with stem cell-like prop…
Abstract A22: PanDrugsDB: Identifying druggable genetic dependencies for personalized cancer therapy
2015
Abstract The paradigm of personalized medicine is the identification of the appropriate drug for the right patient, using molecular profiles. In Oncology, it is well established that the anticancer drugs are effective in only a small subset of patients. Moreover, many of the new targeted therapies inhibit specific proteins, and they are only effective in tumors that are genetically altered. Consequently, the success of personalized treatment depends on each individual molecular profile, which a priori can be considered as very heterogeneous. Here, we present a new computational approach (PanDrugsDB) based on the analysis and integration of genomic data (mutations, copy number variations or …
Differential expression of tumorspheres in CSC-markers and signaling pathways from non-small cell lung cancer.
2016
e23276Background: Chemoresistance, tumor progression and metastasis have made of lung cancer the first cause of death cancer-related worldwide. Cancer stem cells (CSCs) are small subpopulations of ...