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Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.

Neuroendocrine neoplasms (NENs), which are characterized by neuroendocrine differentiation, can arise in various organs. NENs have been divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) based on morphological differentiation, each of which has a distinct etiology, molecular profile, and clinicopathological features. While the majority of NECs originate in the pulmonary organs, extrapulmonary NECs occur most predominantly in the gastro-entero-pancreatic (GEP) system. Although platinum-based chemotherapy is the main therapeut

Marizomib in the therapy of brain tumors-how far did we go and where do we stand?

Out of several types of tumors of the central nervous system (CNS), glioblastoma (GBM) represents one of the most frequent and malignant forms of brain neoplasms. To date, GBM holds very limited therapeutic options leaving patients with poor prognosis of survival. As such, novel treatment approaches are constantly quested. One of these strategies is based on the utilization of proteasome inhibitors (PIs). However, although several PIs have been approved as therapy for patients with hematological malignancies, these treatment benefits cannot not be easily extrapolated to brain tumors. This is m

Potential role of immunotherapy and targeted therapy in the treatment of cancer: A contemporary nursing practice.

Immunotherapy and targeted therapy have emerged as promising therapeutic options for cancer patients. Immunotherapies induce a host immune response that mediates long-lived tumor destruction, while targeted therapies suppress molecular mechanisms that are important for tumor maintenance and growth. In addition, cytotoxic agents and targeted therapies regulate immune responses, which increases the chances that these therapeutic approaches may be efficiently combined with immunotherapy to ameliorate clinical outcomes. Various studies have suggested that combinations of therapies that target diff

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… , 81 ] Romidepsin | Cutaneous T-cell lymphoma (CTCL) | Anemia, anorexia, vomiting, fatigue, nausea, thrombocytopenia, neutropenia, infections, lymphopenia | [ 82 , 83 ] Panobinostat | Multiple myeloma | Pyrexia, vomiting, fatigue, nausea, decreased appetite, peripheral edema, diarrhea | [ 84 , 85 ] Vorinostat … Update on the treatment of cutaneous T-cell lymphoma (CTCL): focus on vorinostat. Biologics. 2007;1:377. 87. Stein E.M., DiNardo C.D., Pollyea D.A., Fathi A.T., Roboz G.J., Altman J.K., Stone R.M., Deangelo D.J., Levine R.L., Flinn I.W., et al. …

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma.

Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumo

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… Several compounds that show anticancer efficacy on CCA cells such as norcantharidin [ 145 ], compound C [ 146 ], vorinostat [ 147 ] or cisplatin [ 106 , 141 ] induce the activation of protective autophagy in CCA cells, and pharmacological inhibition of autophagic process enhances these drugs anti-cancer …

Interplay of non-coding RNAs and approved antimetabolites such as gemcitabine and pemetrexed in mesothelioma.

Gemcitabine and pemetrexed are clinically approved antimetabolites for the therapy of mesothelioma diseases. These drugs are often applied in combination with platinum complexes and other drugs. The activity of antimetabolites depended on the expression levels of certain non-coding RNAs, in particular, of small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The development of tumor resistance towards antimetabolites was regulated by non-coding RNAs. An overview of the interplay between gemcitabine/pemetrexed antimetabolites and non-coding RNAs in mesothelioma is provided. Further to th

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… The synthetic HDAC inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat), which was approved for the treatment of T cell lymphoma, induced the expression of let-7d, miR-15a, miR-16, and miR-34b while the expression of the lncRNA HOTAIR was suppressed by SAHA [ [208] , [209] , [210] , [211] ]. …

Epigenetic reprogramming in multiple myeloma-Challenges and opportunities.

In cancer, mutational processes act in concert with epigenetic reprogramming to endow malignant cells with hallmark properties that underpin tumorigenesis. Compared with the relatively rigid and slow processes of genetic evolution, the plastic nature of chromatin enables cells to adapt to a changing environment more rapidly. Multiple myeloma is characterised by high levels of inter- and intra-patient heterogeneity at both the genetic and epigenetic levels. Understanding the many layers of genetic and non-genetic evolution and their interplay is crucial to improve patient outcomes. In this shor

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… Phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced multiple myeloma. Leuk Lymphoma. 2008;49(3):502‐507. 87. Wolf JL, Siegel D, Goldschmidt H, et al. …

mTOR pathway as a potential therapeutic target for cancer stem cells in canine mammary carcinoma.

Mammary adenocarcinoma, the most common cancer in female dogs, often exhibits the lymph node and lung metastases and has a higher mortality rate. However, mammary adenocarcinoma has no established treatment, except early surgical excision. Canine mammary carcinoma has many common features with human mammary carcinoma, including clinical characteristics, heterogeneity, and genetic aberrations, making it an excellent spontaneous tumor model for human breast cancer. Diverse cancers comprised heterogeneous cell populations originating from cancer stem cells (CSCs) with self-renewal ability. Theref

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… 65.01 mTOR | temsirolimus | 27.64 | 28.30 | 74.66 | 29.27 EGFR/Her2 | lapatinib | 13.43 | 12.21 | 63.35 | 27.28 Bcr-Abl/Kit | imatinib mesylate | 136.30 | 139.07 | 68.33 | 105.99 Multi-kinases | sunitinib malate | 20.27 | 16.76 | 139.37 | 108.65 EGFR | gefitinib | 12.47 | 10.77 | 54.75 | 20.55 HDAC | vorinostat …

Development of an MCL-1-related prognostic signature and inhibitors screening for glioblastoma.

Introduction: The effect of the conventional treatment methods of glioblastoma (GBM) is poor and the prognosis of patients is poor. The expression of MCL-1 in GBM is significantly increased, which shows a high application value in targeted therapy. In this study, we predicted the prognosis of glioblastoma patients, and therefore constructed MCL-1 related prognostic signature (MPS) and the development of MCL-1 small molecule inhibitors. Methods: In this study, RNA-seq and clinical data of 168 GBM samples were obtained from the TCGA website, and immunological analysis, differential gene expressi

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… Bortezomib-induced sensitization of malignant human glioma cells to vorinostat-induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl-1 cleavage, and DNA damage . Mol. …

Carfilzomib enhances cisplatin-induced apoptosis in SK-N-BE(2)-M17 human neuroblastoma cells.

Neuroblastoma is a solid malignant tumor of the sympathetic nervous system, which accounts for 8-10% of childhood cancers. Considering the overall high risk and poor prognosis associated with neuroblastoma, effective therapeutics should be developed to improve patient survival and quality of life. A recent study showed that a proteasome inhibitor, carfilzomib (CFZ), reduced cell viability of SK-N-BE(2)-M17 neuroblastoma cells. Therefore, we investigated the molecular mechanisms by which CFZ lower the cell viability of neuroblastoma cells. CFZ reduced cell viability via cell cycle arrest at G2/

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… Proteasome inhibitor carfilzomib interacts synergistically with histone deacetylase inhibitor vorinostat in Jurkat T-leukemia cells. Acta biochimica et biophysica Sinica. 2014;46:484–491. doi: 10.1093/abbs/gmu030. 44. Zhou Y, Wang K, Zhen S, Wang R, Luo W. …

Paediatric Gliomas: BRAF and Histone H3 as Biomarkers, Therapy and Perspective of Liquid Biopsies.

Paediatric gliomas categorised as low- or high-grade vary markedly from their adult counterparts, and denoted as the second most prevalent childhood cancers after leukaemia. As compared to adult gliomas, the studies of diagnostic and prognostic biomarkers, as well as the development of therapy in paediatric gliomas, are still in their infancy. A body of evidence demonstrates that B-Raf Proto-Oncogene or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) and histone H3 mutations are valuable biomarkers for paediatric low-grade gliomas (pLGGs) and high-grade gliomas (pHGGs). Various diagnostic

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… It has portrayed superior inhibitory activity in vivo to FDA-approved HDAC inhibitors such as vorinostat and romidepsin [ 89 ]. In 2014, Panobinostat was approved by the FDA for the treatment of multiple myeloma [ 20 ]. …

Emerging treatment options for the management of Hodgkin's lymphoma: clinical utility of nivolumab.

Classical Hodgkin's lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell. Enhancing antitumor immune response by targeting PD-1 with the monoclonal antibody

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… Palliative single-agent chemotherapy options include gemcitabine, vinorelbine, vinblastine, bendamustine, liposomal doxorubicin, or biological agents such as lenalidomide, the histone deacetylase inhibitors vorinostat and panobinostat, or the mammalian target of rapamycin inhibitor everolimus. 36 – 46 …

NETs: organ-related epigenetic derangements and potential clinical applications.

High-throughput next-generation sequencing methods have recently provided a detailed picture of the genetic landscape of neuroendocrine tumors (NETs), revealing recurrent mutations of chromatin-remodeling genes and little-to-no pathogenetic role for oncogenes commonly mutated in cancer. Concurrently, multiple epigenetic modifications have been described across the whole spectrum of NETs, and their putative function as tumorigenic drivers has been envisaged. As result, it is still unclear whether or not NETs are epigenetically-driven, rather than genetically-induced malignancies. Although the N

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… First FDA approval Azacitidine | Inhibition of DNA methyltransferases | Myelodysplastic syndromes (FDA, EMA) Acute myeloid leukemia (EMA) Chronic myelomonocytic leukemia (EMA) | 2004 Decitabine | Inhibition of DNA methyltransferases | Myelodysplastic syndromes (FDA) Acute myeloid leukemia (EMA) | 2006 Vorinostat …

Assessment and monitoring of patients receiving chemotherapy for multiple myeloma: strategies to improve outcomes.

Improved understanding as to the biology of multiple myeloma (MM) and the bone marrow microenvironment has led to the development of new drugs to treat MM. This explosion of new and highly effective drugs has led to dramatic advances in the management of MM and underscores the need for supportive care. Impressive and deep response rates to chemotherapy, monoclonal antibodies, and small molecule drugs provide hope of a cure or prolonged remission for the majority of individuals. For most patients, long-term, continuous therapy is often required to suppress the malignant plasma cell clone, thus

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… to report prolonged headaches Hypotension | Dizziness, fatigue | Bortezomib (more common with IV than SC) | •Educate patient on adequate hydration, careful position changes, and to report worsening of the symptom Prolonged QT-c interval | Palpitations; or may be asymptomatic | HDAC-I panobinostat, vorinostat …

FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies.

Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83-9.71) and 2.55- (95%CI 1.52-4.3) in the presence of FN14 and GRP94, respectively.

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… .) = 0.195, vorinostat o.s . = 0.095 and bevacizumab o.s . = 0.078. …

Targeted therapy in the treatment of malignant gliomas.

Malignant gliomas are invasive tumors with the potential to progress through current available therapies. These tumors are characterized by a number of abnormalities in molecular signaling that play roles in tumorigenesis, spread, and survival. These pathways are being actively investigated in both the pre-clinical and clinical settings as potential targets in the treatment of malignant gliomas. We will review many of the therapies that target the cancer cell, including the epidermal growth factor receptor, mammalian target of rapamycin, histone deacetylase, and farnesyl transferase. In additi

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… Thus, the potential exists for HDACIs to influence the cancer cell at many levels. 53 SAHA (suberoylanilide hydroxamic acid, vorinostat, Zolinza ® ; Merck), FDA-approved for cutaneous T-cell lymphoma, is being evaluated in clinical trials of multiple cancers, including malignant gliomas. …

Clinical and Therapeutic Implications of Epstein-Barr Virus in HIV-Related Lymphomas.

The incidence of lymphomas is increased in people living with HIV (PLWH). Aggressive B-cell non-Hodgkin lymphomas (NHLs) are the most common and are considered an AIDS-defining cancer (ADC). Although Hodgkin lymphoma (HL) is not considered an ADC, its incidence is also increased in PLWH. Among all HIV-related lymphomas (HRL), the prevalence of Epstein-Barr virus (EBV) is high. It has been shown that EBV is involved in different lymphomagenic mechanisms mediated by some of its proteins, contributing to the development of different lymphoma subtypes. Additionally, cooperation between both HIV an

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… Some HDAC inhibitors such as vorinostat/suberoylanilide hydroxamic acid (SAHA) have been tested in HL and NHL [ 248 , 249 ]. …

Drug prioritization identifies panobinostat as a tailored treatment element for patients with metastatic hepatoblastoma.

BACKGROUND: Patients with metastatic hepatoblastoma are treated with severely toxic first-line chemotherapies in combination with surgery. Yet, inadequate response of lung metastases to neo-adjuvant chemotherapy still compromises patient outcomes making new treatment strategies, tailored to more efficient lung clearance, mandatory. METHODS: We harnessed a comprehensive patient-derived xenograft platform and a variety of in vitro and in vivo assays to establish the preclinical and biological rationale for a new drug for patients with metastatic hepatoblastoma. RESULTS: The testing of a librar

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… testing platform had only a minimal or moderate effect, we identified the group of microtubule-targeting agents (paclitaxel, vinorelbine, vinblastine, docetaxel, and mebendazole) as well as histone deacetylase (HDAC) inhibitors (panobinostat, rhomidepsin, quisinostat, fimepinostat, belinostat, and vorinostat …

An Analysis Regarding the Association Between Proteasome (PSM) and Hepatocellular Carcinoma (HCC).

BackgroundThe Proteasome (PSM) is a large multi-catalytic protease complex consisting of a 20S core particle and a 19S regulatory particle whose main function is to accept and degrade ubiquitinated substrates, are now considered as one of the potential regulators of tumor proliferation, and stemness maintenance. However, to date, studies on the relationship between PSM and hepatocellular carcinoma (HCC) are limited.MethodsThis study used a bioinformatics approach combining validation experiments to investigate the biological mechanisms that may be related with PSM. A series of experiments in v

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… A genome scale RNAi screen identifies GLI1 as a novel gene regulating vorinostat sensitivity. Cell Death Differ . 2016;23(7):1209–1218. doi: 10.1038/cdd.2015.175 30. Meng Y, Zhao Q, An L, et al. …

Fasting-Mimicking Diet Inhibits Autophagy and Synergizes with Chemotherapy to Promote T-Cell-Dependent Leukemia-Free Survival.

Fasting mimicking diets (FMDs) are effective in the treatment of many solid tumors in mouse models, but their effect on hematologic malignancies is poorly understood, particularly in combination with standard therapies. Here we show that cycles of a 3-day FMD given to high-fat-diet-fed mice once a week increased the efficacy of vincristine to improve survival from BCR-ABL B acute lymphoblastic leukemia (ALL). In mice fed a standard diet, FMD cycles in combination with vincristine promoted cancer-free survival. RNA seq and protein assays revealed a vincristine-dependent decrease in the expressi

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… Targeting the autophagy in bone marrow stromal cells overcomes resistance to vorinostat in chronic lymphocytic leukemia. OncoTargets Ther. 2018;11:5151–5170. doi: 10.2147/OTT.S170392. 35. Galluzzi L., Bravo-San Pedro J.M., Demaria S., Formenti S.C., Kroemer G. …

Are We Ready For "Triplet" Therapy in Higher-Risk MDS?

Higher-risk Myelodysplastic Syndromes/Neoplasms (MDS) represent an ongoing therapeutic challenge, with few effective therapies, many of which may have limited use in this older patient population often with considerations around comorbidities. Outside of transplant, azacitidine and decitabine remain the only disease-modifying therapies, and are palliative in nature. Recent interest has grown in extending combination chemotherapies used to treat acute myeloid leukemia (AML) to patients with MDS, including novel combination chemotherapy "doublets" and "triplets." In this review, we discuss consi

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… Abdel-Wahab Omar Santini Valeria 20 10 2022 36 12 2939 2946 0887-6924 10.1038/s41375-022-01724-9 10.1038/s41375-022-01724-9 36266326 Randomized Phase II Study of Azacitidine Alone or in Combination With Lenalidomide or With Vorinostat in Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic …