Therapeutically targeting the SUMOylation, Ubiquitination and Proteasome pathways as a novel anticancer strategy.

Abstract:

:The ubiquitin (Ub)+proteasome proteolytic pathway is responsible for the selective degradation of the majority of nuclear and cytosolic proteins. The proteasome is a high molecular weight multicatalytic protease that serves as the catalytic core of the complex Ub-dependent protein degradation pathway and is an exciting new target for the development of novel anticancer therapies. Inhibition of the proteasome, and consequently Ub-dependent proteolysis, with the small molecule pharmacologic agent bortezomib led to approval by the US Food and Drug Administration (FDA) for the treatment of multiple myeloma (MM) that has subsequently been extended to other hematologic malignancies. Inhibition of the proteasome results in the intracellular accumulation of many ubiquitinated proteins that control essential cellular functions such as cellular growth and apoptosis. The accumulation of high molecular weight Ub~protein conjugates eventually triggers apoptosis, with tumor cells more susceptible to proteasome inhibition than non-malignant cells. The defined mechanism of action for proteasome inhibitors has not been completely characterized, not all patients respond to proteasome inhibitor-based therapy, and inevitably patients develop resistance to proteasome inhibitors. Further investigation of the Ub+proteasome system (UPS) is needed to develop more effective inhibitors, to develop agents that overcome bortezomib resistance and to avoid adverse effects such as neuropathy. Furthermore, there are newly uncovered pathways, e.g., the SUMOylation and NEDDylation pathways, which similarly attach Ub-like proteins (ULPs) to protein substrates. The functional consequence of these modifications is only beginning to emerge, but these pathways have been linked to tumorigenesis and may similarly provide therapeutic targets. The immunoproteasome is a specialized form of the proteasome that produces peptides that are presented at the cell surface as major histocompatibility complex (MHC) class I antigens. Proteasome inhibitors decrease the presentation of antigenic peptides to reduce tumor cell recognition by cytotoxic T cells (CTLs) but unexpectedly increase tumor cell recognition by natural killer (NK) cells. Inhibitors of the UPS are validated, cytotoxic agents that may be further exploited in immunotherapy since they modulate tumor cell recognition by effectors of the immune system. Targeting the UPS, SUMOylation and NEDDylation pathways offers great promise in the treatment of hematologic and solid malignancies.

journal_name

Target Oncol

journal_title

Targeted oncology

authors

Driscoll JJ,Dechowdhury R

doi

10.1007/s11523-010-0165-2

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

281-9

issue

4

eissn

1776-2596

issn

1776-260X

journal_volume

5

pub_type

杂志文章,评审
  • Clinical activity of sunitinib in patients with advanced desmoplastic round cell tumor: a case series.

    abstract::Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy with poor outcome occurring in adolescents and young adults. Therapeutic options for patients with advanced disease are limited. Preclinical studies have shown that VEGFR-2 and VEGFA are overexpressed in DSRCT and that DSRCT xenografts wer...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-012-0251-8

    authors: Italiano A,Kind M,Cioffi A,Maki RG,Bui B

    更新日期:2013-09-01 00:00:00

  • Posterior reversible encephalopathy syndrome induced by anti-VEGF agents.

    abstract::Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity that may occur in patients receiving anti-vascular endothelial growth factor (VEGF) agents such as bevacizumab and tyrosine kinase inhibitors. Little is known about the characteristics of patients at risk for PRES under anti-VEGF agen...

    journal_title:Targeted oncology

    pub_type: 杂志文章,meta分析,评审

    doi:10.1007/s11523-011-0201-x

    authors: Tlemsani C,Mir O,Boudou-Rouquette P,Huillard O,Maley K,Ropert S,Coriat R,Goldwasser F

    更新日期:2011-12-01 00:00:00

  • Targeted therapies in thyroid cancer.

    abstract::Differentiated thyroid carcinoma is the most frequent neoplasm of the endocrine system. Although thyroid cancer usually has an excellent prognosis, no therapeutic options are available for patients that develop metastases and are or became resistant to radioiodine therapy. The deeper knowledge of molecular aberrations...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-009-0124-y

    authors: Capdevila J,Perez-Garcia J,Obiols G,Tabernero J

    更新日期:2009-12-01 00:00:00

  • Immunological Correlates of Response to Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma.

    abstract:BACKGROUND:The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions. OBJECTIVE:We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor ...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-018-0595-9

    authors: Tzeng A,Diaz-Montero CM,Rayman PA,Kim JS,Pavicic PG Jr,Finke JH,Barata PC,Lamenza M,Devonshire S,Schach K,Emamekhoo H,Ernstoff MS,Hoimes CJ,Rini BI,Garcia JA,Gilligan TD,Ornstein MC,Grivas P

    更新日期:2018-10-01 00:00:00

  • Expression and activity of EGFR in human cutaneous melanoma cell lines and influence of vemurafenib on the EGFR pathway.

    abstract::Data regarding the expression of epidermal growth factor receptor (EGFR) in melanoma and its role in the tumor biology are conflicting. In BRAF V600-mutant melanomas, the expression of EGFR has been associated with acquired resistance to BRAF inhibitors. In this study, we assessed EGFR expression and downstream signal...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-014-0318-9

    authors: Gross A,Niemetz-Rahn A,Nonnenmacher A,Tucholski J,Keilholz U,Fusi A

    更新日期:2015-03-01 00:00:00

  • Cardiovascular toxicities: clues to optimal administration of vascular endothelial growth factor signaling pathway inhibitors.

    abstract::Several angiogenesis inhibitors have been approved for commercial use and many additional agents are under development for the treatment of various malignancies. Cardiovascular toxicities have been increasingly recognized as effects of this entire class of new anticancer therapeutics. There is a limited but growing un...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-009-0106-0

    authors: Snider KL,Maitland ML

    更新日期:2009-04-01 00:00:00

  • Chronic therapy in gastrointestinal stromal tumours (GISTs): the big gap between theory and practice.

    abstract::The advent of imatinib mesilate, an oral target therapy, has dramatically changed the natural history of gastrointestinal stromal tumours (GISTs). This rare neoplasm has become the paradigm of targeted therapies in solid tumours, also introducing a home-based cure concept in oncology. However, it should be retained th...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-012-0221-1

    authors: Saponara M,Pantaleo MA,Nannini M,Biasco G

    更新日期:2012-12-01 00:00:00

  • The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review.

    abstract::Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker a...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-018-0567-0

    authors: Nichetti F,Marra A,Corti F,Guidi A,Raimondi A,Prinzi N,de Braud F,Pusceddu S

    更新日期:2018-06-01 00:00:00

  • Low Baseline Serum Sodium Concentration Is Associated with Poor Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy.

    abstract:BACKGROUND:A consistent percentage of patients with metastatic non-small cell lung cancer (NSCLC) derives no or only marginal benefit from immunotherapy (IO). OBJECTIVE:Since serum sodium has been linked to both prognosis in NSCLC and modulation of immune cells activity, we aimed to assess the association between low ...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-018-0599-5

    authors: Fucà G,Galli G,Poggi M,Lo Russo G,Proto C,Imbimbo M,Vitali M,Ganzinelli M,Lanti C,Molino G,Stangoni F,Zilembo N,de Braud F,Garassino MC,Signorelli D

    更新日期:2018-12-01 00:00:00

  • Targeting Met and VEGFR Axis in Metastatic Castration-Resistant Prostate Cancer: 'Game Over'?

    abstract::Despite recent advances that have been made in the therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC), effective management of bone metastases remains a key goal not yet reached. The receptor tyrosine kinase MET and the vascular endothelial growth factor receptor (VEGFR) seem to play an i...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-015-0412-7

    authors: Modena A,Massari F,Ciccarese C,Brunelli M,Santoni M,Montironi R,Martignoni G,Tortora G

    更新日期:2016-08-01 00:00:00

  • Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma.

    abstract::Obinutuzumab (Gazyva®, Gazyvaro®) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-017-0485-6

    authors: Dhillon S

    更新日期:2017-04-01 00:00:00

  • Effect of Renal Impairment on the Pharmacokinetics and Safety of Axitinib.

    abstract:BACKGROUND:Axitinib, an inhibitor of vascular endothelial growth factor (VEGF) receptors, is approved as second-line treatment for advanced renal cell carcinoma (RCC). Agents targeting the VEGF pathway may induce renal toxicities, which may be influenced by pre-existing renal dysfunction. OBJECTIVE:The objective was t...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-015-0389-2

    authors: Chen Y,Rini BI,Motzer RJ,Dutcher JP,Rixe O,Wilding G,Stadler WM,Tarazi J,Garrett M,Pithavala YK

    更新日期:2016-04-01 00:00:00

  • Impact of biomarkers on non-small cell lung cancer treatment.

    abstract::Chemotherapy represents the mainstay of non-small cell lung cancer (NSCLC) treatment, but response is usually observed in only one out of three patients. Massive efforts have been carried out to identify biomarkers that might help clinicians to choose appropriate drugs, by identifying potentially sensitive subjects an...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-010-0132-y

    authors: Toschi L,Cappuzzo F

    更新日期:2010-03-01 00:00:00

  • QTc prolongation induced by targeted biotherapies used in clinical practice and under investigation: a comprehensive review.

    abstract::In anticancer drug development, there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessmen...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-014-0325-x

    authors: Locatelli M,Criscitiello C,Esposito A,Minchella I,Goldhirsch A,Cipolla C,Curigliano G

    更新日期:2015-03-01 00:00:00

  • Impact of the Neutrophil-to-Lymphocyte Ratio on the Survival of Patients with Gastric Cancer Treated with Nivolumab Monotherapy.

    abstract:BACKGROUND:In 2017, nivolumab monotherapy was shown to be effective as third- or later-line therapy in patients with advanced gastric or gastroesophageal junction cancer. OBJECTIVE:In this study, we investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the outcomes of nivolumab monotherapy...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-020-00716-y

    authors: Yamada T,Hayashi T,Inokuchi Y,Hayashi K,Watanabe H,Komori K,Kano K,Shimoda Y,Fujikawa H,Shiozawa M,Morinaga S,Rino Y,Masuda M,Ogata T,Oshima T

    更新日期:2020-06-01 00:00:00

  • Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter, Retrospective Analysis by the MITO Group (MITO 24).

    abstract:BACKGROUND:The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking. OBJECTIVE:The MITO group conducted a...

    journal_title:Targeted oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s11523-018-0574-1

    authors: Farolfi A,Petrone M,Scarpi E,Gallà V,Greco F,Casanova C,Longo L,Cormio G,Orditura M,Bologna A,Zavallone L,Ventriglia J,Franzese E,Loizzi V,Giardina D,Pigozzi E,Cioffi R,Pignata S,Giorda G,De Giorgi U

    更新日期:2018-08-01 00:00:00

  • Renal Toxicities of Targeted Therapies.

    abstract::With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal tox...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-015-0368-7

    authors: Abbas A,Mirza MM,Ganti AK,Tendulkar K

    更新日期:2015-12-01 00:00:00

  • Imaging response in neuroendocrine tumors treated with targeted therapies: the experience of sunitinib.

    abstract::Among neuroendocrine carcinomas of the gut, well-differentiated tumors are highly vascularized, featuring specific characteristics on contrast-enhanced imaging. Well-differentiated neuroendocrine tumors spontaneously harbor hypervascular enhancement, coexisting with areas of necrosis mainly located at the center of tu...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-012-0216-y

    authors: Faivre S,Ronot M,Dreyer C,Serrate C,Hentic O,Bouattour M,Bruno O,Couvelard A,Vilgrain V,Raymond E

    更新日期:2012-06-01 00:00:00

  • Targeting multiple oncogenic pathways for the treatment of hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer diagnosed worldwide. HCC occurs due to chronic liver disease and is often diagnosed at advanced stages. Chemotherapeutic agents such as doxorubicin are currently used as first-line agents for HCC therapy, but these are non-selective cytotox...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-016-0452-7

    authors: Swamy SG,Kameshwar VH,Shubha PB,Looi CY,Shanmugam MK,Arfuso F,Dharmarajan A,Sethi G,Shivananju NS,Bishayee A

    更新日期:2017-02-01 00:00:00

  • Combinatorial Study of a Novel Poly (ADP-ribose) Polymerase Inhibitor and an HDAC Inhibitor, SAHA, in Leukemic Cell Lines.

    abstract:BACKGROUND:Cancer is a multifactorial disease, which makes it difficult to cure. Since more than one defective cellular component is often involved during oncogenesis, combination therapy is gaining prominence in the field of cancer therapeutics. OBJECTIVE:The purpose of this study was to investigate the combinatorial...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-016-0441-x

    authors: Hegde M,Mantelingu K,Pandey M,Pavankumar CS,Rangappa KS,Raghavan SC

    更新日期:2016-10-01 00:00:00

  • Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment.

    abstract::Dynamic contrast-enhanced ultrasonography (DCE-US) is a new functional technique enabling a quantitative assessment of solid tumor perfusion using raw linear data. DCE-US allows the calculation of parameters as slope of wash-in or area under the curve (AUC) representing, respectively, blood flow or blood volume. Reduc...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-010-0136-7

    authors: Lassau N,Chebil M,Chami L,Bidault S,Girard E,Roche A

    更新日期:2010-03-01 00:00:00

  • Gastric Inflammatory Prognostic Index (GIPI) in Patients with Metastatic Gastro-Esophageal Junction/Gastric Cancer Treated with PD-1/PD-L1 Immune Checkpoint Inhibitors.

    abstract:BACKGROUND:Immune checkpoint inhibitors (ICIs) demonstrated improved overall survival (OS) in heavily pretreated unselected patients with metastatic gastro-esophageal junction (mGOJ)/gastric cancer (GC). Attempts to select patients based on programmed death-ligand 1 (PD-L1) expression appear to be suboptimal. A strong ...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-020-00723-z

    authors: Formica V,Morelli C,Patrikidou A,Murias C,Butt S,Nardecchia A,Lucchetti J,Renzi N,Shiu KK,Roselli M,Arkenau HT

    更新日期:2020-06-01 00:00:00

  • Delta-catenin promotes the proliferation and invasion of colorectal cancer cells by binding to E-cadherin in a competitive manner with p120 catenin.

    abstract::δ-Catenin is the only member of the p120 catenin (p120ctn) subfamily whose normal pattern of expression is restricted to the brain. Similar to p120ctn, δ-catenin can bind to the juxtamembrane domain of E-cadherin. We examined the expression of δ-catenin, p120ctn, and E-cadherin using immunohistochemistry in 95 cases o...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-013-0269-6

    authors: Zhang H,Dai SD,Zhang D,Liu D,Zhang FY,Zheng TY,Cui MM,Dai CL

    更新日期:2014-03-01 00:00:00

  • Identification of driver mutations in lung cancer: first step in personalized cancer.

    abstract::Non-small cell lung cancer (NSCLC) has recently been associated with interesting molecular characteristics that have important implications in carcinogenesis and response to targeted therapies. Targeted therapies, if given to a patient subpopulation enriched by the presence of relevant molecular targets, can often abr...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-013-0263-z

    authors: Planchard D

    更新日期:2013-03-01 00:00:00

  • Activity and safety of erlotinib as second- and third-line treatment in elderly patients with advanced non-small cell lung cancer: a phase II trial.

    abstract::Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Efficacy of this drug was documented in the BR.21 trial showing that adenocarcinoma, female gender, Asian ethnicity and never-smoker status are predictive of clinical response to erlotinib. Retrospective studies documented the same bene...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-010-0163-4

    authors: Rossi D,Dennetta D,Ugolini M,Catalano V,Alessandroni P,Giordani P,Baldelli AM,Casadei V,Graziano F,Luzi Fedeli S

    更新日期:2010-12-01 00:00:00

  • Pralatrexate in Chinese Patients with Relapsed or Refractory Peripheral T-cell Lymphoma: A Single-arm, Multicenter Study.

    abstract:BACKGROUND:Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL. OBJECTIVE:As the distribution of PTCL subtypes differs between populations and few p...

    journal_title:Targeted oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s11523-019-00630-y

    authors: Hong X,Song Y,Huang H,Bai B,Zhang H,Ke X,Shi Y,Zhu J,Lu G,Liebscher S,Cai C

    更新日期:2019-04-01 00:00:00

  • Ongoing Response in BRAF V600E-Mutant Melanoma After Cessation of Intermittent Vemurafenib Therapy: A Case Report.

    abstract::The selective BRAF inhibitors vemurafenib and dabrafenib yield high response rates and improved overall survival in patients with BRAF V600E-mutant metastatic melanoma. Treatment traditionally continues until disease progression or the development of unacceptable toxicity. Acquired drug resistance and toxicity are key...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-015-0410-9

    authors: Dooley AJ,Gupta A,Middleton MR

    更新日期:2016-08-01 00:00:00

  • Serum Alpha1-Globulin as a Novel Prognostic Factor in Metastatic Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors.

    abstract:BACKGROUND:Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown. OBJECTIVE:We conducted this study to explore the prognostic value of SPF in patient...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-019-00625-9

    authors: Chen X,Yao J,Liu L,Zheng W,Hu X,Zhu Y,Wang H,Guo J

    更新日期:2019-04-01 00:00:00

  • A bispecific EpCAM/CD133-targeted toxin is effective against carcinoma.

    abstract::The discovery of chemoresistant cancer stem cells (CSCs) in carcinomas has created the need for therapies that specifically target these subpopulations of cells. Here, we characterized a bispecific targeted toxin that is composed of two antibody fragments and a catalytic protein toxin allowing it to bind two CSC marke...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-013-0290-9

    authors: Waldron NN,Barsky SH,Dougherty PR,Vallera DA

    更新日期:2014-09-01 00:00:00

  • The Multifaceted Roles of B Cells in Solid Tumors: Emerging Treatment Opportunities.

    abstract::The influence of tumor infiltrating lymphocytes on tumor growth and response to therapy is becoming increasingly apparent. While much work has focused on the role of T cell responses in anti-tumor immunity, the role of B cells in solid tumors is much less understood. Tumor infiltrating B cells have been found in a var...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-017-0481-x

    authors: Flynn NJ,Somasundaram R,Arnold KM,Sims-Mourtada J

    更新日期:2017-04-01 00:00:00