Selective Targeting of RSK Isoforms in Cancer.

Abstract:

:The p90 ribosomal S6 kinase family (RSK1-4) is a group of highly conserved Ser/Thr kinases that act as downstream effectors of the Ras/Raf/MEK/ERK signaling pathway. The RSKs phosphorylate a range of substrates involved in transcription, translation, cell cycle regulation, and cell survival. Although the RSKs have a high degree of sequence homology, their functional differences in cancer are of great interest. Current RSK inhibitors target more than one RSK isoform, and this may limit their efficacy as anticancer agents. Here, we review the structure and function of the RSK kinases, their role in cancer growth and survival, and their potential as modulators of chemoresistance. In addition, we summarize the development of current RSK inhibitors and their limitations.

journal_name

Trends Cancer

journal_title

Trends in cancer

authors

Casalvieri KA,Matheson CJ,Backos DS,Reigan P

doi

10.1016/j.trecan.2017.03.004

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

302-312

issue

4

eissn

2405-8033

issn

2405-8025

pii

S2405-8033(17)30059-6

journal_volume

3

pub_type

杂志文章,评审
  • The Role of Type 1 Conventional Dendritic Cells in Cancer Immunity.

    abstract::Dendritic cells (DCs) are key orchestrators of immune responses. A specific DC subset, conventional type 1 DCs (cDC1s), has been recently associated with human cancer patient survival and, in preclinical models, is critical for the spontaneous rejection of immunogenic cancers and for the success of T cell-based immuno...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2018.09.001

    authors: Böttcher JP,Reis e Sousa C

    更新日期:2018-11-01 00:00:00

  • Resistance to Ibrutinib in B Cell Malignancies: One Size Does Not Fit All.

    abstract::Ibrutinib resistance, as a result of coordinated rewiring of signaling networks and enforced tumor microenvironment (TME)-lymphoma interactions, drives unrestrained proliferation and disease progression. To combat resistance mechanisms, we must identify the compensatory resistance pathways and the central modulators o...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2018.01.004

    authors: Shah B,Zhao X,Silva AS,Shain KH,Tao J

    更新日期:2018-03-01 00:00:00

  • Nutrient Exploitation within the Tumor-Stroma Metabolic Crosstalk.

    abstract::The tumor microenvironment has an essential role in defining tumor malignancy, since it can either promote or prevent tumor initiation and subsequent progression and metastatic dissemination. Recent studies demonstrate that highly aggressive cancer cells display a high degree of metabolic plasticity paralleled by the ...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2016.11.001

    authors: Morandi A,Giannoni E,Chiarugi P

    更新日期:2016-12-01 00:00:00

  • Exons of Leukemia Suppressor Genes: Creative Assembly Required.

    abstract::Alternative splicing (AS) has many important roles in the pathogenesis of leukemia. Recent papers suggest that one of its key aspects is exclusion of 3'-terminal exons in favor of premature termination using intronic polyadenylation signals. This process generates leukemia suppressor isoforms with truncated C termini ...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2018.10.005

    authors: Asnani M,Thomas-Tikhonenko A

    更新日期:2018-12-01 00:00:00

  • Immune Checkpoint Inhibition in Prostate Cancer.

    abstract::Although immunotherapy has proved to be effective in a variety of cancer subtypes, the role of immune checkpoint inhibition in the treatment of prostate cancer remains unclear. Here we review results from the latest clinical trials and discuss data suggesting that certain genetic mutations may confer increased sensiti...

    journal_title:Trends in cancer

    pub_type: 杂志文章

    doi:10.1016/j.trecan.2020.01.003

    authors: Nicholson LT,Fong L

    更新日期:2020-03-01 00:00:00

  • Exit Stage Left: A Tumor Cell's Journey from Lymph Node to Beyond.

    abstract::Even though we have known for over 250 years that cancers spread to regional lymph nodes (LNs) and distant organs, the fundamental question of which anatomical routes are taken by tumor cells has remained a mystery. Two recently published papers in Science, by Pereira et al. and Brown et al., directly address this imp...

    journal_title:Trends in cancer

    pub_type: 评论,杂志文章

    doi:10.1016/j.trecan.2018.05.007

    authors: Achen MG,Stacker SA

    更新日期:2018-08-01 00:00:00

  • Cancer Genomics in Clinical Context.

    abstract::Precision medicine requires appropriate application of genomics in clinical practice. In cancer, we have witnessed practice-changing examples of how genomic knowledge is translated into more tailored and effective therapies. The next opportunity is to embed cancer genomics in clinical context so that patient-centric l...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2015.07.010

    authors: Chin L,Wargo JA,Spring DJ,Kantarjian H,Futreal PA

    更新日期:2015-09-01 00:00:00

  • Targeting Nuclear Receptors for Cancer Therapy: Premises, Promises, and Challenges.

    abstract::Nuclear receptors are a family of transcription factors localized in cell nuclei, sensing specific ligands and fine-tuning a variety of cell physiological events. They have been intensively investigated in cancer biology. With their excellent properties of druggability and actionability, nuclear receptors have demonst...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2020.11.007

    authors: Yang Z,Gimple RC,Zhou N,Zhao L,Gustafsson JÅ,Zhou S

    更新日期:2020-12-16 00:00:00

  • Lysophosphatidate Signaling: The Tumor Microenvironment's New Nemesis.

    abstract::Lysophosphatidate (LPA) is emerging as a potent mediator of cancer progression in the tumor microenvironment. Strategies for targeting LPA signaling have recently entered clinical trials for fibrosis. These therapies have potential to improve the efficacies of existing chemotherapies and radiotherapy by attenuating ch...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2017.09.004

    authors: Benesch MGK,Yang Z,Tang X,Meng G,Brindley DN

    更新日期:2017-11-01 00:00:00

  • Thermoneutrality, Mice, and Cancer: A Heated Opinion.

    abstract::The 'mild' cold stress caused by standard sub-thermoneutral housing temperatures used for laboratory mice in research institutes is sufficient to significantly bias conclusions drawn from murine models of several human diseases. We review the data leading to this conclusion, discuss the implications for research and s...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2016.03.005

    authors: Hylander BL,Repasky EA

    更新日期:2016-04-01 00:00:00

  • Cadherins Glycans in Cancer: Sweet Players in a Bitter Process.

    abstract::Cadherins are key components in tissue morphogenesis and architecture, contributing to the establishment of cohesive cell adhesion. Reduced cellular adhesiveness as a result of cadherin dysfunction is a defining feature of cancer. During tumor development and progression, major changes in the glycan repertoire of canc...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2016.08.003

    authors: Carvalho S,Reis CA,Pinho SS

    更新日期:2016-09-01 00:00:00

  • Targeting EMT in Cancer with Repurposed Metabolic Inhibitors.

    abstract::Epithelial-to-mesenchymal transition (EMT) determines the most lethal features of cancer, metastasis formation and chemoresistance, and therefore represents an attractive target in oncology. However, direct targeting of EMT effector molecules is, in most cases, pharmacologically challenging. Since emerging research ha...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2020.06.005

    authors: Ramesh V,Brabletz T,Ceppi P

    更新日期:2020-11-01 00:00:00

  • Challenging Standard-of-Care Paradigms in the Precision Oncology Era.

    abstract::The pace of genomic and immunological breakthroughs in oncology is accelerating, making it likely that large randomized trials will increasingly become outdated before their completion. Traditional clinical research/practice paradigms must adapt to the reality unveiled by genomics, especially the need for customized d...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2017.12.004

    authors: Subbiah V,Kurzrock R

    更新日期:2018-02-01 00:00:00

  • Connecting Timescales in Biology: Can Early Dynamical Measurements Predict Long-Term Outcomes?

    abstract::Prediction of long-term outcomes from short-term measurements remains a fundamental challenge. Quantitative assessment of signaling dynamics, and the resulting transcriptomic and proteomic responses, has yielded fundamental insights into cellular outcomes. However, the utility of these measurements is limited by their...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2020.12.008

    authors: Tsabar M,Lovitch SB,Jambhekar A,Lahav G

    更新日期:2021-01-12 00:00:00

  • Born to Kill: NK Cells Go to War against Cancer.

    abstract::Preclinical and clinical data emerging over the past year demonstrate that cancer cells suppress the cytotoxic functions of natural killer cells by a variety of mechanisms. These findings reveal a new arsenal of actionable therapeutic targets to drive clinically relevant immune responses against cancer. ...

    journal_title:Trends in cancer

    pub_type: 信件

    doi:10.1016/j.trecan.2018.12.005

    authors: Wennerberg E,Galluzzi L

    更新日期:2019-03-01 00:00:00

  • Assessing Novel Therapies Based on Late-Stage Efficacy: A Dangerous Concept?

    abstract::Traditionally, the efficacy of novel cancer therapies has been confirmed in patients failing regular treatment before being tested in early disease. Improved understanding of the mechanisms guiding therapeutic efficacy may challenge this dogma, suggesting novel therapies to move into early evaluation based on biologic...

    journal_title:Trends in cancer

    pub_type: 杂志文章

    doi:10.1016/j.trecan.2020.11.010

    authors: Lønning PE

    更新日期:2020-12-22 00:00:00

  • Turning Cold into Hot: Firing up the Tumor Microenvironment.

    abstract::Cancers develop within complex tissue environments consisting of diverse innate and adaptive immune cells, along with stromal cells, vascular networks, and many other cellular and noncellular components. The high heterogeneity within the tumor microenvironment (TME) remains a key obstacle in understanding and treating...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2020.02.022

    authors: Duan Q,Zhang H,Zheng J,Zhang L

    更新日期:2020-07-01 00:00:00

  • Emerging Players in Prostate Cancer-Bone Niche Communication.

    abstract::Patients with advanced prostate cancer (PCa) frequently develop skeletal metastases that are associated with fractures, disability, and increased mortality. Within the bone metastatic niche, mutual interactions between tumor cells and osteoblasts have been proposed as major contributors of osteotropism by PCa. Here, w...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2020.09.006

    authors: Furesi G,Rauner M,Hofbauer LC

    更新日期:2021-02-01 00:00:00

  • Noninvasive PET Imaging of T cells.

    abstract::The rapidly evolving field of cancer immunotherapy recently saw the approval of several new therapeutic antibodies. Several cell therapies, for example, chimeric antigen receptor-expressing T cells (CAR-T), are currently in clinical trials for a variety of cancers and other diseases. However, approaches to monitor cha...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2018.03.009

    authors: Wei W,Jiang D,Ehlerding EB,Luo Q,Cai W

    更新日期:2018-05-01 00:00:00

  • Emerging role of mTOR in the response to cancer therapeutics.

    abstract::The movement toward precision medicine with targeted therapeutics for cancer treatment has been hindered by both innate and acquired resistance. Understanding the molecular wiring and plasticity of oncogenic signaling networks is essential to the development of therapeutic strategies to avoid or overcome resistance. T...

    journal_title:Trends in cancer

    pub_type: 杂志文章

    doi:10.1016/j.trecan.2016.03.008

    authors: Ilagan E,Manning BD

    更新日期:2016-05-01 00:00:00

  • Repurposing Drugs in Oncology: Next Steps.

    abstract::The repurposing of existing non-cancer drugs is a potential source of new treatment options for cancer patients with high unmet medical needs. While scientific research is progressing rapidly in the field of drug repurposing, the implementation of drug repurposing still faces important financial and regulatory hurdles...

    journal_title:Trends in cancer

    pub_type: 杂志文章

    doi:10.1016/j.trecan.2017.06.007

    authors: Verbaanderd C,Meheus L,Huys I,Pantziarka P

    更新日期:2017-08-01 00:00:00

  • DUBs, Hypoxia, and Cancer.

    abstract::Alterations in protein ubiquitylation and hypoxia are commonly associated with cancer. Ubiquitylation is carried out by three sequentially acting ubiquitylating enzymes and can be opposed by deubiquitinases (DUBs), which have emerged as promising drug targets. Apart from protein localization and activity, ubiquitylati...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2019.08.005

    authors: Mennerich D,Kubaichuk K,Kietzmann T

    更新日期:2019-10-01 00:00:00

  • Cancer of Unknown Primary in the Molecular Era.

    abstract::Cancer of unknown primary (CUP) is a rare malignancy that presents with metastatic disease and no identifiable site of origin. Most patients have unfavorable features and attempts to treat based on tissue-of-origin identification have not yielded a survival advantage compared with empiric chemotherapy. Next-generation...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2020.11.002

    authors: Kato S,Alsafar A,Walavalkar V,Hainsworth J,Kurzrock R

    更新日期:2021-01-27 00:00:00

  • The Emerging Role of ABL Kinases in Solid Tumors.

    abstract::The Abelson (ABL) tyrosine kinases were identified as drivers of leukemia in mice and humans. Emerging data has shown a role for the ABL family kinases, ABL1 and ABL2, in the progression of several solid tumors. This review will focus on recent reports of the involvement of the ABL kinases in tumor progression using m...

    journal_title:Trends in cancer

    pub_type: 杂志文章

    doi:10.1016/j.trecan.2015.07.004

    authors: Wang J,Pendergast AM

    更新日期:2015-10-01 00:00:00

  • Cirrhosis: A Questioned Risk Factor for Hepatocellular Carcinoma.

    abstract::The liver is one of the major metabolic organs in the body, susceptible to injury caused by various factors. In response to injury, sophisticated mechanisms are engaged to repair and regenerate the damaged liver, preventing its failure. When the damage is chronic, regeneration goes awry, impairing liver function and c...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2020.08.005

    authors: Garrido A,Djouder N

    更新日期:2021-01-01 00:00:00

  • Liquid Biopsies in Colorectal Cancer: Monitoring Genetic Heterogeneity.

    abstract::Dynamic changes in the colorectal cancer (CRC) signalome and tumor genetic heterogeneity underlie acquired drug resistance. Improving treatment-related decisions is facilitated by an emerging consensus in the classification of tumor subtypes as well as by real-time monitoring of predictive biomarkers in circulating tu...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2017.01.003

    authors: Gargalionis AN,Papavassiliou AG

    更新日期:2017-03-01 00:00:00

  • Advanced Prostate Cancer: Treatment Advances and Future Directions.

    abstract::Prostate cancer affects one in every nine men in the USA and is the second leading cause of cancer-related death. The treatment landscape of advanced prostate cancer is changing rapidly. Multiple agents including abiraterone, enzalutamide, apalutamide, darolutamide, docetaxel, cabazitaxel, radium-223, and sipuleucel-T...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2020.04.010

    authors: Swami U,McFarland TR,Nussenzveig R,Agarwal N

    更新日期:2020-08-01 00:00:00

  • In Vivo RNAi Screening for Pancreatic Cancer Drivers: PILOTing the WDR5-MYC Axis.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) represents a major global health problem that causes over 200000 deaths each year worldwide. The disease is highly resistant to cytotoxic and targeted therapies and the average survival is less than 12 months. This situation prompted Alessandro Carugo and Giulio Draetta to devel...

    journal_title:Trends in cancer

    pub_type: 评论,杂志文章

    doi:10.1016/j.trecan.2016.07.002

    authors: Schneider G,Saur D

    更新日期:2016-08-01 00:00:00

  • Compromised Telomeric Heterochromatin Promotes ALTernative Lengthening of Telomeres.

    abstract::Alternative lengthening of telomeres (ALT) is an enigmatic process that allows certain cancers to maintain telomeres in the absence of telomerase. ALT cancers are frequently defective for ATRX/DAXX, a chaperone complex that deposits histone variant H3.3 at telomeres. We propose that mutations in alpha thalassemia-ment...

    journal_title:Trends in cancer

    pub_type: 杂志文章

    doi:10.1016/j.trecan.2016.02.003

    authors: Voon HPJ,Collas P,Wong LH

    更新日期:2016-03-01 00:00:00

  • Mitochondrial DNA Haplotypes as Genetic Modifiers of Cancer.

    abstract::Mitochondria play an essential role in cellular metabolism, generation of reactive oxygen species (ROS), and the initiation of apoptosis. These properties enable mitochondria to be crucial integrators in the pathways of tumorigenesis. An open question is to what extent variation in the mitochondrial genome (mtDNA) con...

    journal_title:Trends in cancer

    pub_type: 杂志文章,评审

    doi:10.1016/j.trecan.2020.08.004

    authors: Tasdogan A,McFadden DG,Mishra P

    更新日期:2020-12-01 00:00:00