Heparanase and the hallmarks of cancer DOI Creative Commons

Krishnath M. Jayatilleke,

Mark D. Hulett

Journal of Translational Medicine, Journal Year: 2020, Volume and Issue: 18(1)

Published: Nov. 30, 2020

Abstract Heparanase is the only mammalian enzyme that cleaves heparan sulphate, an important component of extracellular matrix. This leads to remodelling matrix, whilst liberating growth factors and cytokines bound sulphate. in turn promotes both physiological pathological processes such as angiogenesis, immune cell migration, inflammation, wound healing metastasis. Furthermore, heparanase exhibits non-enzymatic actions signalling regulating gene expression. Cancer underpinned by key characteristic features promote malignant disease progression, collectively termed ‘hallmarks cancer’. Essentially, all cancers examined date have been reported overexpress heparanase, leading enhanced tumour metastasis with concomitant poor patient survival. With its multiple roles within microenvironment, has demonstrated regulate each these hallmark features, highlighting need for heparanase-targeted therapies. However, recent discoveries which can also vital anti-tumour mechanisms cast doubt on this approach. review will explore myriad ways functions a regulator hallmarks cancer highlight role major microenvironment. The dual however, emphasises further investigation into defining precise mechanism action different settings.

Language: Английский

Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity DOI Open Access
Shannon Lee, Jens Rauch, Walter Kölch

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(3), P. 1102 - 1102

Published: Feb. 7, 2020

Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous signal transduction that regulate all aspects of life and are frequently altered in disease. Here, we focus on the role MAPK modulating drug sensitivity resistance cancer. We briefly discuss new findings extracellular signaling-regulated (ERK) pathway, but mainly mechanisms how stress activated pathways, such as p38 Jun N-terminal kinases (JNK), impact response cancer cells to chemotherapies targeted therapies. In this context, also metabolic epigenetic aberrations therapeutic opportunities arising from these changes.

Language: Английский

Citations

637
Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways and targeted therapies DOI

Zhenyi An,

Ozlem Aksoy,

Tina Zheng

et al.

Oncogene, Journal Year: 2018, Volume and Issue: 37(12), P. 1561 - 1575

Published: Jan. 8, 2018

Language: Английский

Citations

512
How the Warburg effect supports aggressiveness and drug resistance of cancer cells? DOI
Philippe Icard,

S. Shulman,

Diana Farhat

et al.

Drug Resistance Updates, Journal Year: 2018, Volume and Issue: 38, P. 1 - 11

Published: March 20, 2018

Language: Английский

Citations

464
A history of exploring cancer in context DOI

Shelly Maman,

Isaac P. Witz

Nature reviews. Cancer, Journal Year: 2018, Volume and Issue: 18(6), P. 359 - 376

Published: April 26, 2018

Language: Английский

Citations

448
Molecular mechanisms for tumour resistance to chemotherapy DOI Open Access
Shuting Pan, Zhiling Li, Zhixu He

et al.

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2016, Volume and Issue: 43(8), P. 723 - 737

Published: April 21, 2016

Summary Chemotherapy is one of the prevailing methods used to treat malignant tumours, but outcome and prognosis tumour patients are not optimistic. Cancer cells gradually generate resistance almost all chemotherapeutic drugs via a variety distinct mechanisms pathways. Chemotherapeutic resistance, either intrinsic or acquired, caused sustained by reduced drug accumulation increased export, alterations in targets signalling transduction molecules, repair drug‐induced DNA damage, evasion apoptosis. In order better understand chemoresistance, this review highlights our current knowledge role altered metabolism transport deregulation apoptosis autophagy development chemoresistance. Reduced intracellular activation prodrugs (e.g. thiotepa tegafur) enhanced inactivation Phase I II enzymes contributes Both primary acquired can be anticancer which mediated transporters such as P‐glycoprotein (P‐gp), multidrug associated proteins, breast cancer protein. Presently there line evidence indicating that programmed cell death including also an important mechanism for drugs. Reversal chemoresistance likely pharmacological biological approaches. Further studies warranted grasp full picture how each type develop identify novel strategies overcome it.

Language: Английский

Citations

363
Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation DOI Creative Commons
Christopher J. Tape, Stephanie Ling, Maria Dimitriadi

et al.

Cell, Journal Year: 2016, Volume and Issue: 165(4), P. 910 - 920

Published: April 15, 2016

Highlights•KRASG12D establishes a reciprocal signaling axis via heterotypic stromal cells•Reciprocal further regulates tumor cell downstream of KRASG12D•Reciprocal behavior AXL/IGF1R-AKT•Heterocellularity expands beyond cell-autonomous pathwaysSummaryOncogenic mutations regulate within both cells and adjacent cells. Here, we show that oncogenic KRAS (KRASG12D) also By combining cell-specific proteome labeling with multivariate phosphoproteomics, analyzed heterocellular KRASG12D in pancreatic ductal adenocarcinoma (PDA) Tumor engages fibroblasts, which subsequently instigate the Reciprocal employs additional kinases doubles number regulated nodes from KRASG12D. Consequently, produces phosphoproteome total is distinct alone. proliferation apoptosis increases mitochondrial capacity an IGF1R/AXL-AKT axis. These results demonstrate oncogene should be viewed as process our existing perspective underrepresents extent cancer.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiIwYzlhZjIwYjU0ZDMyZDliNjcyNzU5NjkwMmExMWZlMiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNzI4MTUyNTkwfQ.j1jUow4SJ5n2kuOaT90PJ2nh7W8_-ovrr5IoTuWyTWnSEniGVZzjn2gBcKTTL4zPV4UA0q3VkXru2FibPxhf3SMm7oNRGfmfRs2RgNLMK7Bt3QlhtpR7MTBD3Pf4FVad1LXx-RNrDZGwFvQFSkn1Rz45LTpSb_d3nSM0PO8ICuvZk8fSgaEoEMZJKrJUWxY2pxZlWsg-jVCGGCNMWcYkzuWrEWm224eUZCo17yaB3hxY5LdoygyF6MrQmjxdE3_1KIBzsfKwAxTgqotxHB7fPiLGM8AEWAuEpmA6sXG7nQQbz1iKFwjekm1ZPI8Ymjd8TL4DSe6Aagy39aRO6IBJtADownload video (mp4, 36 MB)Graphical abstract

Language: Английский

Citations

342
Cyclin-dependent protein serine/threonine kinase inhibitors as anticancer drugs DOI
Robert Roskoski

Pharmacological Research, Journal Year: 2018, Volume and Issue: 139, P. 471 - 488

Published: Nov. 30, 2018

Language: Английский

Citations

327
Network biology concepts in complex disease comorbidities DOI

Jessica Xin Hu,

Cecilia Engel Thomas, Søren Brunak

et al.

Nature Reviews Genetics, Journal Year: 2016, Volume and Issue: 17(10), P. 615 - 629

Published: Aug. 8, 2016

Language: Английский

Citations

305
Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma DOI
Tiffany Tsang, Jessica M. Posimo,

A. Andrea Gudiel

et al.

Nature Cell Biology, Journal Year: 2020, Volume and Issue: 22(4), P. 412 - 424

Published: March 16, 2020

Language: Английский

Citations

283
Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy DOI Open Access
Donatella D’Eliseo, Francesca Velotti

Journal of Clinical Medicine, Journal Year: 2016, Volume and Issue: 5(2), P. 15 - 15

Published: Jan. 26, 2016

Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) docosahexaenoic (DHA), can exert anti-neoplastic activity inducing apoptotic cell death human either alone or combination with therapies. Indeed, PUFAs potentially increase the sensitivity therapies, possibly improving their efficacy especially against cancers resistant treatment. Moreover, contrast traditional appear cause selective cytotoxicity little no on This review focuses studies investigating via apoptosis, analyzing molecular mechanisms underlying this effective activity. Here, we highlight multiple molecules targeted trigger apoptosis. analysis allow better comprehension potential therapeutic role cancer, providing specific information support design future pre-clinical clinical for use combinational therapy.

Language: Английский

Citations

278