Loading…
AKT in cancer: new molecular insights and advances in drug development
The phosphatidylinositol‐3 kinase (PI3K)–AKT pathway is one of the most commonly dysregulated pathways in all of cancer, with somatic mutations, copy number alterations, aberrant epigenetic regulation and increased expression in a number of cancers. The carefully maintained homeostatic balance of ce...
Saved in:
| Published in: | British journal of clinical pharmacology 2016-10, Vol.82 (4), p.943-956 |
|---|---|
| Main Authors: | , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c4811-d1d9a20414ee2e4fa1199acc02eee6885f94d5dac56e57b04b8bcef326c655b63 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c4811-d1d9a20414ee2e4fa1199acc02eee6885f94d5dac56e57b04b8bcef326c655b63 |
| container_end_page | 956 |
| container_issue | 4 |
| container_start_page | 943 |
| container_title | British journal of clinical pharmacology |
| container_volume | 82 |
| creator | Mundi, Prabhjot S. Sachdev, Jasgit McCourt, Carolyn Kalinsky, Kevin |
| description | The phosphatidylinositol‐3 kinase (PI3K)–AKT pathway is one of the most commonly dysregulated pathways in all of cancer, with somatic mutations, copy number alterations, aberrant epigenetic regulation and increased expression in a number of cancers. The carefully maintained homeostatic balance of cell division and growth on one hand, and programmed cell death on the other, is universally disturbed in tumorigenesis, and downstream effectors of the PI3K–AKT pathway play an important role in this disturbance. With a wide array of downstream effectors involved in cell survival and proliferation, the well‐characterized direct interactions of AKT make it a highly attractive yet elusive target for cancer therapy. Here, we review the salient features of this pathway, evidence of its role in promoting tumorigenesis and recent progress in the development of therapeutic agents that target AKT. |
| doi_str_mv | 10.1111/bcp.13021 |
| format | article |
| fullrecord | <record><control><sourceid>wiley_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5137819</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>BCP13021</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4811-d1d9a20414ee2e4fa1199acc02eee6885f94d5dac56e57b04b8bcef326c655b63</originalsourceid><addsrcrecordid>eNp1kD1PwzAQhi0EoqUw8AdQVoa0Pjt2EgYkqCggKsFQZsuxL21QmkR2P9R_T0qggoFbbnife056CbkEOoR2RplphsApgyPSBy5FyICJY9KnnMpQMAE9cub9B6XAQYpT0mMx4ywRcZ9M7l5mQVEFRlcG3U1Q4TZY1iWadaldG_hivlj5QFc20Hazh_wet249DyxusKybJVarc3KS69LjxfcekPfJw2z8FE5fH5_Hd9PQRAlAaMGmmtEIIkSGUa4B0lQbQxkiyiQReRpZYbUREkWc0ShLMoM5Z9JIITLJB-S28zbrbInWtK-dLlXjiqV2O1XrQv1NqmKh5vVGCeBxAmkruO4ExtXeO8wPt0DVvkzVlqm-ymzZq9_PDuRPey0w6oBtUeLuf5O6H791yk-MW3-C</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>AKT in cancer: new molecular insights and advances in drug development</title><source>Wiley-Blackwell Read & Publish Collection</source><creator>Mundi, Prabhjot S. ; Sachdev, Jasgit ; McCourt, Carolyn ; Kalinsky, Kevin</creator><creatorcontrib>Mundi, Prabhjot S. ; Sachdev, Jasgit ; McCourt, Carolyn ; Kalinsky, Kevin</creatorcontrib><description>The phosphatidylinositol‐3 kinase (PI3K)–AKT pathway is one of the most commonly dysregulated pathways in all of cancer, with somatic mutations, copy number alterations, aberrant epigenetic regulation and increased expression in a number of cancers. The carefully maintained homeostatic balance of cell division and growth on one hand, and programmed cell death on the other, is universally disturbed in tumorigenesis, and downstream effectors of the PI3K–AKT pathway play an important role in this disturbance. With a wide array of downstream effectors involved in cell survival and proliferation, the well‐characterized direct interactions of AKT make it a highly attractive yet elusive target for cancer therapy. Here, we review the salient features of this pathway, evidence of its role in promoting tumorigenesis and recent progress in the development of therapeutic agents that target AKT.</description><identifier>ISSN: 0306-5251</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1111/bcp.13021</identifier><identifier>PMID: 27232857</identifier><language>eng</language><publisher>England: John Wiley and Sons Inc</publisher><subject>Animals ; Carcinogenesis - drug effects ; clinical oncology ; Humans ; medical oncology ; Molecular Targeted Therapy - methods ; Neoplasms - drug therapy ; Neoplasms - enzymology ; Neoplasms - metabolism ; Neoplasms - pathology ; Phosphatidylinositol 3-Kinases - physiology ; phosphatidylinositol 3‐kinases ; protein kinase B ; Proto-Oncogene Mas ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - physiology ; proto‐oncogene proteins c‐AKT ; proto‐oncogene proteins c‐AKT/genetics ; proto‐oncogene proteins c‐AKT/metabolism ; Review ; Reviews ; Signal Transduction - drug effects ; signal transduction/physiology</subject><ispartof>British journal of clinical pharmacology, 2016-10, Vol.82 (4), p.943-956</ispartof><rights>2016 The British Pharmacological Society</rights><rights>2016 The British Pharmacological Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4811-d1d9a20414ee2e4fa1199acc02eee6885f94d5dac56e57b04b8bcef326c655b63</citedby><cites>FETCH-LOGICAL-c4811-d1d9a20414ee2e4fa1199acc02eee6885f94d5dac56e57b04b8bcef326c655b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27232857$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mundi, Prabhjot S.</creatorcontrib><creatorcontrib>Sachdev, Jasgit</creatorcontrib><creatorcontrib>McCourt, Carolyn</creatorcontrib><creatorcontrib>Kalinsky, Kevin</creatorcontrib><title>AKT in cancer: new molecular insights and advances in drug development</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>The phosphatidylinositol‐3 kinase (PI3K)–AKT pathway is one of the most commonly dysregulated pathways in all of cancer, with somatic mutations, copy number alterations, aberrant epigenetic regulation and increased expression in a number of cancers. The carefully maintained homeostatic balance of cell division and growth on one hand, and programmed cell death on the other, is universally disturbed in tumorigenesis, and downstream effectors of the PI3K–AKT pathway play an important role in this disturbance. With a wide array of downstream effectors involved in cell survival and proliferation, the well‐characterized direct interactions of AKT make it a highly attractive yet elusive target for cancer therapy. Here, we review the salient features of this pathway, evidence of its role in promoting tumorigenesis and recent progress in the development of therapeutic agents that target AKT.</description><subject>Animals</subject><subject>Carcinogenesis - drug effects</subject><subject>clinical oncology</subject><subject>Humans</subject><subject>medical oncology</subject><subject>Molecular Targeted Therapy - methods</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - enzymology</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Phosphatidylinositol 3-Kinases - physiology</subject><subject>phosphatidylinositol 3‐kinases</subject><subject>protein kinase B</subject><subject>Proto-Oncogene Mas</subject><subject>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - physiology</subject><subject>proto‐oncogene proteins c‐AKT</subject><subject>proto‐oncogene proteins c‐AKT/genetics</subject><subject>proto‐oncogene proteins c‐AKT/metabolism</subject><subject>Review</subject><subject>Reviews</subject><subject>Signal Transduction - drug effects</subject><subject>signal transduction/physiology</subject><issn>0306-5251</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNp1kD1PwzAQhi0EoqUw8AdQVoa0Pjt2EgYkqCggKsFQZsuxL21QmkR2P9R_T0qggoFbbnife056CbkEOoR2RplphsApgyPSBy5FyICJY9KnnMpQMAE9cub9B6XAQYpT0mMx4ywRcZ9M7l5mQVEFRlcG3U1Q4TZY1iWadaldG_hivlj5QFc20Hazh_wet249DyxusKybJVarc3KS69LjxfcekPfJw2z8FE5fH5_Hd9PQRAlAaMGmmtEIIkSGUa4B0lQbQxkiyiQReRpZYbUREkWc0ShLMoM5Z9JIITLJB-S28zbrbInWtK-dLlXjiqV2O1XrQv1NqmKh5vVGCeBxAmkruO4ExtXeO8wPt0DVvkzVlqm-ymzZq9_PDuRPey0w6oBtUeLuf5O6H791yk-MW3-C</recordid><startdate>201610</startdate><enddate>201610</enddate><creator>Mundi, Prabhjot S.</creator><creator>Sachdev, Jasgit</creator><creator>McCourt, Carolyn</creator><creator>Kalinsky, Kevin</creator><general>John Wiley and Sons Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>201610</creationdate><title>AKT in cancer: new molecular insights and advances in drug development</title><author>Mundi, Prabhjot S. ; Sachdev, Jasgit ; McCourt, Carolyn ; Kalinsky, Kevin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4811-d1d9a20414ee2e4fa1199acc02eee6885f94d5dac56e57b04b8bcef326c655b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Carcinogenesis - drug effects</topic><topic>clinical oncology</topic><topic>Humans</topic><topic>medical oncology</topic><topic>Molecular Targeted Therapy - methods</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - enzymology</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Phosphatidylinositol 3-Kinases - physiology</topic><topic>phosphatidylinositol 3‐kinases</topic><topic>protein kinase B</topic><topic>Proto-Oncogene Mas</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - physiology</topic><topic>proto‐oncogene proteins c‐AKT</topic><topic>proto‐oncogene proteins c‐AKT/genetics</topic><topic>proto‐oncogene proteins c‐AKT/metabolism</topic><topic>Review</topic><topic>Reviews</topic><topic>Signal Transduction - drug effects</topic><topic>signal transduction/physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mundi, Prabhjot S.</creatorcontrib><creatorcontrib>Sachdev, Jasgit</creatorcontrib><creatorcontrib>McCourt, Carolyn</creatorcontrib><creatorcontrib>Kalinsky, Kevin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mundi, Prabhjot S.</au><au>Sachdev, Jasgit</au><au>McCourt, Carolyn</au><au>Kalinsky, Kevin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AKT in cancer: new molecular insights and advances in drug development</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>2016-10</date><risdate>2016</risdate><volume>82</volume><issue>4</issue><spage>943</spage><epage>956</epage><pages>943-956</pages><issn>0306-5251</issn><eissn>1365-2125</eissn><abstract>The phosphatidylinositol‐3 kinase (PI3K)–AKT pathway is one of the most commonly dysregulated pathways in all of cancer, with somatic mutations, copy number alterations, aberrant epigenetic regulation and increased expression in a number of cancers. The carefully maintained homeostatic balance of cell division and growth on one hand, and programmed cell death on the other, is universally disturbed in tumorigenesis, and downstream effectors of the PI3K–AKT pathway play an important role in this disturbance. With a wide array of downstream effectors involved in cell survival and proliferation, the well‐characterized direct interactions of AKT make it a highly attractive yet elusive target for cancer therapy. Here, we review the salient features of this pathway, evidence of its role in promoting tumorigenesis and recent progress in the development of therapeutic agents that target AKT.</abstract><cop>England</cop><pub>John Wiley and Sons Inc</pub><pmid>27232857</pmid><doi>10.1111/bcp.13021</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0306-5251 |
| ispartof | British journal of clinical pharmacology, 2016-10, Vol.82 (4), p.943-956 |
| issn | 0306-5251 1365-2125 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5137819 |
| source | Wiley-Blackwell Read & Publish Collection |
| subjects | Animals Carcinogenesis - drug effects clinical oncology Humans medical oncology Molecular Targeted Therapy - methods Neoplasms - drug therapy Neoplasms - enzymology Neoplasms - metabolism Neoplasms - pathology Phosphatidylinositol 3-Kinases - physiology phosphatidylinositol 3‐kinases protein kinase B Proto-Oncogene Mas Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - physiology proto‐oncogene proteins c‐AKT proto‐oncogene proteins c‐AKT/genetics proto‐oncogene proteins c‐AKT/metabolism Review Reviews Signal Transduction - drug effects signal transduction/physiology |
| title | AKT in cancer: new molecular insights and advances in drug development |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T18%3A36%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-wiley_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=AKT%20in%20cancer:%20new%20molecular%20insights%20and%20advances%20in%20drug%20development&rft.jtitle=British%20journal%20of%20clinical%20pharmacology&rft.au=Mundi,%20Prabhjot%20S.&rft.date=2016-10&rft.volume=82&rft.issue=4&rft.spage=943&rft.epage=956&rft.pages=943-956&rft.issn=0306-5251&rft.eissn=1365-2125&rft_id=info:doi/10.1111/bcp.13021&rft_dat=%3Cwiley_pubme%3EBCP13021%3C/wiley_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4811-d1d9a20414ee2e4fa1199acc02eee6885f94d5dac56e57b04b8bcef326c655b63%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/27232857&rfr_iscdi=true |