Potential therapeutics using tumor-secreted lactate in nonsmall cell lung cancer
•Non-small cell lung cancer (NSCLC) frequently presents genetic mutuations.•NSCLC upregulates glucose metabolism and subsequent accumulates lactate.•Lactate as key molecule leads various phenomena in tumor microenvironment.•Lactate oxidase (LOX) can directly oxidize tumor-secreted lactate.•Consuming...
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| Veröffentlicht in: | Drug discovery today 2021-11, Vol.26 (11), p.2508-2514 |
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| creator | Liao, Zi-Xian Kempson, Ivan M. Hsieh, Chia-Chen Tseng, S.-Ja Yang, Pan-Chyr |
| description | •Non-small cell lung cancer (NSCLC) frequently presents genetic mutuations.•NSCLC upregulates glucose metabolism and subsequent accumulates lactate.•Lactate as key molecule leads various phenomena in tumor microenvironment.•Lactate oxidase (LOX) can directly oxidize tumor-secreted lactate.•Consuming or oxidizing tumor-secreted lactate provides a potential route.
Targeted-therapy failure in treating nonsmall cell lung cancer (NSCLC) frequently occurs because of the emergence of drug resistance and genetic mutations. The same mutations also result in aerobic glycolysis, which further antagonizes outcomes by localized increases in lactate, an immune suppressor. Recent evidence indicates that enzymatic lowering of lactate can promote an oncolytic immune microenvironment within the tumour. Here, we review factors relating to lactate expression in NSCLC and the utility of lactate oxidase (LOX) for governing therapeutic delivery, its role in lactate oxidation and turnover, and relationships between lactate depletion and immune cell populations. The lactate-rich characteristic of NSCLC provides an exploitable property to potentially improve NSCLC outcomes and design new therapeutic strategies to integrate with conventional therapies. |
| doi_str_mv | 10.1016/j.drudis.2021.07.014 |
| format | Article |
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Targeted-therapy failure in treating nonsmall cell lung cancer (NSCLC) frequently occurs because of the emergence of drug resistance and genetic mutations. The same mutations also result in aerobic glycolysis, which further antagonizes outcomes by localized increases in lactate, an immune suppressor. Recent evidence indicates that enzymatic lowering of lactate can promote an oncolytic immune microenvironment within the tumour. Here, we review factors relating to lactate expression in NSCLC and the utility of lactate oxidase (LOX) for governing therapeutic delivery, its role in lactate oxidation and turnover, and relationships between lactate depletion and immune cell populations. The lactate-rich characteristic of NSCLC provides an exploitable property to potentially improve NSCLC outcomes and design new therapeutic strategies to integrate with conventional therapies.</description><identifier>ISSN: 1359-6446</identifier><identifier>EISSN: 1878-5832</identifier><identifier>DOI: 10.1016/j.drudis.2021.07.014</identifier><identifier>PMID: 34325010</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anaplastic Lymphoma Kinase - genetics ; Animals ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Citric Acid Cycle ; Drug Resistance, Neoplasm ; Genes, erbB-1 - genetics ; Glucose - metabolism ; Humans ; Immune Checkpoint Inhibitors - therapeutic use ; L-Lactate Dehydrogenase - antagonists & inhibitors ; Lactate ; Lactate oxidase ; Lactic Acid - metabolism ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Metabolic Networks and Pathways ; Mixed Function Oxygenases - therapeutic use ; Molecular Targeted Therapy ; Nanoparticles ; Nonsmall cell lung cancer ; NSCLC ; Protein Kinase Inhibitors - therapeutic use ; Proto-Oncogene Proteins p21(ras) - genetics ; Tumor Microenvironment</subject><ispartof>Drug discovery today, 2021-11, Vol.26 (11), p.2508-2514</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-5019da57318b7aefab64a3b2768d366dd693277ca91f9535d748e51dd7b7ed343</citedby><cites>FETCH-LOGICAL-c362t-5019da57318b7aefab64a3b2768d366dd693277ca91f9535d748e51dd7b7ed343</cites><orcidid>0000-0001-6521-7620 ; 0000-0002-1299-7202</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.drudis.2021.07.014$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34325010$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liao, Zi-Xian</creatorcontrib><creatorcontrib>Kempson, Ivan M.</creatorcontrib><creatorcontrib>Hsieh, Chia-Chen</creatorcontrib><creatorcontrib>Tseng, S.-Ja</creatorcontrib><creatorcontrib>Yang, Pan-Chyr</creatorcontrib><title>Potential therapeutics using tumor-secreted lactate in nonsmall cell lung cancer</title><title>Drug discovery today</title><addtitle>Drug Discov Today</addtitle><description>•Non-small cell lung cancer (NSCLC) frequently presents genetic mutuations.•NSCLC upregulates glucose metabolism and subsequent accumulates lactate.•Lactate as key molecule leads various phenomena in tumor microenvironment.•Lactate oxidase (LOX) can directly oxidize tumor-secreted lactate.•Consuming or oxidizing tumor-secreted lactate provides a potential route.
Targeted-therapy failure in treating nonsmall cell lung cancer (NSCLC) frequently occurs because of the emergence of drug resistance and genetic mutations. The same mutations also result in aerobic glycolysis, which further antagonizes outcomes by localized increases in lactate, an immune suppressor. Recent evidence indicates that enzymatic lowering of lactate can promote an oncolytic immune microenvironment within the tumour. Here, we review factors relating to lactate expression in NSCLC and the utility of lactate oxidase (LOX) for governing therapeutic delivery, its role in lactate oxidation and turnover, and relationships between lactate depletion and immune cell populations. The lactate-rich characteristic of NSCLC provides an exploitable property to potentially improve NSCLC outcomes and design new therapeutic strategies to integrate with conventional therapies.</description><subject>Anaplastic Lymphoma Kinase - genetics</subject><subject>Animals</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Citric Acid Cycle</subject><subject>Drug Resistance, Neoplasm</subject><subject>Genes, erbB-1 - genetics</subject><subject>Glucose - metabolism</subject><subject>Humans</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>L-Lactate Dehydrogenase - antagonists & inhibitors</subject><subject>Lactate</subject><subject>Lactate oxidase</subject><subject>Lactic Acid - metabolism</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Metabolic Networks and Pathways</subject><subject>Mixed Function Oxygenases - therapeutic use</subject><subject>Molecular Targeted Therapy</subject><subject>Nanoparticles</subject><subject>Nonsmall cell lung cancer</subject><subject>NSCLC</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>Tumor Microenvironment</subject><issn>1359-6446</issn><issn>1878-5832</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EoqXwBwhlySbBj9hONkio4iVVogtYW449AVd5FNtB4u9x1cKSzXgWZ-aOD0KXBBcEE3GzKayfrAsFxZQUWBaYlEdoTipZ5bxi9Dj1jNe5KEsxQ2chbDAmtObiFM1YySjHBM_Rej1GGKLTXRY_wOstTNGZkE3BDe9ZnPrR5wGMhwg267SJOkLmhmwYh9DrrssMpNJNCTZ6MODP0UmruwAXh3eB3h7uX5dP-erl8Xl5t8oNEzTmKb22mktGqkZqaHUjSs0aKkVlmRDWippRKY2uSVtzxq0sK-DEWtlIsOn-Bbre79368XOCEFXvwu4YPcA4BUU5lzRtr-qElnvU-DEED63aetdr_60IVjuXaqP2LtXOpcJSJZdp7OqQMDU92L-hX3kJuN0DkP755cCrYBwkCdZ5MFHZ0f2f8AMfpYfN</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Liao, Zi-Xian</creator><creator>Kempson, Ivan M.</creator><creator>Hsieh, Chia-Chen</creator><creator>Tseng, S.-Ja</creator><creator>Yang, Pan-Chyr</creator><general>Elsevier Ltd</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>7X8</scope><orcidid>https://orcid.org/0000-0001-6521-7620</orcidid><orcidid>https://orcid.org/0000-0002-1299-7202</orcidid></search><sort><creationdate>202111</creationdate><title>Potential therapeutics using tumor-secreted lactate in nonsmall cell lung cancer</title><author>Liao, Zi-Xian ; Kempson, Ivan M. ; Hsieh, Chia-Chen ; Tseng, S.-Ja ; Yang, Pan-Chyr</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-5019da57318b7aefab64a3b2768d366dd693277ca91f9535d748e51dd7b7ed343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anaplastic Lymphoma Kinase - genetics</topic><topic>Animals</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Citric Acid Cycle</topic><topic>Drug Resistance, Neoplasm</topic><topic>Genes, erbB-1 - genetics</topic><topic>Glucose - metabolism</topic><topic>Humans</topic><topic>Immune Checkpoint Inhibitors - therapeutic use</topic><topic>L-Lactate Dehydrogenase - antagonists & inhibitors</topic><topic>Lactate</topic><topic>Lactate oxidase</topic><topic>Lactic Acid - metabolism</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Metabolic Networks and Pathways</topic><topic>Mixed Function Oxygenases - therapeutic use</topic><topic>Molecular Targeted Therapy</topic><topic>Nanoparticles</topic><topic>Nonsmall cell lung cancer</topic><topic>NSCLC</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>Tumor Microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liao, Zi-Xian</creatorcontrib><creatorcontrib>Kempson, Ivan M.</creatorcontrib><creatorcontrib>Hsieh, Chia-Chen</creatorcontrib><creatorcontrib>Tseng, S.-Ja</creatorcontrib><creatorcontrib>Yang, Pan-Chyr</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Drug discovery today</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liao, Zi-Xian</au><au>Kempson, Ivan M.</au><au>Hsieh, Chia-Chen</au><au>Tseng, S.-Ja</au><au>Yang, Pan-Chyr</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potential therapeutics using tumor-secreted lactate in nonsmall cell lung cancer</atitle><jtitle>Drug discovery today</jtitle><addtitle>Drug Discov Today</addtitle><date>2021-11</date><risdate>2021</risdate><volume>26</volume><issue>11</issue><spage>2508</spage><epage>2514</epage><pages>2508-2514</pages><issn>1359-6446</issn><eissn>1878-5832</eissn><abstract>•Non-small cell lung cancer (NSCLC) frequently presents genetic mutuations.•NSCLC upregulates glucose metabolism and subsequent accumulates lactate.•Lactate as key molecule leads various phenomena in tumor microenvironment.•Lactate oxidase (LOX) can directly oxidize tumor-secreted lactate.•Consuming or oxidizing tumor-secreted lactate provides a potential route.
Targeted-therapy failure in treating nonsmall cell lung cancer (NSCLC) frequently occurs because of the emergence of drug resistance and genetic mutations. The same mutations also result in aerobic glycolysis, which further antagonizes outcomes by localized increases in lactate, an immune suppressor. Recent evidence indicates that enzymatic lowering of lactate can promote an oncolytic immune microenvironment within the tumour. Here, we review factors relating to lactate expression in NSCLC and the utility of lactate oxidase (LOX) for governing therapeutic delivery, its role in lactate oxidation and turnover, and relationships between lactate depletion and immune cell populations. The lactate-rich characteristic of NSCLC provides an exploitable property to potentially improve NSCLC outcomes and design new therapeutic strategies to integrate with conventional therapies.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34325010</pmid><doi>10.1016/j.drudis.2021.07.014</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-6521-7620</orcidid><orcidid>https://orcid.org/0000-0002-1299-7202</orcidid></addata></record> |
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| subjects | Anaplastic Lymphoma Kinase - genetics Animals Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Citric Acid Cycle Drug Resistance, Neoplasm Genes, erbB-1 - genetics Glucose - metabolism Humans Immune Checkpoint Inhibitors - therapeutic use L-Lactate Dehydrogenase - antagonists & inhibitors Lactate Lactate oxidase Lactic Acid - metabolism Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - metabolism Metabolic Networks and Pathways Mixed Function Oxygenases - therapeutic use Molecular Targeted Therapy Nanoparticles Nonsmall cell lung cancer NSCLC Protein Kinase Inhibitors - therapeutic use Proto-Oncogene Proteins p21(ras) - genetics Tumor Microenvironment |
| title | Potential therapeutics using tumor-secreted lactate in nonsmall cell lung cancer |
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