In search of effective therapies to overcome resistance to Temozolomide in brain tumours
Glioblastoma multiforme is the most common and lethal brain tumour-type. The current standard of care includes Temozolomide (TMZ) chemotherapy. However, inherent and acquired resistance to TMZ thwart successful treatment. The direct repair protein methylguanine DNA methyltransferase (MGMT) removes t...
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| Veröffentlicht in: | Cancer Drug Resistance 2019-01, Vol.2 (4), p.1018-1031 |
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| creator | Bouzinab, Kaouthar Summers, Helen Zhang, Jihong Stevens, Malcolm F G Moody, Christopher J Turyanska, Lyudmila Thomas, Neil R Gershkovich, Pavel Ashford, Marianne B Vitterso, Emily Storer, Lisa C D Grundy, Richard Bradshaw, Tracey D |
| description | Glioblastoma multiforme is the most common and lethal brain tumour-type. The current standard of care includes Temozolomide (TMZ) chemotherapy. However, inherent and acquired resistance to TMZ thwart successful treatment. The direct repair protein methylguanine DNA methyltransferase (MGMT) removes the cytotoxic
-methylguanine (
6-MeG) lesion delivered by TMZ and so its expression by tumours confers TMZ-resistance. DNA mismatch repair (MMR) is essential to process
6-MeG adducts and MMR-deficiency leads to tolerance of lesions, resistance to TMZ and further DNA mutations. In this article, two strategies to overcome TMZ resistance are discussed: (1) synthesis of imidazotetrazine analogues - designed to retain activity in the presence of MGMT or loss of MMR; (2) preparation of imidazotetrazine-nanoparticles to deliver TMZ preferably to the brain and tumour site. Our promising results encourage belief in a future where better prognoses exist for patients diagnosed with this devastating disease. |
| doi_str_mv | 10.20517/cdr.2019.64 |
| format | Article |
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-methylguanine (
6-MeG) lesion delivered by TMZ and so its expression by tumours confers TMZ-resistance. DNA mismatch repair (MMR) is essential to process
6-MeG adducts and MMR-deficiency leads to tolerance of lesions, resistance to TMZ and further DNA mutations. In this article, two strategies to overcome TMZ resistance are discussed: (1) synthesis of imidazotetrazine analogues - designed to retain activity in the presence of MGMT or loss of MMR; (2) preparation of imidazotetrazine-nanoparticles to deliver TMZ preferably to the brain and tumour site. Our promising results encourage belief in a future where better prognoses exist for patients diagnosed with this devastating disease.</description><identifier>EISSN: 2578-532X</identifier><identifier>DOI: 10.20517/cdr.2019.64</identifier><identifier>PMID: 35582280</identifier><language>eng</language><publisher>United States: OAE Publishing Inc</publisher><subject>Review</subject><ispartof>Cancer Drug Resistance, 2019-01, Vol.2 (4), p.1018-1031</ispartof><rights>The Author(s) 2019.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-b89a183b2e43f1749633964ce1cf62742c0033ea7db252d122e51cb7309a84da3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019207/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019207/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35582280$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bouzinab, Kaouthar</creatorcontrib><creatorcontrib>Summers, Helen</creatorcontrib><creatorcontrib>Zhang, Jihong</creatorcontrib><creatorcontrib>Stevens, Malcolm F G</creatorcontrib><creatorcontrib>Moody, Christopher J</creatorcontrib><creatorcontrib>Turyanska, Lyudmila</creatorcontrib><creatorcontrib>Thomas, Neil R</creatorcontrib><creatorcontrib>Gershkovich, Pavel</creatorcontrib><creatorcontrib>Ashford, Marianne B</creatorcontrib><creatorcontrib>Vitterso, Emily</creatorcontrib><creatorcontrib>Storer, Lisa C D</creatorcontrib><creatorcontrib>Grundy, Richard</creatorcontrib><creatorcontrib>Bradshaw, Tracey D</creatorcontrib><title>In search of effective therapies to overcome resistance to Temozolomide in brain tumours</title><title>Cancer Drug Resistance</title><addtitle>Cancer Drug Resist</addtitle><description>Glioblastoma multiforme is the most common and lethal brain tumour-type. The current standard of care includes Temozolomide (TMZ) chemotherapy. However, inherent and acquired resistance to TMZ thwart successful treatment. The direct repair protein methylguanine DNA methyltransferase (MGMT) removes the cytotoxic
-methylguanine (
6-MeG) lesion delivered by TMZ and so its expression by tumours confers TMZ-resistance. DNA mismatch repair (MMR) is essential to process
6-MeG adducts and MMR-deficiency leads to tolerance of lesions, resistance to TMZ and further DNA mutations. In this article, two strategies to overcome TMZ resistance are discussed: (1) synthesis of imidazotetrazine analogues - designed to retain activity in the presence of MGMT or loss of MMR; (2) preparation of imidazotetrazine-nanoparticles to deliver TMZ preferably to the brain and tumour site. Our promising results encourage belief in a future where better prognoses exist for patients diagnosed with this devastating disease.</description><subject>Review</subject><issn>2578-532X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpVkctLxDAQxoMgKro3z5KjB3dNJq_2Ioj4AsGLwt5Cmk7dSNusSbugf731iV5mhpkf3wzzEXLI2QKY4ubU12mqeLnQcovsgTLFXAlY7pJZzs-MMSgBoFQ7ZFcoVQAUbI8sb3ua0SW_orGh2DToh7BBOqwwuXXATIdI4waTjx3ShDnkwfUeP9oP2MW32MYu1EhDT6vkpjiMXRxTPiDbjWszzr7zPnm8uny4uJnf3V_fXpzfzb0o5DCvitLxQlSAUjTcyFILUWrpkftGg5HgGRMCnakrUFBzAFTcV0aw0hWydmKfnH3prseqw9pjPyTX2nUKnUuvNrpg_0_6sLJPcWPL6VPAzCRw_C2Q4suIebBdyB7b1vUYx2xBa62kMUJP6MkX6lPMOWHzu4Yz--mBnTywHx5YLSf86O9pv_DP98U7FRWFyA</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Bouzinab, Kaouthar</creator><creator>Summers, Helen</creator><creator>Zhang, Jihong</creator><creator>Stevens, Malcolm F G</creator><creator>Moody, Christopher J</creator><creator>Turyanska, Lyudmila</creator><creator>Thomas, Neil R</creator><creator>Gershkovich, Pavel</creator><creator>Ashford, Marianne B</creator><creator>Vitterso, Emily</creator><creator>Storer, Lisa C D</creator><creator>Grundy, Richard</creator><creator>Bradshaw, Tracey D</creator><general>OAE Publishing Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190101</creationdate><title>In search of effective therapies to overcome resistance to Temozolomide in brain tumours</title><author>Bouzinab, Kaouthar ; Summers, Helen ; Zhang, Jihong ; Stevens, Malcolm F G ; Moody, Christopher J ; Turyanska, Lyudmila ; Thomas, Neil R ; Gershkovich, Pavel ; Ashford, Marianne B ; Vitterso, Emily ; Storer, Lisa C D ; Grundy, Richard ; Bradshaw, Tracey D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-b89a183b2e43f1749633964ce1cf62742c0033ea7db252d122e51cb7309a84da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Review</topic><toplevel>online_resources</toplevel><creatorcontrib>Bouzinab, Kaouthar</creatorcontrib><creatorcontrib>Summers, Helen</creatorcontrib><creatorcontrib>Zhang, Jihong</creatorcontrib><creatorcontrib>Stevens, Malcolm F G</creatorcontrib><creatorcontrib>Moody, Christopher J</creatorcontrib><creatorcontrib>Turyanska, Lyudmila</creatorcontrib><creatorcontrib>Thomas, Neil R</creatorcontrib><creatorcontrib>Gershkovich, Pavel</creatorcontrib><creatorcontrib>Ashford, Marianne B</creatorcontrib><creatorcontrib>Vitterso, Emily</creatorcontrib><creatorcontrib>Storer, Lisa C D</creatorcontrib><creatorcontrib>Grundy, Richard</creatorcontrib><creatorcontrib>Bradshaw, Tracey D</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Drug Resistance</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bouzinab, Kaouthar</au><au>Summers, Helen</au><au>Zhang, Jihong</au><au>Stevens, Malcolm F G</au><au>Moody, Christopher J</au><au>Turyanska, Lyudmila</au><au>Thomas, Neil R</au><au>Gershkovich, Pavel</au><au>Ashford, Marianne B</au><au>Vitterso, Emily</au><au>Storer, Lisa C D</au><au>Grundy, Richard</au><au>Bradshaw, Tracey D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In search of effective therapies to overcome resistance to Temozolomide in brain tumours</atitle><jtitle>Cancer Drug Resistance</jtitle><addtitle>Cancer Drug Resist</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>2</volume><issue>4</issue><spage>1018</spage><epage>1031</epage><pages>1018-1031</pages><eissn>2578-532X</eissn><abstract>Glioblastoma multiforme is the most common and lethal brain tumour-type. The current standard of care includes Temozolomide (TMZ) chemotherapy. However, inherent and acquired resistance to TMZ thwart successful treatment. The direct repair protein methylguanine DNA methyltransferase (MGMT) removes the cytotoxic
-methylguanine (
6-MeG) lesion delivered by TMZ and so its expression by tumours confers TMZ-resistance. DNA mismatch repair (MMR) is essential to process
6-MeG adducts and MMR-deficiency leads to tolerance of lesions, resistance to TMZ and further DNA mutations. In this article, two strategies to overcome TMZ resistance are discussed: (1) synthesis of imidazotetrazine analogues - designed to retain activity in the presence of MGMT or loss of MMR; (2) preparation of imidazotetrazine-nanoparticles to deliver TMZ preferably to the brain and tumour site. Our promising results encourage belief in a future where better prognoses exist for patients diagnosed with this devastating disease.</abstract><cop>United States</cop><pub>OAE Publishing Inc</pub><pmid>35582280</pmid><doi>10.20517/cdr.2019.64</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Review |
| title | In search of effective therapies to overcome resistance to Temozolomide in brain tumours |
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