Advances in Cancer Drug Targets

Volume: 1

Targeting Cancer and Neuropathy with Histone Deacetylase Inhibitors

Author(s): V. Rodriguez-Menendez, L. Tremolizzo and G. Cavaletti

Pp: 238-263 (26)

DOI: 10.2174/9781608054749113010010

* (Excluding Mailing and Handling)

Abstract

Histone deacetylase inhibitors (HDACi) belong to a novel class of drugs able to act on the epigenome, indirectly remodeling the spatial conformation of the chromatin: by increasing histone acetylation these drugs ultimately promote the detachment of DNA from the nucleosome octamer, thereby allowing transcription factors access to the double helix. Such a mechanism of action is of particular interest in the field of cancer treatment, as the reactivation of silenced tumor suppressor genes may be considered as being an important target at which to aim; indeed, it is currently believed that dysregulation of the epigenome plays a major role in cancer. Interestingly, some of the compounds belonging to the HDACi family have additional therapeutic properties, as in the case of valproate that may ameliorate neuropathic pain in animal models and in patients. Conceivably, this is a noteworthy observation, since peripheral neuropathy is a potentially severe side effect of several classes of anticancer agents, such as platinum-derived drugs, antitubulins or protesome inhibitors, limiting effective treatment of the underlying cancer. Based on these data, in this review we will argue that, with respect to other anticancer agents available nowadays, HDACi might offer the advantage not only of targeting the neoplastic disorder, but also of preventing peripheral neuropathies, possibly displaying a complementary mechanism of action.


Keywords: Cisplatin, neuropathy, cancer, histones, valproic acid, neuroprotection.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59584110 and j.to_ip >=59584110 )) and ((j.from_date <= 1739834716 and j.to_date >= 1739834716 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4786) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59584110 and j.to_ip >=59584110 )) and ((j.from_date <= 1739834716 and j.to_date >= 1739834716 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4786) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59584110 and j.to_ip >=59584110 )) and ((j.from_date <= 1739834716 and j.to_date >= 1739834716 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4786)
      900μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1176 and `b`.`banner_from_date` <= 1739834716 and `b`.`banner_to_date` >= 1739834716 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      4.3msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1176
      • 3: 1739834716
      • 4: 1739834716
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='d530e3e46fada69cb12785cc0706a9cf'
      420μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    6Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        O6W2gu9bMB2SudlCh47i926yAjYClRVpfsBX1yek
        uc_cart_id
        d530e3e46fada69cb12785cc0706a9cf
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/4786" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/4786
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        0 of 0
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        response_headers
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:25:16GET/chapter/4786112198