Frontiers in Anti-Cancer Drug Discovery

Volume: 1

Aurora Kinase Family: A New Target for Anticancer Drug

Author(s): '> Teresa Macarulla, M. Elena Elez, Francisco Javier Ramos, Josep Tabernero

Pp: 132-148 (17)

DOI: 10.2174/978160805161811001010132

* (Excluding Mailing and Handling)

Abstract

Aurora kinases (AK) are the name given to a family of Serine/threonine (Ser/Thr) protein kinases. These proteins represent a novel family of kinases crucial for cell cycle control. The cell division process is one of the hallmarks of every living organism. Within the complete cell-cycle process, mitosis constitutes one of the most critical steps. The main purpose of mitosis is to segregate sister chromatics into two daughters cells. It is a complex biologic process, and errors in this mechanism can lead to genomic instability, a condition associated with tumorigenesis. This process is tightly regulated by several proteins, some of them acting as check-points that ultimately ensure the correct temporal and spatial coordination of this critical biologic process. Among this network of mitotic regulators, AK play a critical role in cellular division by controlling chromatid segregation. Three AK family members have been identified in mammalian cells: A, B, and C. These proteins are implicated in several vital events in mitosis. In experimental models, overexpression of AK can induce spindle defects, chromosome mis-segregation, and malignant transformation. Conversely, downregulation of AK expression causes mitotic arrest and apoptosis in tumor cell lines. The expression levels of human AK are increased in certain types of cancer including breast, colon, pancreatic, ovarian, and gastric tumors. This observation has lent an interest to this family of kinases as potential drug targets for development of new anticancer therapies. This review focuses in recent progress in the role of AK in tumorogenesis and the development of new anticancer drug against AK proteins. This manuscript includes some relevant patents as well.


Keywords: Aurora kinases, mitosis, checkpoint, anticancer drug

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      • 11. app/Models/ContentAccess.php:647
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      • 13. app/Models/UserAccess/UserAccess.php:1266
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      • 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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1739834833 and j.to_date >= 1739834833 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1766) 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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1739834833 and j.to_date >= 1739834833 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1766) 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 <= 221922387 and j.to_ip >=221922387 )) and ((j.from_date <= 1739834833 and j.to_date >= 1739834833 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1766)
      560μsalphaeurekaselec_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` = 919 and `b`.`banner_from_date` <= 1739834833 and `b`.`banner_to_date` >= 1739834833 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.03msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 919
      • 3: 1739834833
      • 4: 1739834833
      • 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='5bfb706096ef0901ecd3bf42450035dd'
      200μsalphaeurekaselec_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
    4Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        GYMrw7iW4P6STYkz881Rwkvwtp7Oxbt8y0LLwR0H
        uc_cart_id
        5bfb706096ef0901ecd3bf42450035dd
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1766" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
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        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
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Mon, 17 Feb 2025 23:27:13 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkhJT1pXMVBCcUhpZzhUWEpXZFFHcFE9PSIsInZhbHVlIjoiVkxrQXhlbWgrYktJY3JBQytkNUVCOGUxNU5XS0xGalJqOXY2MkZnUitWVU9vZXllREtBemk1S1o4WU9OSEtKVkpBYjhJeUJoUmN2VnR5Wmd2OHBqNi9GeXh5d2hsb0tuOXpPbWxkd1NXM2JOdVU5MHZYR0JXd1dZVUZoOWpOYTMiLCJtYWMiOiI4Yjc5N2RiMWQ1ODQ2NWI1YWI1ZmE5MDEzMmJhZmEyNjJkOGQwMTg1NzljMjQ0YmU2MmE5Zjg2MDdhMDU0ZWJkIiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 11:27:13 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkhJT1pXMVBCcUhpZzhUWEpXZFFHcFE9PSIsInZhbHVlIjoiVkxrQXhlbWgrYktJY3JBQytkNUVCOGUxNU5XS0xGalJqOXY2MkZnUitWVU9vZXllREtBemk1S1o4WU9OSEtKVkpBYjhJe" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ik8xQmNQR0YwNDVBTXZ2YTBGc1l3bkE9PSIsInZhbHVlIjoieUIwYXU3MnNkd21kYlRGMXFBajNGYmtIYWtlTlIzSUVPMnpGTTNRUnpzMHhabWV2RDlBS0s0ZG1QV3F5WkhYNG5HWHYzaVNKR3VyZnZFdVV1NEJGUDZtTDVxSXZ5ZHVMRUtac293dGJSZXdYWENuZ2hvck5VcjRnWjRiZzFobFAiLCJtYWMiOiJmODZkOTcxYzBmYTQ2ODhhNzhkMjA5NWVhNDdiZGJiNGUwMTkyNzcyNGU2ZjEyZjg4NDA0MzZmYjQ1ZDg3NjJhIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Ik8xQmNQR0YwNDVBTXZ2YTBGc1l3bkE9PSIsInZhbHVlIjoieUIwYXU3MnNkd21kYlRGMXFBajNGYmtIYWtlTlIzSUVPMnpGTTNRUnpzMHhabWV2RDlBS0s0ZG1" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkhJT1pXMVBCcUhpZzhUWEpXZFFHcFE9PSIsInZhbHVlIjoiVkxrQXhlbWgrYktJY3JBQytkNUVCOGUxNU5XS0xGalJqOXY2MkZnUitWVU9vZXllREtBemk1S1o4WU9OSEtKVkpBYjhJeUJoUmN2VnR5Wmd2OHBqNi9GeXh5d2hsb0tuOXpPbWxkd1NXM2JOdVU5MHZYR0JXd1dZVUZoOWpOYTMiLCJtYWMiOiI4Yjc5N2RiMWQ1ODQ2NWI1YWI1ZmE5MDEzMmJhZmEyNjJkOGQwMTg1NzljMjQ0YmU2MmE5Zjg2MDdhMDU0ZWJkIiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 11:27:13 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkhJT1pXMVBCcUhpZzhUWEpXZFFHcFE9PSIsInZhbHVlIjoiVkxrQXhlbWgrYktJY3JBQytkNUVCOGUxNU5XS0xGalJqOXY2MkZnUitWVU9vZXllREtBemk1S1o4WU9OSEtKVkpBYjhJe" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ik8xQmNQR0YwNDVBTXZ2YTBGc1l3bkE9PSIsInZhbHVlIjoieUIwYXU3MnNkd21kYlRGMXFBajNGYmtIYWtlTlIzSUVPMnpGTTNRUnpzMHhabWV2RDlBS0s0ZG1QV3F5WkhYNG5HWHYzaVNKR3VyZnZFdVV1NEJGUDZtTDVxSXZ5ZHVMRUtac293dGJSZXdYWENuZ2hvck5VcjRnWjRiZzFobFAiLCJtYWMiOiJmODZkOTcxYzBmYTQ2ODhhNzhkMjA5NWVhNDdiZGJiNGUwMTkyNzcyNGU2ZjEyZjg4NDA0MzZmYjQ1ZDg3NjJhIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Ik8xQmNQR0YwNDVBTXZ2YTBGc1l3bkE9PSIsInZhbHVlIjoieUIwYXU3MnNkd21kYlRGMXFBajNGYmtIYWtlTlIzSUVPMnpGTTNRUnpzMHhabWV2RDlBS0s0ZG1" ] ]
        session_attributes
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        array:5 [ "_token" => "GYMrw7iW4P6STYkz881Rwkvwtp7Oxbt8y0LLwR0H" "uc_cart_id" => "5bfb706096ef0901ecd3bf42450035dd" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1766" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:27:13GET/chapter/1766112196