Frontiers in Anti-Cancer Drug Discovery

Volume: 2

Targeting the Molecular Circuitry Underlying Glioblastoma Invasion

Author(s): Sean M. Lawless, Johnny C. Akers, Chun-Lin Chen, Rui Liu, Bob Carter and Clark C. Chen

Pp: 264-281 (18)

DOI: 10.2174/9781608058082113020010

* (Excluding Mailing and Handling)

Abstract

Glioblastoma is the most common form of primary brain tumor. It remains one of the deadliest of human cancers. Despite work by dedicated clinicians and scientists over the past forty years, the median survival of the afflicted patients remains approximately 12-14 months.

A major challenge in the treatment of glioblastoma involves its inherently infiltrative and invasive properties. The tendency for the glioblastoma cells to microscopically extend beyond the region of gross anatomic abnormality renders complete surgical resection impossible. Further, glioblastoma infiltration into regions of the cerebrum where the blood-brain-barrier remains intact increases the probability of therapeutic failure. In these contexts, understanding the molecular mechanisms underlying the invasive nature of glioblastoma cells may afford opportunities for meaningful therapeutic development.

One of the central principles that emerged from the past decades of cancer research is that cancer cells subvert molecular circuitry inherent with the cell of origin. As differing aspects of these circuits are manifested during normal development, it comes as no surprise that the patterns of glioblastoma migration and invasion are highly reminiscent of those observed in astrocytes during development. These highly coordinated processes include establishment of cell polarity, directional cellular adhesion to the extracellular matrix, cytoskeletal rearrangement, and asymmetric detachment to the extracellular matrix. Our understanding of the factors that mediate these cues have led to novel therapeutic strategies.

This chapter will highlight our current understanding of the signaling pathways that mediate glioblastoma chemotaxis with special focus on pharmacologic inhibitors available for therapeutic interventions.


Keywords: Chemotaxis, brain tumor, CD44, cadherin, integrin, metalloproteinases, receptor tyrosine kinase, inhibitors/therapeutics.

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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
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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 <= 59694094 and j.to_ip >=59694094 )) and ((j.from_date <= 1739835109 and j.to_date >= 1739835109 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 5913) 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 <= 59694094 and j.to_ip >=59694094 )) and ((j.from_date <= 1739835109 and j.to_date >= 1739835109 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 5913) 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 <= 59694094 and j.to_ip >=59694094 )) and ((j.from_date <= 1739835109 and j.to_date >= 1739835109 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 5913)
      610μsalphaeurekaselec_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` = 1345 and `b`.`banner_from_date` <= 1739835109 and `b`.`banner_to_date` >= 1739835109 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.08msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1345
      • 3: 1739835109
      • 4: 1739835109
      • 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='0d7bebdcfa6f5e7babaef0a42108c075'
      250μsalphaeurekaselec_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
    8Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        iVc26PEOj8fN7dp0vZV46kFMr5y7dJeACOVNyGGH
        uc_cart_id
        0d7bebdcfa6f5e7babaef0a42108c075
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/5913" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/5913
        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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        session_attributes
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:31:49GET/chapter/59131121910