Frontiers in Anti-Cancer Drug Discovery

Volume: 6

Frontiers in Biological Therapies for Advanced Hepatocellular Carcinoma

Author(s): Liat Mlynarsky, Liane Rabinowich, Brian I. Carr and Oren Shibolet

Pp: 196-217 (22)

DOI: 10.2174/9781681081496115060008

* (Excluding Mailing and Handling)

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third commonest cause of tumor associated death worldwide. The incidence of HCC is increasing worldwide in both developing and developed countries. There are three potentially curative treatments for HCC: resection, liver transplantation and radiofrequency ablation. However, these are only suitable for patients meeting strict pre-defined criteria with compensated liver disease and small tumors. Patients who are not suitable for these therapies can be treated by loco-ablative or systemic therapies. Sorafenib, is the first and only systemic therapy that has been approved by regulatory agencies and demonstrated a survival benefit for patients with advanced HCC. In this chapter we review current therapy choices and focus on pipeline therapeutic options for advanced HCC, especially biological therapies.


Keywords: Biological therapies, chemoembolization, hepatocellular carcinoma, liver transplantation, loco-ablative therapies, radiofrequency ablation, resection, Sorafenib.

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      450μsalphaeurekaselec_live_10_06_2022Subject.php#255
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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
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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 <= 59071449 and j.to_ip >=59071449 )) and ((j.from_date <= 1740497291 and j.to_date >= 1740497291 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 8225) 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 <= 59071449 and j.to_ip >=59071449 )) and ((j.from_date <= 1740497291 and j.to_date >= 1740497291 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 8225) 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 <= 59071449 and j.to_ip >=59071449 )) and ((j.from_date <= 1740497291 and j.to_date >= 1740497291 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 8225)
      600μsalphaeurekaselec_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` = 1885 and `b`.`banner_from_date` <= 1740497291 and `b`.`banner_to_date` >= 1740497291 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.09msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1885
      • 3: 1740497291
      • 4: 1740497291
      • 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='7d317e7c63a2393f4b89b3b5dc2ec681'
      240μsalphaeurekaselec_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
        SuY6SzZglG7N9xApZEgO8Ci74UXdFzNlpOFgzdIB
        uc_cart_id
        7d317e7c63a2393f4b89b3b5dc2ec681
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/8225" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/8225
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Iml6ZWkvSzBFdUh1VXVZUU1YWmpHRGc9PSIsInZhbHVlIjoiZ0Fjem05UDVDT1BzOHdzaEN0TWdkdXhPYklEOTRUdnpWOEFjTmo3R1dlST0iLCJtYWMiOiI3MWE5MWQwMjJmYjYxZjA0YWZjYjFlMTdmN2RmNzUxYTZmNjIzN2FhY2VkN2NmNGY3ODZlYTBhNzFlOTA1MzFlIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Iml6ZWkvSzBFdUh1VXVZUU1YWmpHRGc9PSIsInZhbHVlIjoiZ0Fjem05UDVDT1BzOHdzaEN0TWdkdXhPYklEOTRUdnpWOEFjTmo3R1dlST0iLCJtYWMiOiI3MWE5MWQwMjJmYjYx" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        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 => "Tue, 25 Feb 2025 15:28:11 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlY1b3R0MEJTVWVlc2tMMEZBSjFNMGc9PSIsInZhbHVlIjoiMWZnQTJZSldJVUNuRTloTkpKQXlOdGwwRXRFMSt1VHB1ajJ1cjRldTJUc0QvM0JDTFhJd1pFL2tPMWpTRFcyaHhhUmdwdGZXWXU4cWpCMkNyWFpuc2xBWW4wS1g5MndmMkdCRnRaaEZ2dWZhQ0RLZlIwbVN3aW5sRFN1V044NmQiLCJtYWMiOiJiOWYyMTEwNDUxM2FkZmU5YzZhZTZhYjBhMWE4YTkyOTNmNDc5ODkyNmNjNDgzOGMxZjg3ODAxMTFjYjQ3Njk1IiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 03:28:11 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IlY1b3R0MEJTVWVlc2tMMEZBSjFNMGc9PSIsInZhbHVlIjoiMWZnQTJZSldJVUNuRTloTkpKQXlOdGwwRXRFMSt1VHB1ajJ1cjRldTJUc0QvM0JDTFhJd1pFL2tPMWpTRFcyaHhhUmdwd" 1 => "alphaeurekaselectnet_session=eyJpdiI6Im5NN3U3VTRLT0llNVN1R3dhaGE3cHc9PSIsInZhbHVlIjoiR0MvOTBGY3JNMytneTZnd3o4Y0ZTR1I5Qm9xMDRsK2lMQjVjeVRrQnAybWhvZ1FRMG51aGJ4STMrT0RlSUcrZ01NQkJTNFFxUWROaTJJeitCUzh0bVdVaHZhNmNWaU5BMHlHVHRwc2x2aVBZSjBITUJUK21xRHFEZUJOdHh2RnIiLCJtYWMiOiI3MTM3MjE3ZDU2MGViZWMwMzMxY2IwMzc1YWU1MDA4Yzc4MTliZjIxMGJkNGYzNGEwNDBkMzI2OGE1MDI3N2QzIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Im5NN3U3VTRLT0llNVN1R3dhaGE3cHc9PSIsInZhbHVlIjoiR0MvOTBGY3JNMytneTZnd3o4Y0ZTR1I5Qm9xMDRsK2lMQjVjeVRrQnAybWhvZ1FRMG51aGJ4STM" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlY1b3R0MEJTVWVlc2tMMEZBSjFNMGc9PSIsInZhbHVlIjoiMWZnQTJZSldJVUNuRTloTkpKQXlOdGwwRXRFMSt1VHB1ajJ1cjRldTJUc0QvM0JDTFhJd1pFL2tPMWpTRFcyaHhhUmdwdGZXWXU4cWpCMkNyWFpuc2xBWW4wS1g5MndmMkdCRnRaaEZ2dWZhQ0RLZlIwbVN3aW5sRFN1V044NmQiLCJtYWMiOiJiOWYyMTEwNDUxM2FkZmU5YzZhZTZhYjBhMWE4YTkyOTNmNDc5ODkyNmNjNDgzOGMxZjg3ODAxMTFjYjQ3Njk1IiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 03:28:11 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IlY1b3R0MEJTVWVlc2tMMEZBSjFNMGc9PSIsInZhbHVlIjoiMWZnQTJZSldJVUNuRTloTkpKQXlOdGwwRXRFMSt1VHB1ajJ1cjRldTJUc0QvM0JDTFhJd1pFL2tPMWpTRFcyaHhhUmdwd" 1 => "alphaeurekaselectnet_session=eyJpdiI6Im5NN3U3VTRLT0llNVN1R3dhaGE3cHc9PSIsInZhbHVlIjoiR0MvOTBGY3JNMytneTZnd3o4Y0ZTR1I5Qm9xMDRsK2lMQjVjeVRrQnAybWhvZ1FRMG51aGJ4STMrT0RlSUcrZ01NQkJTNFFxUWROaTJJeitCUzh0bVdVaHZhNmNWaU5BMHlHVHRwc2x2aVBZSjBITUJUK21xRHFEZUJOdHh2RnIiLCJtYWMiOiI3MTM3MjE3ZDU2MGViZWMwMzMxY2IwMzc1YWU1MDA4Yzc4MTliZjIxMGJkNGYzNGEwNDBkMzI2OGE1MDI3N2QzIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Im5NN3U3VTRLT0llNVN1R3dhaGE3cHc9PSIsInZhbHVlIjoiR0MvOTBGY3JNMytneTZnd3o4Y0ZTR1I5Qm9xMDRsK2lMQjVjeVRrQnAybWhvZ1FRMG51aGJ4STM" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "SuY6SzZglG7N9xApZEgO8Ci74UXdFzNlpOFgzdIB" "uc_cart_id" => "7d317e7c63a2393f4b89b3b5dc2ec681" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/8225" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 15:28:11GET/chapter/82251121910