Frontiers in Anti-Cancer Drug Discovery

Volume: 9

Recent Advances and New Insights for the Therapeutic Intervention of Cancer

Author(s): Nhi Nguyen, Stina George Fernandes, Ekta Khattar and Yinghui Li

Pp: 1-63 (63)

DOI: 10.2174/9781681087016118090003

* (Excluding Mailing and Handling)

Abstract

Traditionally, anti-cancer treatments mainly focus on chemotherapies, radiation therapy and surgery. However, these treatments are limited in terms of their specificity for targeting only cancer cells. DNA damaging chemotherapy is one of the most common treatment modalities of cancer. Current progress of targeted therapy that relies on DNA damage response (DDR) in cancer offers a vast therapeutic window by specifically targeting DDR functions in patient specific tumours. Recent developments in immunotherapy – therapy that boosts the body’s immune system to fight against cancer cells, have shown promising results. Currently, different approaches of immunotherapies such as cytokine, antibody, oncolytic virus, adoptive cell transfer therapies or cancer vaccination have made significant progress in treating different cancer types. This paper seeks to provide an overview of the recent developments of drugs targeting DDR and various immunotherapeutic approaches, with specific focus on the anti-CD19 CAR-T cell therapy. Finally, the paper will give a perspective on future directions of DDR therapy, CAR-T cell therapy as well as the combination of different cancer therapies for effective cancer treatment regime.

Over the past few years, the decipher of different DNA damage response mechanisms enables the development of novel inhibitors for cancer treatment. Furthermore, recent advances in genomic editing technologies and scientific discoveries reveal important roles of the immune system in the context of cancer development. This also prompts the plethora of drug developments that have vast potential in the treatment of different types of cancer diseases. This paper will give an overview of recent drug developments in chemotherapeutic agents targeting DNA damage response as well as recent immunotherapies that have been successful in the treatment of human cancers. The contents discussed in the paper are summarized in (Fig. 1).


Keywords: Adoptive Cell Transfer Therapies, Antibody Therapy, Anti-CD19 CAR-T Cell Therapy, Combinational Approaches, Cytokine Therapy, DNA Damage Response, DNA Damage Response Inhibitors, Immunotherapy, Oncolytic Virus Approach.

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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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1740515473 and j.to_date >= 1740515473 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12782) 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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1740515473 and j.to_date >= 1740515473 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12782) 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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1740515473 and j.to_date >= 1740515473 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12782)
      590μsalphaeurekaselec_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` = 2632 and `b`.`banner_from_date` <= 1740515473 and `b`.`banner_to_date` >= 1740515473 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.1msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2632
      • 3: 1740515473
      • 4: 1740515473
      • 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='a153abf8fcba2a68cd13179002f69d8e'
      260μsalphaeurekaselec_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
    9Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        r1APdkFLDxMn7C8PkV9BaGtl9jMuFWazA6ZwVoDg
        uc_cart_id
        a153abf8fcba2a68cd13179002f69d8e
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12782" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/12782
        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=eyJpdiI6InFaMXFwUWFLMFNrN1N3VzE5SG05elE9PSIsInZhbHVlIjoiUTY3VnFxWEhWMmpTRENLUXpkVTNIdVBvWEZtSE9wOWd0eGpZRSt4cUNKbz0iLCJtYWMiOiIwYWQwZjY0NzJiN2IxYTY4MzVmYmQ5ZDU5MGMzNWNlZTk1ODE3YzM4ZjA4M2ZkZjU1NDAxMGE2YzVkNzhlNTA0IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InFaMXFwUWFLMFNrN1N3VzE5SG05elE9PSIsInZhbHVlIjoiUTY3VnFxWEhWMmpTRENLUXpkVTNIdVBvWEZtSE9wOWd0eGpZRSt4cUNKbz0iLCJtYWMiOiIwYWQwZjY0NzJiN2Ix" ] "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 20:31:13 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Ikc0aTRoMjliaVp3R2NLL2I5VTVRdXc9PSIsInZhbHVlIjoiYnQrTkFQMDl0QWdMdzlac0xMS2VoaVd3NkZ0MkdMRjVUaEZqTDNibXJ5cmQ2UkJXeGFqMG1kVHpOK2R6VHJKR00wWGdPOVh2U2huWVBOTGNZMk9DdUlnMEYyaGM4QUNKVlBSSG9PdUxkNkFnRmhmVlplRVg5UHYvVzlzZVFSQmQiLCJtYWMiOiIxZmE2ZmQzZThhYzdjNWM0MTM3NWJjMjNiOTE3ZTkxOWNiZGM0YTAzN2U1ZGM2NDFiY2VhZWI3ZmFmMjY1YjQyIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 08:31:13 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6Ikc0aTRoMjliaVp3R2NLL2I5VTVRdXc9PSIsInZhbHVlIjoiYnQrTkFQMDl0QWdMdzlac0xMS2VoaVd3NkZ0MkdMRjVUaEZqTDNibXJ5cmQ2UkJXeGFqMG1kVHpOK2R6VHJKR00wWGdPO" 1 => "alphaeurekaselectnet_session=eyJpdiI6IitGdG5CUkVIdDJjUTV1alpSaWI3dVE9PSIsInZhbHVlIjoiNGcvNlJDUmhJLy83K0xucWkraCszajJnWFB3dG9GNGVhL1hURUM1elVVTHg2MjV5NHEvVncveDhzZHFSZEJRVzJoMFh6RUpKNXlHK1FUdEt1V1ZXOEZVVkFkVi9acGhWdWJsOW9Ha2p0Zks0bmxBWEQ5d3BJbTIvRkdZVWJqK28iLCJtYWMiOiIxNmE5NmI1N2IxNGEzNjFhMjhlNTUxYzAyNjU5MWFhMDk3NDZkMTUxZjdkZDQ5NmUzYjlkMDM5ZDI4NTY4NzJjIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IitGdG5CUkVIdDJjUTV1alpSaWI3dVE9PSIsInZhbHVlIjoiNGcvNlJDUmhJLy83K0xucWkraCszajJnWFB3dG9GNGVhL1hURUM1elVVTHg2MjV5NHEvVncveDh" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Ikc0aTRoMjliaVp3R2NLL2I5VTVRdXc9PSIsInZhbHVlIjoiYnQrTkFQMDl0QWdMdzlac0xMS2VoaVd3NkZ0MkdMRjVUaEZqTDNibXJ5cmQ2UkJXeGFqMG1kVHpOK2R6VHJKR00wWGdPOVh2U2huWVBOTGNZMk9DdUlnMEYyaGM4QUNKVlBSSG9PdUxkNkFnRmhmVlplRVg5UHYvVzlzZVFSQmQiLCJtYWMiOiIxZmE2ZmQzZThhYzdjNWM0MTM3NWJjMjNiOTE3ZTkxOWNiZGM0YTAzN2U1ZGM2NDFiY2VhZWI3ZmFmMjY1YjQyIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 08:31:13 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6Ikc0aTRoMjliaVp3R2NLL2I5VTVRdXc9PSIsInZhbHVlIjoiYnQrTkFQMDl0QWdMdzlac0xMS2VoaVd3NkZ0MkdMRjVUaEZqTDNibXJ5cmQ2UkJXeGFqMG1kVHpOK2R6VHJKR00wWGdPO" 1 => "alphaeurekaselectnet_session=eyJpdiI6IitGdG5CUkVIdDJjUTV1alpSaWI3dVE9PSIsInZhbHVlIjoiNGcvNlJDUmhJLy83K0xucWkraCszajJnWFB3dG9GNGVhL1hURUM1elVVTHg2MjV5NHEvVncveDhzZHFSZEJRVzJoMFh6RUpKNXlHK1FUdEt1V1ZXOEZVVkFkVi9acGhWdWJsOW9Ha2p0Zks0bmxBWEQ5d3BJbTIvRkdZVWJqK28iLCJtYWMiOiIxNmE5NmI1N2IxNGEzNjFhMjhlNTUxYzAyNjU5MWFhMDk3NDZkMTUxZjdkZDQ5NmUzYjlkMDM5ZDI4NTY4NzJjIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IitGdG5CUkVIdDJjUTV1alpSaWI3dVE9PSIsInZhbHVlIjoiNGcvNlJDUmhJLy83K0xucWkraCszajJnWFB3dG9GNGVhL1hURUM1elVVTHg2MjV5NHEvVncveDh" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "r1APdkFLDxMn7C8PkV9BaGtl9jMuFWazA6ZwVoDg" "uc_cart_id" => "a153abf8fcba2a68cd13179002f69d8e" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12782" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 20:31:13GET/chapter/127821121911