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<p>Defects in the DNA damage response (DDR) can cause genomic instability, leading to genetic mutations or abnormalities that promote cancer growth and progression. Gastrointestinal (GI) cancers are lagging behind other types of tumors in terms of customized therapy with targeted drugs. PARP inhibitors (PARPi) were the first approved cancer treatments to target the DNA damage response in BRCA1/2-mutated breast and ovarian malignancies. Since then, our understanding of the processes underlying tumor sensitization to PARP inhibitors has advanced significantly, as has the use of PARP inhibitors to treat various additional cancer types. Existing methods for assessing the sensitivity of gastrointestinal malignancies to PARP inhibitors rely on extrapolations from other cancer types, regardless of the inconsistency in defining homologous recombination (HR) status across tumor types. Due to the pressing clinical demand, it is critical to have a better knowledge of the therapeutic consequences of DDR alterations in gastrointestinal cancers. Today, combination therapy is used as an effective treatment method in the treatment of cancers. This article attempts to summarize and present the latest findings on the combination therapy of gastrointestinal cancers using PARP inhibitors and other products, especially immunotherapy ones.</p>

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A comprehensive review of immunotherapy in gastrointestinal tumors with a focus on the role of combination therapy with PARP inhibitors

  • 期刊论文

  • 发表日期：

    2025年6月9日

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  • Saade Abdalkareem Jasim,
  • Jitendra Gupta,
  • Subasini Uthirapathy,
  • Roopashree R.,
  • Syeda Wajida Kazmi,
  • Jasur Alimdjanovich Rizaev,
  • Mamdouh Eldesoqui,
  • Maythum Ali Shallan,
  • Yasser Fakri Mustafa,
  • Beneen Hosseen

摘要

Defects in the DNA damage response (DDR) can cause genomic instability, leading to genetic mutations or abnormalities that promote cancer growth and progression. Gastrointestinal (GI) cancers are lagging behind other types of tumors in terms of customized therapy with targeted drugs. PARP inhibitors (PARPi) were the first approved cancer treatments to target the DNA damage response in BRCA1/2-mutated breast and ovarian malignancies. Since then, our understanding of the processes underlying tumor sensitization to PARP inhibitors has advanced significantly, as has the use of PARP inhibitors to treat various additional cancer types. Existing methods for assessing the sensitivity of gastrointestinal malignancies to PARP inhibitors rely on extrapolations from other cancer types, regardless of the inconsistency in defining homologous recombination (HR) status across tumor types. Due to the pressing clinical demand, it is critical to have a better knowledge of the therapeutic consequences of DDR alterations in gastrointestinal cancers. Today, combination therapy is used as an effective treatment method in the treatment of cancers. This article attempts to summarize and present the latest findings on the combination therapy of gastrointestinal cancers using PARP inhibitors and other products, especially immunotherapy ones.