Scholarlink

<p>Acute myeloid leukaemia (AML) remains a challenging haematological malignancy, with most patients developing resistance to standard-of-care (SOC) treatments. This resistance is often attributed to the overexpression of anti-apoptotic BCL-2 family proteins, which regulate the intrinsic apoptotic pathway by inhibiting pro-apoptotic effector proteins such as BAX and BAK. AML cells exploit this imbalance to evade apoptosis and sustain survival, necessitating the development of novel therapeutic strategies. BH3 mimetics are small-molecule inhibitors targeting the pro-survival BCL-2 family proteins and have emerged as promising agents in patients with AML who are unable to receive high-intensity induction chemotherapy. Co-treatment with the BCL-2-specific inhibitor venetoclax and various SOC therapies has been proven effective, with several combinations now approved by the&#xa0;US Food and Drug Administration for adults with AML who are ≥75 years of age and/or are ineligible for intensive induction chemotherapy, on the&#xa0;basis of improved response rates and survival outcomes compared with the previous SOC. In this Review, we highlight the transformative potential of BH3 mimetics in AML therapy, including ongoing studies investigating novel combination regimens and efforts to further refine treatment strategies, with the ultimate goal of improving outcomes for patients with AML.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia

  • 期刊论文

  • 发表日期：

    2025年9月1日

查看全文
  • Antonino Glaviano,
  • Ellen Weisberg,
  • Hiu Y. Lam,
  • Donavan J. J. Tan,
  • Andrew J. Innes,
  • Yubin Ge,
  • Catherine E. Lai,
  • Wendy Stock,
  • Christina Glytsou,
  • Linda Smit,
  • Tatsushi Yoshida,
  • Tian Y. Zhang,
  • Vanessa E. Kennedy,
  • B. Douglas Smith,
  • Thomas Mercher,
  • Stéphane de Botton,
  • Patrizia Diana,
  • Marina Konopleva,
  • Michael J. Mauro,
  • James D. Griffin,
  • Courtney D. DiNardo,
  • Alan P. Kumar

摘要

Acute myeloid leukaemia (AML) remains a challenging haematological malignancy, with most patients developing resistance to standard-of-care (SOC) treatments. This resistance is often attributed to the overexpression of anti-apoptotic BCL-2 family proteins, which regulate the intrinsic apoptotic pathway by inhibiting pro-apoptotic effector proteins such as BAX and BAK. AML cells exploit this imbalance to evade apoptosis and sustain survival, necessitating the development of novel therapeutic strategies. BH3 mimetics are small-molecule inhibitors targeting the pro-survival BCL-2 family proteins and have emerged as promising agents in patients with AML who are unable to receive high-intensity induction chemotherapy. Co-treatment with the BCL-2-specific inhibitor venetoclax and various SOC therapies has been proven effective, with several combinations now approved by the US Food and Drug Administration for adults with AML who are ≥75 years of age and/or are ineligible for intensive induction chemotherapy, on the basis of improved response rates and survival outcomes compared with the previous SOC. In this Review, we highlight the transformative potential of BH3 mimetics in AML therapy, including ongoing studies investigating novel combination regimens and efforts to further refine treatment strategies, with the ultimate goal of improving outcomes for patients with AML.