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Abstract：
Targeting the intrinsic apoptotic pathway regulated by B-cell lymphoma-2 (BCL-2) antiapoptotic proteins can overcome the evasion of apoptosis in cancer cells. BCL-2 inhibitors have evolved into an important means of treating cancers by inducing tumor cell apoptosis. As the most extensively investigated BCL-2 inhibitor, venetoclax is highly selective for BCL-2 and can effectively inhibit tumor survival. Its emergence and development have significantly influenced the therapeutic landscape of hematological malignancies, especially in chronic lymphocytic leukemia and acute myeloid leukemia, in which it has been clearly incorporated into the recommended treatment regimens. In addition, the considerable efficacy of venetoclax in combination with other agents has been demonstrated in relapsed and refractory multiple myeloma and certain lymphomas. Although venetoclax plays a prominent antitumor role in preclinical experiments and clinical trials, large individual differences in treatment outcomes have been characterized in real-world patient populations, and reduced drug sensitivity will lead to disease recurrence or progression. The therapeutic efficacy may vary widely in patients with different molecular characteristics, and key genetic mutations potentially result in differential sensitivities to venetoclax. The identification and validation of more novel biomarkers are required to accurately predict the effectiveness of BCL-2 inhibition therapy. Furthermore, we summarize the recent research progress relating to the use of BCL-2 inhibitors in solid tumor treatment and demonstrate that a wealth of preclinical models have shown promising results through combination therapies. The applications of venetoclax in solid tumors warrant further clinical investigation to define its prospects.
摘要：
靶向由B细胞淋巴瘤-2（BCL-2）抗凋亡蛋白调节的内在凋亡途径可以克服癌细胞中凋亡的逃避。BCL-2抑制剂已经发展成为通过诱导肿瘤细胞凋亡来治疗癌症的重要手段。作为研究最广泛的BCL-2抑制剂，venetoclax对BCL-2具有高度选择性，可以有效抑制肿瘤的存活。它的出现和发展对血液恶性肿瘤的治疗前景产生了重大影响，尤其是慢性淋巴细胞白血病和急性髓细胞性白血病，其中已明确纳入推荐的治疗方案。此外,在复发和难治性多发性骨髓瘤和某些淋巴瘤中，已证明维奈托克与其他药物联合使用具有相当大的疗效。尽管维奈托克在临床前实验和临床试验中发挥着重要的抗肿瘤作用，在现实世界的患者人群中，治疗结果存在很大的个体差异，药物敏感性降低会导致疾病复发或进展。在具有不同分子特征的患者中，治疗效果可能差异很大。和关键的基因突变可能导致对维内克的不同敏感性。为了准确预测BCL-2抑制疗法的有效性，需要更多新型生物标志物的鉴定和验证。此外，我们总结了BCL-2抑制剂在实体瘤治疗中的应用的最新研究进展,并证明大量临床前模型通过联合治疗显示了有希望的结果.维奈托克在实体瘤中的应用值得进一步的临床研究以确定其前景。
