The B-cell lymphoma 2 (BCL-2) protein family members are key proteins that control the process of programmed cell death, known as apoptosis. In several hematologic malignancies, abnormal expression of pro-survival or pro-apoptotic members of the BCL-2 protein family have the potential to accelerate the proliferation of neoplastic cells and provide resistance to therapeutic interventions. Fortunately, rapid progress has been made in understanding how the different subgroups of the BCL-2 family proteins interact with each other and deregulate hematologic malignancies, and new paths for clinical translation continue to be identified. This understanding has allowed the production of Venetoclax, the first selective BCL-2 inhibitor and the first member of a novel class of drugs known as BH3-mimetics.

Currently, Venetoclax is commonly used for treating patients with chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). Additionally, it is being studied for an extensive number of blood neoplasms, including but not limited to multiple myeloma, AL amyloidosis, and B and T-cell lymphomas. The BCL-2 inhibition in the clinical practice of CLL and particularly AML marked a significant paradigm shift in the field. As we learn more about BCL-2 inhibitor combinations, the treatment algorithm for CLL and AML will keep changing in the future years. However, several questions will still need to be addressed, such as identifying the populations that benefit the most from these combinations, optimizing the sequencing of these inhibitors in combination with other therapeutics, and understanding the mechanism of resistance development. While the introduction of Venetoclax has transformed the treatment of patients with AML, the emergence of resistance poses a significant obstacle in attaining prolonged periods of remission and overall survival for the majority of patients.

The main objective of this Research Topic is to encourage research papers that investigate these questions and bring novel and impactful knowledge for more effective clinical treatments utilizing BCL-2 inhibitors.

We encourage the contributing authors to submit their valuable work covering original research, conducted clinical trials, insightful case reports, and comprehensive review articles. The authors are advised to direct their efforts on submissions that principally address the following subtopics:

• Investigate and evaluate the effectiveness and safety profile of BCL-2 inhibition when administered in combination with various agents in both frontline and relapsed/refractory settings of CLL.

• Clarify the function of BCL-2 inhibition and assess available data regarding its use in the treatment of elderly and fit, young patients with AML.

• Examine the predictive factors of response and identify the mechanism of resistance to BCL-2 inhibitors.

• Evaluate the rationale for the development of novel BCL-2 inhibitors and provide efficacy data applicable to any clinical context involving hematological neoplasms.

Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.

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Frontiers in Oncology

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