Due to their key role in the pathogenesis of cancer through the regulation of apoptosis, the B-cell leukemia/lymphoma-2 (BCL-2) family proteins have been an attractive target for cancer therapy for the past decades. Throughout the years, many Bcl-2 family inhibitors have been developed, with Venetoclax being now successfully used in treating hematological malignancies. Although their effectiveness in the treatment of solid tumors is yet to be established, some preclinical evidence indicates their possible clinical application. This review aims to summarize current data from completed clinical trials that used Bcl-2 protein family inhibitors as monotherapy or in combination with other agents for the treatment of solid malignancies. We managed to include clinical trials of various phases which analyze the pharmacokinetics and pharmacodynamics of the drugs, as well as the effectiveness and adverse effects. Active and recruiting clinical trials are also briefly presented and future prospects and challenges are discussed.

Introduction Chimeric Antigen Receptor (CAR)-T cell therapy is a form of adoptive cell therapy that has demonstrated tremendous results in the treatment of hematopoietic malignancies, leading to the US Food and Drug Administration (FDA) approval of four CD19-targeted CAR-T cell products. With the unprecedented success of CAR-T cell therapy in hematological malignancies, hundreds of preclinical studies and clinical trials are currently undergoing to explore the translation of this treatment to solid tumors. However, the clinical experience in non-hematologic malignancies has been less encouraging, with only a few patients achieving complete responses. Tumor-associated antigen heterogeneity, inefficient CAR-T cell trafficking and the immunosuppressive tumor microenvironment are considered as the most pivotal roadblocks in solid tumor CAR-T cell therapy. Materials and methods We reviewed the relevant literature/clinical trials for CAR-T cell immunotherapy for solid tumors from Pubmed and ClinicalTrials.gov. Conclusion Herein, we provide an update on solid tumor CAR-T cell clinical trials, focusing on the studies with published results. We further discuss some of the key hurdles that CAR-T cell therapy is encountering for solid tumor treatment as well as the strategies that are exploited to overcome these obstacles.