Combination strategies to overcome resistance to the BCL2 inhibitor venetoclax in hematologic malignancies

Yue, Xiumei; Chen, Qingxiao; He, Jingsong

doi:10.1186/s12935-020-01614-z

Cited by 39 publications

(43 citation statements)

References 113 publications

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“…Apoptosis is a form of programmed cell death that maintains homeostasis in the body ( Yue et al, 2020 ). Unsurprisingly, malignant cells often acquire the ability to evade apoptosis.…”

Section: Regulation Of Tumorigenesis and Progressionmentioning

confidence: 99%

LncRNA GACAT3: A Promising Biomarker and Therapeutic Target in Human Cancers

Yuan

Dong

Shen

2022

Front. Cell Dev. Biol.

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Long non-coding RNAs (lncRNAs) are a class of functional RNA molecules that do not encode proteins and are composed of more than 200 nucleotides. LncRNAs play important roles in epigenetic and gene expression regulation. The oncogenic lncRNA GACAT3 was recently discovered to be dysregulated in many tumors. Aberrant expression of GACAT3 contributes to clinical characteristics and regulates multiple oncogenic processes. The association of GACAT3 with a variety of tumors makes it a promising biomarker for diagnosis, prognosis, and targeted therapy. In this review, we integrate the current understanding of the pathological features, biological functions, and molecular mechanisms of GACAT3 in cancer. Additionally, we provide insight into the utility of GACAT3 as an effective diagnostic and prognostic marker for specific tumors, which offers novel opportunities for targeted therapeutic intervention.

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“…Apoptosis is a form of programmed cell death that maintains homeostasis in the body ( Yue et al, 2020 ). Unsurprisingly, malignant cells often acquire the ability to evade apoptosis.…”

Section: Regulation Of Tumorigenesis and Progressionmentioning

confidence: 99%

LncRNA GACAT3: A Promising Biomarker and Therapeutic Target in Human Cancers

Yuan

Dong

Shen

2022

Front. Cell Dev. Biol.

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“…Similarly, mutations in BCL2, detectable months earlier than clinical progression using droplet digital PCR, have been shown to decrease the efficacy of venetoclax [90]. Activated T-cells produce IL-4 and IL-21 that can stimulate the CD40-CD40L interaction and increase the expression of the anti-apoptotic factor BCL-xL, among other factors [91].…”

Section: Role Of the Immune System In Resistance To Treatmentmentioning

confidence: 99%

“…Combination of ibrutinib and venetoclax would reduce the probabilities of proliferation of clones with resistant mutations in both pathways simultaneously. Additionally, it has been shown that microenvironment cytokines (IL-10, sCD40L or CpG-ODNs) can significantly reduce the synergy of the combination in an NF-κB-dependent manner [91,92].…”

Section: Role Of the Immune System In Resistance To Treatmentmentioning

confidence: 99%

Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively

Moreno¹,

Muñoz

Terol

et al. 2021

J Exp Clin Cancer Res

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Chronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by uncontrolled proliferation of B-cells and severe immune dysfunction. Chemo(immuno)therapies (CIT) have traditionally aimed to reduce tumor burden without fully understanding their effects on the immune system. As a consequence, CIT are usually associated with higher risk of infections, secondary neoplasms and autoimmune disorders. A better understanding of the biology of the disease has led to the development of therapeutic strategies which not only act against malignant B-cells but also reactivate and enhance the patient’s own anti-tumor immune response. Here, we review the current understanding of the underlying interplay between the malignant cells and non-malignant immune cells that may promote tumor survival and proliferation. In addition, we review the available evidence on how different treatment options for CLL including CIT regimens, small molecular inhibitors (i.e, BTK inhibitors, PI3K inhibitors, BCL-2 inhibitors) and T-cell therapies, affect the immune system and their clinical consequences. Finally, we propose that a dual therapeutic approach, acting directly against malignant B-cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL.

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“…BCL2 family proteins control the intrinsic apoptotic pathway, and venetoclax is a novel, oral BH3-mimetic and highly selective BCL2 inhibitor that is very effective in overcoming the anti-apoptotic effect of BCL2. Venetoclax has been approved in CLL both in the relapsed [26] and frontline setting [27] , and it is also being studied in the frontline setting for double expressor DLBCL [28] and the relapsed setting for mantle cell lymphoma (MCL) [29] . There are a variety of mechanisms for resistance to venetoclax.…”

Section: Resistance To Targeted Therapiesmentioning

confidence: 99%

Barriers to achieving a cure in lymphoma

Kambhampati¹,

Song²,

Herrera³

et al. 2021

CDR

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Lymphoma is a diverse disease with a variety of different subtypes, each characterized by unique pathophysiology, tumor microenvironment, and underlying signaling pathways leading to oncogenesis. With our increasing understanding of the molecular biology of lymphoma, there have been a number of novel targeted therapies and immunotherapy approaches that have been developed for the treatment of this complex disease. Despite rapid progress in the field, however, many patients still relapse largely due to the development of drug resistance to these therapies. A better understanding of the mechanisms underlying resistance is needed to develop more novel treatment strategies that circumvent these mechanisms and design better treatment algorithms that personalize therapies to patients and sequence these therapies in the most optimal manner. This review focuses on the recent advances in therapies in lymphoma, including targeted therapies, monoclonal antibodies, antibody-drug conjugates, cellular therapy, bispecific antibodies, and checkpoint inhibitors. We discuss the genetic and cellular principles of drug resistance that span across all the therapies, as well as some of the unique mechanisms of resistance that are specific to these individual classes of therapies and the strategies that have been developed to address these modes of resistance.

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Combination strategies to overcome resistance to the BCL2 inhibitor venetoclax in hematologic malignancies

Cited by 39 publications

References 113 publications

LncRNA GACAT3: A Promising Biomarker and Therapeutic Target in Human Cancers

LncRNA GACAT3: A Promising Biomarker and Therapeutic Target in Human Cancers

Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively

Barriers to achieving a cure in lymphoma

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