2018
DOI: 10.3390/ijms19123950
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Bcl-2 Inhibition to Overcome Resistance to Chemo- and Immunotherapy

Abstract: According to the World Health Organization (WHO), cancer is a leading cause of death worldwide. The identification of novel targets for cancer treatment is an area of intense work that has led Bcl-2 over-expression to be proposed as one of the hallmarks of cancer and Bcl-2 inhibition as a promising strategy for cancer treatment. In this review, we describe the different pathways related to programmed cell death, the role of Bcl-2 family members in apoptosis resistance to anti-cancer treatments, and the potenti… Show more

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Cited by 119 publications
(96 citation statements)
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“…These findings have been the basis for the development of different modalities of anticancer immunotherapy, including tumor-targeting immunotherapies, oncolytic viruses, anticancer vaccines, or adoptive cell immunotherapies [24] that are designed to target tumor cells and work with the immune system at different levels ( Figure 2). As a result of the great success achieved in different studies and trials that demonstrate the efficacy of immunotherapies not only against primary tumors, but also preventing metastasis and recurrence [25], cancer immunotherapy has become the fourth pillar of cancer care, complementing surgery, cytotoxic therapy, and radiotherapy [26].…”
Section: Changes In Tumor Cellsmentioning
confidence: 99%
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“…These findings have been the basis for the development of different modalities of anticancer immunotherapy, including tumor-targeting immunotherapies, oncolytic viruses, anticancer vaccines, or adoptive cell immunotherapies [24] that are designed to target tumor cells and work with the immune system at different levels ( Figure 2). As a result of the great success achieved in different studies and trials that demonstrate the efficacy of immunotherapies not only against primary tumors, but also preventing metastasis and recurrence [25], cancer immunotherapy has become the fourth pillar of cancer care, complementing surgery, cytotoxic therapy, and radiotherapy [26].…”
Section: Changes In Tumor Cellsmentioning
confidence: 99%
“…Another major impediment to immunotherapy success in breast cancer patients is the selection of apoptosis-resistant cells, which constitutes one of the hallmarks of cancer [17]. Since both chemo-and immunotherapies directly or indirectly activate the cellular apoptosis machinery, tumor sensitivity to anti-cancer treatments will significantly depend on the level of expression of anti-apoptotic proteins [24] in general and, more specifically, on the existence of a pro-survival profile characterized by an increased ratio between anti-/pro-apoptotic proteins [24,90,91].…”
Section: Changes In Breast Tumor Cellsmentioning
confidence: 99%
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“…In the oncology setting, the prosurvival BCL-2 family proteins have been identified as key factors in the resistance of many tumor cells to death (35)(36)(37)(38). BCL-2 antagonists, such as , have been developed as cancer therapies that aim to directly promote the apoptosis of tumor cells, which often overexpress BCL-2 (35)(36)(37)(38)(39)(40). By adding ABT-199 to our kick-and-kill cocultures, we were able to achieve the reductions in ex vivo HIV reservoirs that we have been unable to achieve with CTL and LRAs alone.…”
Section: Introductionmentioning
confidence: 99%
“…As shown in Figure 5(C,D), DOX caused an upregulation of protein expression of Bax and Bcl-2 by 33% and 39%, respectively. It is well documented that upregulating anti-apoptotic protein Bcl-2 is a common mechanism in tumours to evade apoptosis [31]. With the combination of anti-inflammatory ingredient, KIR, the protein expression of Bax further increased by 85%, while Bcl-2 protein expression was significantly decreased by 63%.…”
Section: In Vitro Anti-tumour Therapymentioning
confidence: 99%