Behind the Adaptive and Resistance Mechanisms of Cancer Stem Cells to TRAIL

Quiroz-Reyes, Adriana G.; Delgado-Gonzalez, Paulina; Islas, Jose Francisco; Gallegos, Juan Luis Delgado; Martínez Garza, Javier Humberto; Garza-Treviño, Elsa N.

doi:10.3390/pharmaceutics13071062

Cited by 13 publications

(9 citation statements)

References 115 publications

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“…While not yet studied in breast cancer, TRAIL may also have pro-tumorigenic effects on immune cells. TRAIL can potentiates the activity of Treg cells which are well-known contributors to immune escape of tumors [ 247 ]. Tregs secrete various anti-inflammatory cytokines such as TGFβ, IL-10, and IL-35 which inhibits anti-tumor immunity by suppressing CTL activity and antigen presentation by DCs [ 248 ].…”

Section: Strategies To Improve Dr Agonists In Patients With Breast Ca...mentioning

confidence: 99%

Targeting TRAIL Death Receptors in Triple-Negative Breast Cancers: Challenges and Strategies for Cancer Therapy

Kundu

Greer

Dine

et al. 2022

Cells

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The tumor necrosis factor (TNF) superfamily member TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells via death receptor (DR) activation with little toxicity to normal cells or tissues. The selectivity for activating apoptosis in cancer cells confers an ideal therapeutic characteristic to TRAIL, which has led to the development and clinical testing of many DR agonists. However, TRAIL/DR targeting therapies have been widely ineffective in clinical trials of various malignancies for reasons that remain poorly understood. Triple negative breast cancer (TNBC) has the worst prognosis among breast cancers. Targeting the TRAIL DR pathway has shown notable efficacy in a subset of TNBC in preclinical models but again has not shown appreciable activity in clinical trials. In this review, we will discuss the signaling components and mechanisms governing TRAIL pathway activation and clinical trial findings discussed with a focus on TNBC. Challenges and potential solutions for using DR agonists in the clinic are also discussed, including consideration of the pharmacokinetic and pharmacodynamic properties of DR agonists, patient selection by predictive biomarkers, and potential combination therapies. Moreover, recent findings on the impact of TRAIL treatment on the immune response, as well as novel strategies to address those challenges, are discussed.

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Section: Strategies To Improve Dr Agonists In Patients With Breast Ca...mentioning

confidence: 99%

Targeting TRAIL Death Receptors in Triple-Negative Breast Cancers: Challenges and Strategies for Cancer Therapy

Kundu

Greer

Dine

et al. 2022

Cells

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“…The tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) can form a homotrimer with its receptor to initiate and target apoptosis in tumor cells. Numerous recent studies have been conducted on TRAIL [ 112 ]. For example, Feng et al used a targeted drug delivery system with promising results, showing that TRAIL enhanced the targeting ability of nanoparticles and acted synergistically with DOX-inhibiting tumor cells [ 113 ].…”

Section: Natural Products Overcome Autophagy-mediated Tumor Drug Resi...mentioning

confidence: 99%

Focusing on the Role of Natural Products in Overcoming Cancer Drug Resistance: An Autophagy-Based Perspective

Yao

Feng

et al. 2022

Biomolecules

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Autophagy is a critical cellular adaptive response in tumor formation. Nutritional deficiency and hypoxia exacerbate autophagic flux in established malignancies, promoting tumor cell proliferation, migration, metastasis, and resistance to therapeutic interventions. Pro-survival autophagy inhibition may be a promising treatment option for advanced cancer. Furthermore, excessive or persistent autophagy is cytotoxic, resulting in tumor cell death. Targeted autophagy activation has also shown significant promise in the fight against tumor drug resistance. Several research groups have examined the ability of natural products (NPs) such as alkaloids, terpenoids, polyphenols, and anthraquinones to serve as autophagy inhibitors or activators. The data support the capacity of NPs that promote lethal autophagy or inhibit pro-survival autophagy from being employed against tumor drug resistance. This paper discusses the potential applications of NPs that regulate autophagy in the fight against tumor drug resistance, some limitations of the current studies, and future research needs and priorities.

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“…CSCs are also known for their therapy resistance. For instance, as reviewed by Quiroz-Reyes et al, CSCs can quickly develop adaptative evasion mechanisms for Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) apoptosis [ 13 ]. Several CSC biomarkers have been identified with useful applications to diagnosis, therapy, and prognosis.…”

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confidence: 99%