NK Cells Can Preferentially Target Prostate Cancer Stem-like Cells via the TRAIL/DR5 Signaling Pathway

Since prostate cancer (PCa) was described as androgen-dependent, the androgen receptor (AR) has become the mainstay of its systemic treatment: androgen deprivation therapy (ADT). Although, through recent years, more potent drugs have been incorporated, this chronic AR signaling inhibition inevitably led the tumor to an incurable phase of castration resistance. However, in the castration-resistant status, PCa cells remain highly dependent on the AR signaling axis, and proof of it is that many men with castration-resistant prostate cancer (CRPC) still respond to newer-generation AR signaling inhibitors (ARSis). Nevertheless, this response is limited in time, and soon, the tumor develops adaptive mechanisms that make it again nonresponsive to these treatments. For this reason, researchers are focused on searching for new alternatives to control these nonresponsive tumors, such as: (1) drugs with a different mechanism of action, (2) combination therapies to boost synergies, and (3) agents or strategies to resensitize tumors to previously addressed targets. Taking advantage of the wide variety of mechanisms that promote persistent or reactivated AR signaling in CRPC, many drugs explore this last interesting behavior. In this article, we will review those strategies and drugs that are able to resensitize cancer cells to previously used treatments through the use of “hinge” treatments with the objective of obtaining an oncological benefit. Some examples are: bipolar androgen therapy (BAT) and drugs such as indomethacin, niclosamide, lapatinib, panobinostat, clomipramine, metformin, and antisense oligonucleotides. All of them have shown, in addition to an inhibitory effect on PCa, the rewarding ability to overcome acquired resistance to antiandrogenic agents in CRPC, resensitizing the tumor cells to previously used ARSis.

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“…Likewise, it has been shown that natural killer (NK) cells target androgen-dependent PCa stem-like cells [ 87 ].…”

Section: Agents and Strategies To Resensitize Crpc To Antiandrogen Th...mentioning

confidence: 99%

Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy

et al. 2023

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“…reported that co-cultured KHYG-1 human NK cells can preferentially target PCSCs via the TRAIL/DR5 signaling pathway. In vitro data showed that KHYG-1 cells could induce more cytotoxicity against LNCaP stem-like cells than androgen-dependent LNCaP cells (normal prostate cancer cells) ( 150 ).…”

Section: Immunotherapymentioning

confidence: 99%

State-of-the-art therapeutic strategies for targeting cancer stem cells in prostate cancer

Ramesh

Selvakumar²,

Ameer³

et al. 2023

Front. Oncol.

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The development of new therapeutic strategies is on the increase for prostate cancer stem cells, owing to current standardized therapies for prostate cancer, including chemotherapy, androgen deprivation therapy (ADT), radiotherapy, and surgery, often failing because of tumor relapse ability. Ultimately, tumor relapse develops into advanced castration-resistant prostate cancer (CRPC), which becomes an irreversible and systemic disease. Hence, early identification of the intracellular components and molecular networks that promote prostate cancer is crucial for disease management and therapeutic intervention. One of the potential therapeutic methods for aggressive prostate cancer is to target prostate cancer stem cells (PCSCs), which appear to be a primary focal point of cancer metastasis and recurrence and are resistant to standardized therapies. PCSCs have also been documented to play a major role in regulating tumorigenesis, sphere formation, and the metastasis ability of prostate cancer with their stemness features. Therefore, the current review highlights the origin and identification of PCSCs and their role in anti-androgen resistance, as well as stemness-related signaling pathways. In addition, the review focuses on the current advanced therapeutic strategies for targeting PCSCs that are helping to prevent prostate cancer initiation and progression, such as microRNAs (miRNAs), nanotechnology, chemotherapy, immunotherapy, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing system, and photothermal ablation (PTA) therapy.

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“…A recent study cocultured human NK cells (KHYG-1) with human prostate cancer stem-like cells. They discovered that NK cells exerted a killing effect by initiating the TRAIL/DR5 cell death pathway [75]. In another study, a selenium-bearing ruthenium complex (RuSe) was designed.…”

Section: Role Of Apoptosis In Prostate Cancermentioning

confidence: 99%

Caspase-Linked Programmed Cell Death in Prostate Cancer: From Apoptosis, Necroptosis, and Pyroptosis to PANoptosis

Zhu,

Liu,

Liu

et al. 2023

Biomolecules

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Prostate cancer (PCa) is a complex disease and the cause of one of the highest cancer-related mortalities in men worldwide. Annually, more than 1.2 million new cases are diagnosed globally, accounting for 7% of newly diagnosed cancers in men. Programmed cell death (PCD) plays an essential role in removing infected, functionally dispensable, or potentially neoplastic cells. Apoptosis is the canonical form of PCD with no inflammatory responses elicited, and the close relationship between apoptosis and PCa has been well studied. Necroptosis and pyroptosis are two lytic forms of PCD that result in the release of intracellular contents, which induce inflammatory responses. An increasing number of studies have confirmed that necroptosis and pyroptosis are also closely related to the occurrence and progression of PCa. Recently, a novel form of PCD named PANoptosis, which is a combination of apoptosis, necroptosis, and pyroptosis, revealed the attached connection among them and may be a promising target for PCa. Apoptosis, necroptosis, pyroptosis, and PANoptosis are good examples to better understand the mechanism underlying PCD in PCa. This review aims to summarize the emerging roles and therapeutic potential of apoptosis, necroptosis, pyroptosis, and PANoptosis in PCa.

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NK Cells Can Preferentially Target Prostate Cancer Stem-like Cells via the TRAIL/DR5 Signaling Pathway

Cited by 10 publications

References 32 publications

Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy

Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy

State-of-the-art therapeutic strategies for targeting cancer stem cells in prostate cancer

Caspase-Linked Programmed Cell Death in Prostate Cancer: From Apoptosis, Necroptosis, and Pyroptosis to PANoptosis

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