Translating p53-based therapies for cancer into the clinic

Peuget, Sylvain; Zhou, Xiaolei; Selivanova, Galina

doi:10.1038/s41568-023-00658-3

Cited by 31 publications

(5 citation statements)

References 220 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another approach to preserve wild-type p53 is the inhibition of proteins that lead to its degradation, such as MDM2 and MDMX. Several clinical trials using drugs targeting these molecules have been concluded with promising results; however, no MDM2 or MDMX inhibitor has been approved by the FDA [ 37 ].…”

Section: Crosstalk Between Apoptotic and Immune Cells Affects The Fat...mentioning

confidence: 99%

Apoptosis, a Metabolic “Head-to-Head” between Tumor and T Cells: Implications for Immunotherapy

Franzese,

Ancona,

Bianchi

et al. 2024

Cells

View full text Add to dashboard Cite

Induction of apoptosis represents a promising therapeutic approach to drive tumor cells to death. However, this poses challenges due to the intricate nature of cancer biology and the mechanisms employed by cancer cells to survive and escape immune surveillance. Furthermore, molecules released from apoptotic cells and phagocytes in the tumor microenvironment (TME) can facilitate cancer progression and immune evasion. Apoptosis is also a pivotal mechanism in modulating the strength and duration of anti-tumor T-cell responses. Combined strategies including molecular targeting of apoptosis, promoting immunogenic cell death, modulating immunosuppressive cells, and affecting energy pathways can potentially overcome resistance and enhance therapeutic outcomes. Thus, an effective approach for targeting apoptosis within the TME should delicately balance the selective induction of apoptosis in tumor cells, while safeguarding survival, metabolic changes, and functionality of T cells targeting crucial molecular pathways involved in T-cell apoptosis regulation. Enhancing the persistence and effectiveness of T cells may bolster a more resilient and enduring anti-tumor immune response, ultimately advancing therapeutic outcomes in cancer treatment. This review delves into the pivotal topics of this multifaceted issue and suggests drugs and druggable targets for possible combined therapies.

show abstract

Section: Crosstalk Between Apoptotic and Immune Cells Affects The Fat...mentioning

confidence: 99%

Apoptosis, a Metabolic “Head-to-Head” between Tumor and T Cells: Implications for Immunotherapy

Franzese,

Ancona,

Bianchi

et al. 2024

Cells

View full text Add to dashboard Cite

show abstract

“…Methods such as blocking murine double minute 2 (MDM2), as well as restoring dysfunctional p53 are being attempted. 397 It is expected to identify more promising targets and accordingly develop robust agents in the future.…”

Section: Cancer Risk Prediction and Intervention Strategiesmentioning

confidence: 99%

Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets

Zhang,

Xiao,

et al. 2024

Sig Transduct Target Ther

View full text Add to dashboard Cite

Tumorigenesis is a multistep process, with oncogenic mutations in a normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic mutations and clonal expansion in normal tissues, their transformation into cancer remains a rare event, indicating the presence of additional driver events for progression to an irreversible, highly heterogeneous, and invasive lesion. Recently, researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution, independently of inducing mutations. Additionally, clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into tumors. However, the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully understood. In this review, we summarize the genetic, epigenetic, and external driver events, and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution. A deeper understanding of the earliest molecular events holds promise for translational applications, predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.

show abstract

“…As a transcription factor, p53 activates or represses the transcription of multiple downstream target genes to perform its function. 53 The p53 can transcriptionally repress SLC7A11 expression at the transcriptional level, thereby promoting the occurrence of ferroptosis in cells. 54 Also, p53 releases Arachidonate 12-lipoxygenase (ALOX12).…”

Section: Ferroptosis Mechanismmentioning

confidence: 99%

Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

Luo,

Bai,

Zhang

et al. 2024

DDDT

View full text Add to dashboard Cite

Translating p53-based therapies for cancer into the clinic

Cited by 31 publications

References 220 publications

Apoptosis, a Metabolic “Head-to-Head” between Tumor and T Cells: Implications for Immunotherapy

Apoptosis, a Metabolic “Head-to-Head” between Tumor and T Cells: Implications for Immunotherapy

Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets

Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

Contact Info

Product

Resources

About