Cancer-related Molecular Pathways

Experiment-anchored abundance-coverage frontiers define conditional RHSVV exposure requirements in TP53-missense tumors

Experiment-anchored sweep of p53 abundance thresholds in CPTAC TP53-missense tumors maps how much RHSVV exposure contrast is needed as target coverage falls.

Mitotic bypass and continued endocycling promote cancer cell survival after genotoxic chemotherapy

This study shows cancer cells survive genotoxic chemotherapy by entering a drug-tolerant persister state involving mitotic bypass and endocycling, which can be targeted by inhibiting WEE1 or Myt1.

E2F3 amplification primes bladder cancer cells for premature mitosis.

This study shows E2F3 amplification in bladder cancer cells leads to premature mitosis, which can be targeted by G2/M checkpoint inhibitors.

Dual contributions of Xrp1 to genome integrity through the DNA damage response and cell competition

This paper shows Xrp1 contributes to genome integrity through p53-dependent DNA damage response and p53-independent cell competition in Drosophila.

CIZ1 regulates G1 length and the CDK threshold for initiation of DNA replication to prevent DNA replication stress

This study shows that CIZ1 regulates G1 length and the CDK threshold for DNA replication initiation, preventing DNA replication stress and genome instability.

Thermodynamic Insights into the WT and Y220C TP53 DBDs Reveals that the Oncogenic Y220C Variant is a Loss of Function Mutation for Zn2+-binding at Physiological Temperature

The paper investigates the thermodynamic effects of the Y220C TP53 mutation on Zn2+-binding and shows that Rezatapopt restores Zn2+-affinity through two pathways.

Cdk1 and PP2A constitute a molecular switch controlling orderly degradation of atypical E2Fs

The paper identifies Cdk1 and PP2A as a molecular switch that controls the degradation of E2F7 and E2F8, ensuring timely transcriptional reprogramming during the cell cycle.

TP53-META, a meta-analysis tool for comparative transcriptomics of TP53 dependency: Examples from target silencing and liver fibrosis

TP53-META enables meta-analysis of TP53-related gene expression datasets to identify dependency patterns in transcriptomic changes across different conditions.

Distinct genomic and immunologic tumor evolution in germline TP53-driven breast cancers

This study compares genomic and immunologic features of germline TP53-driven breast cancers to sporadic breast cancers, finding distinct patterns of genomic instability and immune infiltration.

Variation at the R181 residue of p53 confers loss of p53 DNA binding cooperativity with the retention of mitochondrial-associated apoptosis

This study shows that p53 variants with R181 mutations retain mitochondrial apoptosis function but lose DNA binding cooperativity, leading to reduced cancer risk.

Activating p53Y220C with a Mutant-Specific Small Molecule

This paper develops a small molecule, TRAP-1, that activates mutant p53 by forming a ternary complex with BRD4, leading to p53 target gene upregulation and inhibition of cancer cell growth.

THE FAM53C/DYRK1A axis regulates the G1/S transition of the cell cycle

This study identifies FAM53C as a regulator of the G1/S cell cycle transition, showing it interacts with DYRK1A and affects cell cycle progression in cultured cells and organoids.

MDM2 stabilization of Notch intracellular domain upon DNA damage plays a major role in non-small cell lung carcinoma response to platinum chemotherapy

This study identifies MDM2 stabilization of NICD in response to platinum chemotherapy in NSCLC, showing that targeting MDM2 and NICD improves survival and reduces tumor growth.

Noc1 downregulation induces nucleolar stress and upregulates p53 isoforms, with a robust increase of the truncated p53E isoform in Drosophila wing discs

The paper shows that Noc1 downregulation in Drosophila causes nucleolar stress, increases p53 levels, and specifically upregulates the truncated p53E isoform, which may modulate apoptosis.

In-Silico Characterization of TP53 Splice Mutations in Somatic and Germline Tumours

This study analyzes TP53 splice site mutations in somatic and germline tumors, finding distinct transcriptional effects and clinical outcomes.

Mice carrying nonsense mutant p53 develop frequent multicentric or metastatic tumors

This paper develops a mouse model with a TP53 nonsense mutation to study tumor development and finds it leads to frequent multicentric or metastatic tumors.

Neoantigenic properties of TP53 variants modify cancer risk in individuals with Li-Fraumeni syndrome

The paper analyzes how neoantigenic properties of TP53 variants correlate with cancer risk and presentation in Li-Fraumeni syndrome carriers.

p53 protein abundance is a therapeutic window across TP53 mutant cancers and is targetable with proximity inducing small molecules

The paper shows that p53 protein abundance in TP53 mutant cancers can be exploited to selectively kill these cells using proximity-inducing small molecules.

Human Papilloma Virus does not fully inactivate p53 cellular activity in HNSCC

This study shows that p53 activity persists in HPV+ HNSCC tumors with WT TP53, leading to better survival and therapeutic vulnerabilities.

Mutant p53 regulates cancer cell invasion in complex three-dimensional environments through mevalonate pathway-dependent Rho/ROCK signaling.

This study shows mutant p53 promotes cancer cell invasion in 3D environments via mevalonate pathway-dependent Rho/ROCK signaling and ECM reorganization.

Differential splice isoforms of mouse CDK2 play functionally redundant roles during mitotic and meiotic division

This study shows that CDK2L and CDK2S isoforms are functionally redundant in supporting both mitotic and meiotic divisions in mice.

Targeting MDM2 homodimer and heterodimer disruption with DRx-098D in TP53 wild-type and mutant cancer cells

This study shows DRx-098D, a peptide disrupting MDM2 dimerisation, effectively inhibits cancer cell growth in TP53 wild-type and mutant cell lines, outperforming Idasanutlin in TP53 null cells.

Cyclin A/B RxL Macrocyclic Inhibitors to Treat Cancers with High E2F Activity

This paper develops cyclin A/B macrocyclic inhibitors that induce apoptosis in cancers with high E2F activity by blocking RxL-mediated interactions, showing efficacy in SCLC models.

Regulation of the MDM2-p53 Nexus by a Nuclear Phosphoinositide and Small Heat Shock Protein Complex

This study identifies a role for nuclear phosphoinositides in regulating MDM2 stability and function through interactions with small heat shock proteins, offering a new therapeutic target in cancer.

Transcriptional repression of SOX2 by p53 in cancer cells regulates cell identity and migration

This paper shows that TP53 represses SOX2 in cancer cells, affecting cell identity and migration, with implications for metastasis in breast cancer.

Integrative multiomic approaches reveal ZMAT3 and p21 as conserved hubs in the p53 tumor suppression network

The paper identifies ZMAT3 and CDKN1A as key hubs in the p53 tumor suppression network through integrative multiomic analyses in a mouse model.

Δ133p53α and Δ160p53α isoforms of the tumor suppressor protein p53 exert dominant-negative effect primarily by co-aggregation

This study identifies that Δ133p53α and Δ160p53α isoforms exert a dominant-negative effect on p53 by co-aggregating with full-length p53, disrupting its function.

Oncogenic and teratogenic effects of Trp53Y217C, an inflammation-prone mouse model of the human hotspot mutant TP53Y220C

This study shows that the p53Y217C mutation causes inflammation, leading to oncogenic effects in male mice and teratogenic effects in female mice, with anti-inflammatory treatment improving female survival.

Mis-splicing Drives Loss of Function of p53E224D Point Mutation

The paper investigates a p53 mutation that causes mis-splicing and loss of function in vitro and in vivo, challenging the classical view of p53 tumor suppression.

Pulsed stimuli entrain p53 to synchronize single cells and modulate cell-fate determination

This study shows that p53 oscillations can be entrained by periodic DNA damage stimuli, leading to synchronized cell responses and altered cell-fate outcomes.