News - TP53 wild-type

ANGEL2 modulates wildtype TP53 translation and doxorubicin chemosensitivity in colon cancer. (PubMed, Mol Cancer Res)

Loss of ANGEL2 in cancer cell lines resulted in increased 2D and 3D spheroid cell growth, and resistance to doxorubicin and etoposide. Together, we conclude that ANGEL2 modulates the EIF4E-RBM38 complex to enhance wildtype TP53 translation, and further, the Pep7 peptide may be explored as a therapeutic strategy for cancers which harbor wildtype TP53 expression. Implications: Loss of ANGEL2 contributes to decreased wildtype TP53 translation promoting doxorubicin resistance which can be rescued via an ANGEL2-derived peptide.

3 days ago

Journal

TP53 (Tumor protein P53) • RBM38 (RNA Binding Motif Protein 38)

TP53 wild-type

doxorubicin hydrochloride • etoposide IV

Ganglioglioma in mature cystic teratoma of the ovary: Case report and review of the literature. (PubMed, Gynecol Oncol Rep)

Ganglioglioma arising in mature cystic teratoma of the ovary is an extremely rare tumor. The description of cases is crucial for making the correct diagnosis and developing an effective treatment strategy for pathologists and clinical doctors.

6 days ago

Journal

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CD34 (CD34 molecule) • NES (Nestin) • GFAP (Glial Fibrillary Acidic Protein) • OLIG2 (Oligodendrocyte Transcription Factor 2)

BRAF V600E • TP53 wild-type

Immunotherapy and PARP inhibitors as first-line treatment in endometrial cancer: A systematic review and network meta-analysis. (PubMed, Eur J Cancer)

The addition of the combination of ICI and PARPi to platinum-based chemotherapy provides greatest benefit to p53-abnormal MMRp patients. PD-L1 is a potentially useful biomarker with PD-L1-positive tumors more likely to respond to ICI. Implementation of biomarkers is crucial to redefine the treatment paradigm in a/rEC.

7 days ago

Retrospective data • Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53)

PD-L1 expression • TP53 wild-type

Targeting the MDM2-MDM4 interaction interface reveals an otherwise therapeutically active wild-type p53 in colorectal cancer. (PubMed, Mol Oncol)

These data indicate that targeting the MDM2/MDM4 interaction region provides a different route for wild-type p53 reactivation in human tumors, potentially reducing toxicity to proliferating nontumor tissue. The development of a PLGA/Pep3S formulation represents a promising approach for therapeutic purposes.

9 days ago

Journal

MDM2 (E3 ubiquitin protein ligase) • MDM4 (The mouse double minute 4) • MIR34A (MicroRNA 34a-5p) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)

TP53 wild-type

10d

Impact of genetic mutations on prognosis and chemotherapy efficacy in advanced appendiceal carcinoma: insights from the nationwide Japanese comprehensive genomic profiling test database. (PubMed, Int J Clin Oncol)

This study suggested that the genetic mutations influenced the prognosis and chemotherapy efficacy in AC.

10 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • SMAD4 (SMAD family member 4) • GNAS (GNAS Complex Locus)

TP53 mutation • KRAS mutation • TP53 wild-type • KRAS wild-type

oxaliplatin

11d

Elucidating prognostic significance of purine metabolism in colorectal cancer through integrating data from transcriptomic, immunohistochemical, and single-cell RNA sequencing analysis. (PubMed, Mol Oncol)

Despite the reversible nature of purine metabolism reactions, we demonstrated a consistent directional expression of these five prognostic purine metabolism-related proteins in CRC tissues. We suggest that alterations in purine metabolism could serve as a clinically useful prognostic marker in CRC.

11 days ago

Journal

TP53 (Tumor protein P53)

TP53 mutation • TP53 wild-type

11d

Association between gene mutations and outcomes in Japanese high-risk AML patients: a phase 1/2 study of NS-87/CPX-351. (PubMed, Int J Hematol)

While NS-87/CPX-351 achieved remission even in patients with TP53 mutations, relapse risk was higher in these patients. Therefore, it is advisable to consider treatment strategies such as early transplantation after achieving remission with NS-87/CPX-351, especially in patients with TP53 mutations.

11 days ago

P1/2 data • Journal

TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

TP53 mutation • NRAS mutation • TP53 wild-type • TET2 mutation

Vyxeos (cytarabine/daunorubicin liposomal formulation)

12d

Improving pre-operative binary grading: relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma. (PubMed, Int J Gynecol Cancer)

The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.

12 days ago

Journal

TP53 (Tumor protein P53) • PGR (Progesterone receptor)

TP53 wild-type

12d

A CEBPB/IL-1β/TNF-α Feedback Loop Drives Drug Resistance to Venetoclax and MDM2 Inhibitors in Monocytic Leukemia. (PubMed, Blood)

A combination of venetoclax/ idasanutlin with inhibitors that block IL-1/TNF-α pathway, demonstrate synergistic cytotoxicity in M4/M5 AML. As such, we uncovered a targetable positive feedback loop involving CEBPB, IL-1/TNF-α, and monocyte differentiation in M4/M5 leukemia, which promotes both intrinsic and extrinsic drug resistance, along with drug-induced protection against venetoclax and MDM2 inhibitors.

12 days ago

Journal

TP53 (Tumor protein P53) • MCL1 (Myeloid cell leukemia 1) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • BCL2A1 (BCL2 Related Protein A1) • CASP6 (Caspase 6, apoptosis-related cysteine peptidase) • IL1B (Interleukin 1, beta)

TP53 wild-type

Venclexta (venetoclax) • idasanutlin (RG7388)

13d

Radiomic Analysis of Magnetic Resonance Imaging for Breast Cancer with TP53 Mutation: A Single Center Study. (PubMed, Diagnostics (Basel))

TP53 mutations in breast cancer can be predicted using MRI-derived radiomic analysis. Further research is needed to assess whether radiomics can help guide treatment decisions in clinical practice.

13 days ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53)

HER-2 positive • TP53 mutation • HER-2 mutation • TP53 wild-type

13d

Long term results of venetoclax combined with FLAG-IDA induction and consolidation for newly diagnosed and relapsed or refractory acute myeloid leukemia. (PubMed, Leukemia)

Infectious and hematologic adverse events were common, with low 30- and 60-day mortality similar to other intensive chemotherapy regimens. FLAG-IDA + VEN is effective for remission induction in both ND and RR AML.ClinicalTrials.gov Identifier: NCT03214562.

13 days ago

Journal

TP53 (Tumor protein P53)

TP53 wild-type

Venclexta (venetoclax)

14d

Clinical Characteristics and Chemosensitivity in Germline TP53 Pathogenic Variant Cases Identified by Cancer Genomic Testing. (PubMed, Cancer Genomics Proteomics)

The present results suggest that gTP53v carriers identified through CGP represent a broader clinical spectrum than classical LFS, while demonstrating potentially favorable treatment outcomes. These results challenge traditional paradigms and emphasize the need for individualized approaches to patient care, particularly in cases with atypical presentations requiring the careful interpretation of mosaicism, de novo mutations, and clonal hematopoiesis.

14 days ago

Retrospective data • Journal

TP53 (Tumor protein P53)

TP53 wild-type

16d

PTEN loss drives p53 LOH and immune evasion in a novel urothelial organoid model harboring p53 missense mutations. (PubMed, Oncogene)

The absence of wild-type Trp53 was associated with upregulation of proliferative signaling, and the presence of a mutant Trp53 allele was associated with immune-excluded microenvironment. This study highlights the functional significance of p53 mutant LOH in bladder carcinogenesis conferring several hallmarks of cancer such as sustaining proliferative signaling and avoiding immune destruction, thus provides a novel immunocompetent mouse model of urothelial carcinoma harboring p53 mutations as a novel tool for cancer immunology research.

16 days ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • KRT5 (Keratin 5)

TP53 mutation • TP53 wild-type

19d

The G-quadruplex experimental drug QN-302 impairs liposarcoma cell growth by inhibiting MDM2 expression and restoring p53 levels. (PubMed, Nucleic Acids Res)

In patient-derived xenograft mouse models, QN-302 treatment reduced tumour volume distribution and was well tolerated. We have identified a novel and effective therapeutic strategy to reduce MDM2 expression and promote p53 reactivation in tumours harbouring wild-type TP53, such as WD/DDLPSs.

19 days ago

Journal

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)

TP53 wild-type

QN-302

19d

A window-of-opportunity trial reveals mechanisms of response and resistance to navtemadlin in patients with recurrent glioblastoma. (PubMed, Sci Transl Med)

We also observed up-regulation of oligodendrocyte differentiation genes with navtemadlin treatment and enrichment of oligodendrocyte transcription factor 2 (OLIG2)-positive cells at relapse, suggesting an unexplored mechanism of navtemadlin tolerance in GBM. Overall, these results indicated that clinically achievable doses of navtemadlin exert pharmacodynamic effects on GBM and suggest that combined treatment with temozolomide may be a route to more durable survival benefits.

19 days ago

Clinical • Journal

TP53 (Tumor protein P53) • OLIG2 (Oligodendrocyte Transcription Factor 2)

TP53 mutation • TP53 wild-type

temozolomide • navtemadlin (KRT-232)

19d

Robust p53 phenotypes and prospective downstream targets in telomerase-immortalized human cells. (PubMed, Oncotarget)

hTERT-RPE1 expressed a p53-responsive transcriptome that was highly representative of diverse experimental systems. We discovered several novel downstream p53 targets of potential clinical relevance including ALDH3A1, which is involved in the detoxification of aldehydes and the metabolism of reactive oxygen species, and nectin cell adhesion molecule 4 (NECTIN4) which encodes a secreted surface protein that is overexpressed in many tumors.

19 days ago

Journal

TP53 (Tumor protein P53) • TERT (Telomerase Reverse Transcriptase) • NECTIN4 (Nectin Cell Adhesion Molecule 4) • DLD (Dihydrolipoamide Dehydrogenase) • ALDH3A1 (Aldehyde Dehydrogenase 3 Family Member A1)

TP53 mutation • TP53 wild-type

20d

A Study to Determine How BI 907828 (Brigimadlin) is Taken up in the Tumor (Phase 0) and to Determine the Highest Dose of BI 907828 (Brigimadlin) That Could be Tolerated (Phase 1a) in Combination With Radiation Therapy in People With a Brain Tumor Called Glioblastoma (clinicaltrials.gov)

P1, N=24, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Dec 2026 --> Aug 2025 | Trial primary completion date: Nov 2026 --> Aug 2025

20 days ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53)

TP53 wild-type • IDH wild-type

brigimadlin (BI 907828)

21d

Combined inhibition of ribonucleotide reductase and WEE1 induces synergistic anticancer activity in Ewing's sarcoma cells. (PubMed, BMC Cancer)

Our findings show that combined inhibition of RNR and WEE1 was effective against Ewing's sarcoma in vitro. They thus provide a rationale for the evaluation of the potential of combined targeting of RNR and WEE1 in Ewing's sarcoma in vivo.

21 days ago

Journal • PARP Biomarker

CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • CASP7 (Caspase 7)

TP53 mutation • TP53 wild-type

Lynparza (olaparib) • adavosertib (AZD1775) • veliparib (ABT-888) • azenosertib (ZN-c3) • Triapine (3-AP)

23d

A Mutual Interaction Between GSTP1 and p53 Improves the Drug Resistance and Malignant Biology of Pancreatic Cancer. (PubMed, Cancer Sci)

Additionally, GSTP1 promoted the translocation of wtp53 into the nucleus but not mtp53. These results suggest that the positive feedback regulation of GSTP1 and wtp53 plays a significant role in cell proliferation, drug resistance, cell invasion and metastasis in PC.

23 days ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • GSTP1 (Glutathione S-transferase pi 1) • BAX (BCL2-associated X protein) • MMP9 (Matrix metallopeptidase 9) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • TJP1 (Tight Junction Protein 1)

TP53 mutation • TP53 wild-type

25d

Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small Molecule Reactivator. (PubMed, Cancer Discov)

These compounds demonstrate potent anti-tumor activity in preclinical models as single agents and in combination with immunotherapy. Currently, rezatapopt is being evaluated in a registrational Phase 2 clinical trial for patients with advanced solid tumors harboring the TP53 Y220C mutation.

25 days ago

Journal • IO biomarker

TP53 (Tumor protein P53)

TP53 mutation • TP53 wild-type • TP53 Y220C

rezatapopt (PC14586)

25d

The G-quadruplex experimental drug QN-302 impairs liposarcoma cell growth by inhibiting MDM2 expression and restoring p53 levels. (PubMed, Nucleic Acids Res)

25 days ago

Journal

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)

TP53 wild-type

QN-302

25d

Comparative In Silico and In Vitro Studies of Novel Zinc/Tin Metal Coordinates Bearing BRCA-1 Mimetics on Wtp53 and Mtp53 Proteins. (PubMed, Protein Pept Lett)

As compared to PRIMA-1, the designed compound TSCO5 metal coordinates have shown good in silico and in vitro activity on mutated p53 cell lines and are more potent than the p53 activator PRIMA-1.

25 days ago

Preclinical • Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA (Breast cancer early onset)

TP53 mutation • TP53 wild-type • BRCA mutation

tamoxifen

25d

Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53. (PubMed, Front Pharmacol)

Even these strategies have been met with limited success. Bypassing p53 entirely may be the next avenue in cancer therapeutics to kill tumor cells regardless of p53's mutation pattern.

25 days ago

Review • Journal

TP53 (Tumor protein P53)

TP53 mutation • TP53 wild-type

26d

Pharmacological Inhibition of MDM2 Induces Apoptosis in p53-Mutated Triple-Negative Breast Cancer. (PubMed, Int J Mol Sci)

We here selected the clinical-stage MDM2 inhibitors Idasanutlin and Milademetan and investigated their anti-tumoral effects in TNBC. This effect was observed despite an inactivating p53 mutation and was apparently independent of p53 expression. Our data suggest that MDM2 is a promising target in TNBC and clinical-stage MDM2 inhibitors should be further evaluated for their potential therapeutic application.

26 days ago

Journal

CASP3 (Caspase 3) • CASP7 (Caspase 7)

TP53 mutation • TP53 wild-type

milademetan (RAIN-32) • idasanutlin (RG7388)

26d

The prognostic value of p53 and Ki-67 expression status in penile cancer: a systematic review and meta-analysis. (PubMed, Pathology)

Evidence regarding Ki-67 status was sparse, but the pooled estimate indicated that penile cancers with high Ki-67 expression may have a slightly worse CSS than those with low Ki-67 expression. These findings may inform clinicians when planning the best management and follow-up strategy for penile cancer patients.

26 days ago

Retrospective data • Review • Journal

TP53 (Tumor protein P53)

TP53 mutation • TP53 wild-type

28d

Case report: Chemotherapy plus sintilimab for the treatment of gastroesophageal junction hepatoid adenocarcinoma with liver metastasis: a case study with literature review. (PubMed, Front Immunol)

The patient achieved a major pathological response (MPR) and remains in a progression-free stage. Sintilimab-based chemotherapy has proven efficacy in achieving a MPR and maintaining a progression-free state for a patient with GEJ HAC that has metastasized to the liver.

28 days ago

Review • Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • JAK2 (Janus kinase 2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MUC1 (Mucin 1) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • AFP (Alpha-fetoprotein) • GPC3 (Glypican 3) • MME (Membrane Metalloendopeptidase) • KRT19 (Keratin 19) • DPYD (Dihydropyrimidine Dehydrogenase) • CA 19-9 (Cancer antigen 19-9)

EGFR mutation • PIK3CA mutation • TP53 wild-type

Tyvyt (sintilimab)

28d

ALLIANCE-ABTC-1604: Testing the Ability of AMG 232 (KRT 232) to Get Into the Tumor in Patients With Brain Cancer (clinicaltrials.gov)

P1, N=32, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting | N=86 --> 32 | Trial completion date: Dec 2024 --> Feb 2026

28 days ago

Enrollment closed • Enrollment change • Trial completion date

TP53 (Tumor protein P53) • MGMT (6-O-methylguanine-DNA methyltransferase)

TP53 wild-type

navtemadlin (KRT-232)

Breaking through with ultrasound: TP53-driven efficacy of calcium sonoporation in pediatric rhabdomyosarcoma cells. (PubMed, Biomed Pharmacother)

The research laid the groundwork for future studies to optimise sonoporation parameters and explore its integration with existing cancer treatments. The insights gained from this study pave the way for developing more personalized cancer treatment strategies, particularly for tumors influenced by specific genetic contexts, such as TP53 mutations.

1 month ago

Journal

TP53 (Tumor protein P53)

TP53 mutation • TP53 wild-type

Impact of developmental state, p53 status, and interferon signaling on glioblastoma cell response to radiation and temozolomide treatment. (PubMed, PLoS One)

We observed that activation of NF-κB was positively correlated with the levels of O-6-methylguanine-DNA methyltransferase (MGMT) protein, a direct DNA repair enzyme leading to TMZ resistance, regardless of MGMT promoter methylation status, further supporting the clinical potential for inhibition of NF-kB signaling in GBM treatment. Our integrative analysis of the impact of GBM cell developmental states, in the context of genomic and molecular diversity of patient-derived models, provides valuable insights for pre-clinical studies aimed at optimizing treatment strategies.

1 month ago

Journal

TP53 (Tumor protein P53) • MGMT (6-O-methylguanine-DNA methyltransferase)

TP53 mutation • TP53 wild-type • MGMT promoter methylation

temozolomide

A Study in People With Advanced Cancer to Test Whether the Amount of BI 907828 in the Blood is Influenced by Taking an OATP Inhibitor or a CYP3 Inhibitor (clinicaltrials.gov)

P1, N=34, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Feb 2025 --> Jun 2025

1 month ago

Trial completion date

TP53 (Tumor protein P53)

TP53 wild-type

brigimadlin (BI 907828) • itraconazole • rifampicin

MDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis. (PubMed, NPJ Precis Oncol)

This case suggests that MDM2 inhibitors are associated with TP53 clonal hematopoiesis, which may confer a risk of subsequent myeloid malignancy. As multiple MDM2 inhibitor trials are ongoing, our findings underscore the need for further investigation into the potential long-term deleterious effects of these inhibitors in the hematopoietic stem and progenitor compartment.

1 month ago

Journal

MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • TP53 wild-type

TP53 Alterations Associate with Poor Response to Lenvatinib in Patients with Advanced Thyroid Cancer. (PubMed, J Clin Endocrinol Metab)

We show for the first time in advanced TC that the presence of TP53 alterations is a predictor of poor response to LEN treatment and associates to worse PFS and OS rates. The evaluation of TP53 mutations/p53 expression might be included into the patient/tumor characterization to be done before starting an MKI treatment.

1 month ago

Journal

TP53 (Tumor protein P53)

TP53 mutation • TP53 wild-type

Lenvima (lenvatinib)

The key vulnerabilities and therapeutic opportunities in the USP7-p53/MDM2 axis in cancer. (PubMed, Biochim Biophys Acta Mol Cell Res)

However, there is still much to be done in this area. If the hypothesis is correct, USP7 may be a potent target in cancers containing both Wt-p53 and Mut-p53.

1 month ago

Review • Journal

USP7 (Ubiquitin Specific Peptidase 7)

TP53 mutation • TP53 wild-type

Avo In R/R And Previously Untreated MCL (clinicaltrials.gov)

P1/2, N=53, Recruiting, Austin I Kim | Trial primary completion date: Dec 2024 --> Dec 2025

1 month ago

Trial primary completion date

TP53 (Tumor protein P53)

TP53 wild-type

clonoSEQ

Venclexta (venetoclax) • Gazyva (obinutuzumab) • Calquence (acalabrutinib)

Prognosis of TP53 and Its Concomitant EGFR Mutation in Lung Cancer Especially Non-Small Cell Lung Cancer. (PubMed, Asian Pac J Cancer Prev)

Studies have shown that TP53 mutation is unlikely to derive clinical benefit in LC patients and shows poorer prognosis when compared to TP53 wild type and EGFR mutated patients show improved recovery due to availability of the Kinase Inhibitor (KI) treatment. In this study we have observed and concluded that TP53-EGFR co-mutated group also shows promising prognosis for the application of KI treatment. A further large cohort study will establish this clinical observation and enlighten more therapeutically relevant information.

1 month ago

Retrospective data • Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53)

TP53 mutation • EGFR mutation • TP53 wild-type

TP53 Mutations in Myeloproliferative Neoplasms: Context-Dependent Evaluation of Prognostic Relevance. (PubMed, Am J Hematol)

Multihit TP53MUT was also associated with inferior survival following allogeneic stem cell transplant (ASCT): median 9 months versus "not reached" in patients with (N = 9) versus without (N = 8) multihit TP53MUT (p < 0.01). The presence of multihit or non-multihit TP53MUT in MPN-BP/AP or multihit TP53MUT in MF-CP is associated with exceptionally poor prognosis and justifies inclusion into the ICC category of "myeloid neoplasms with mutated TP53." By contrast, detection of non-multihit TP53MUT, by itself, might not endanger short-term survival in MF-CP, PV, or ET.

1 month ago

Journal

TP53 (Tumor protein P53) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

TP53 mutation • TP53 wild-type • ASXL1 mutation • SRSF2 mutation

Utilizing TP53 hotspot mutations as effective predictors of gemcitabine treatment outcome in non-small-cell lung cancer. (PubMed, Cell Death Discov)

This potential effectiveness might arise from its ability to disrupt DNA damage repair processes, leading to G2/M phase cell cycle arrest or an augmentation of mitotic abnormalities, eventually cause cell death. As a result, when planning treatment strategies for NSCLC patients possessing TP53 hotspot mutations, gemcitabine should be considered to incorporate into the indication.

1 month ago

Journal

TP53 (Tumor protein P53)

TP53 mutation • TP53 wild-type

gemcitabine

Verruciform Acanthotic Vulvar Intraepithelial Neoplasia Harbors Recurrent Genomic Alterations Found in HPV-independent Squamous Cell Carcinoma. (PubMed, Int J Gynecol Pathol)

vaVIN can occur with concurrent or subsequent carcinoma, sometimes with fatal outcomes. These findings support the concept of vaVIN as a neoplastic process within the family of HPV-independent vulvar neoplasia.

1 month ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • TSC2 (TSC complex subunit 2) • NOTCH2 (Notch 2) • FAT1 (FAT atypical cadherin 1) • ARID2 (AT-Rich Interaction Domain 2)

TP53 mutation • TP53 wild-type

Meta-analysis of the ability of mutational profiles on the cancer genome atlas to predict prognosis in endometrial carcinoma. (PubMed, Int J Gynaecol Obstet)

The four mutational profiles for patients with endometrial carcinoma in the Cancer Genome Atlas for Endometrial Cancer are associated with worse to better survival in the trend: p53abn < MMRd < POLEmut ≈ p53wt. Mutational profiling may be useful for stratifying endometrial carcinoma patients by survival risk, which in turn may improve their management.

1 month ago

Retrospective data • Review • Journal

TP53 (Tumor protein P53)

TP53 mutation • TP53 wild-type

TP53 Wild-type, HPV-independent Anal Growth/(intra)Epithelial Lesion (ANGEL): a Potential Precursor of Anal Squamous Cell Carcinoma. (PubMed, Mod Pathol)

Invasive SCC was concurrently present in 3/5 cases. In summary, verrucous and acanthotic HPV-independent TP53 wild-type squamous proliferations of the anal and perianal region, referred herein as ANGELs (anal growth/(intra)epithelial lesions), are pre-malignant lesions that have the potential to become invasive, as most of our cases demonstrated synchronous SCC.

1 month ago

Journal

TP53 (Tumor protein P53)

TP53 mutation • TP53 wild-type

iNOS-Produced Nitric Oxide from Cancer Cells as an Intermediate of Stemness Regulation by PARP-1 in Colorectal Cancer. (PubMed, Biomolecules)

Treatment with 1400 W, a selective inhibitor of iNOS, or gene silencing of the gene counteracted the effects of PARP-1 in both p53 wild-type and p53 mutated cells. Given that the development of resistance has been demonstrated after treatment with PARP-1 inhibitors, iNOS could be considered a new therapeutic target in CRC, although only in patients with wild-type p53 tumors.

1 month ago

Journal • PARP Biomarker

PARP1 (Poly(ADP-Ribose) Polymerase 1)

TP53 mutation • TP53 wild-type

Targeting the MDM2-p53 Interaction with Siremadlin: A Promising Therapeutic Strategy for Treating TP53 Wild-Type Chronic Lymphocytic Leukemia. (PubMed, Cancers (Basel))

The results underline the importance of TP53 status in predicting treatment efficacy and highlight the potential of HDM201 as a valuable addition to explore in CLL therapy. Future research should focus on identifying additional biomarkers of response and exploring the optimal way to include HDM201 in combination therapies to improve treatment outcomes in CLL.

1 month ago

Journal

TP53 (Tumor protein P53)

TP53 mutation • TP53 wild-type

siremadlin (HDM201)