News - TP53 amplification

GLI1, CDK4, and MDM2 Co-Amplification Gastric Plexiform Fibromyxoma: A Case Report and Literature Review. (PubMed, Genes Chromosomes Cancer)

No recurrence was observed during the follow-up period of 8 months. This study aims to improve our understanding of PF by analyzing the clinicopathological characteristics of this case, including immunohistochemical (IHC) and genetic examination, and reviewing relevant literature.

4 days ago

Review • Journal

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • CD34 (CD34 molecule) • GLI1 (GLI Family Zinc Finger 1) • MALAT1 (Metastasis associated lung adenocarcinoma transcript 1) • STAT6 (Signal transducer and activator of transcription 6)

TP53 mutation • CDK4 amplification • TP53 amplification • CDK4 mutation

23d

Hepatitis B Virus X Protein Induces Reactive Oxygen Species Generation via Activation of p53 in Human Hepatoma Cells. (PubMed, Biomolecules)

Additionally, HBx variants with Ser-101 increased p53 and ROS levels, whereas variants with Pro-101 did not. These dual mechanisms of HBx-induced ROS generation are likely significant in the pathogenesis of HBV and may contribute to liver diseases, including hepatocellular carcinoma.

23 days ago

Journal

CAT (Catalase)

TP53 expression • TP53 amplification

23d

Re-evaluation of the concept of basaloid follicular hamartoma associated with naevoid basal cell carcinoma syndrome: a morphological, immunohistochemical and molecular study. (PubMed, Pathology)

Targeted next-generation sequencing suggested that MYCN and GLI2/3 amplifications and TP53 mutations might be involved in progression of these follicular tumours to BCC. Our study confirms the high prevalence of BFH, representing up to 24% of skin tumours in NBCCS and potentially being BCC precursors.

23 days ago

Journal

TP53 (Tumor protein P53) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • GLI2 (GLI Family Zinc Finger 2)

TP53 mutation • TP53 amplification

28d

This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors) (clinicaltrials.gov)

P1, N=267, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

28 days ago

Enrollment closed • Metastases

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

TP53 wild-type • MDM2 amplification • TP53 amplification

brigimadlin (BI 907828)

A case of esophageal squamous cell carcinoma with epidermization showing a unique morphology. (PubMed, Clin J Gastroenterol)

Cancer genome analysis revealed mutations in TP53 as well as amplification of MYC, FGFR1, chromosome 7, and chromosome 20q. This case suggests that epidermoid metaplasia caused by chronic irritation from an esophageal stricture may have been exacerbated by the dilation procedure.

1 month ago

Journal

TP53 (Tumor protein P53) • FGFR1 (Fibroblast growth factor receptor 1)

TP53 mutation • TP53 amplification

2ms

Molecular Analysis of High-Grade Serous Ovarian Carcinoma Exhibiting Low-Grade Serous Carcinoma and Serous Borderline Tumor. (PubMed, Curr Issues Mol Biol)

After surgery, TC (Paclitaxel + Carbopratin) + bevacizumab therapy was administered as adjuvant chemotherapy followed by bevacizumab as maintenance therapy. DNA methylation analysis did not show differentially methylated regions. This case suggests that SBT and LGSC may transform into HGSC via p53 dysfunction due to MDM2 amplification.

2 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • TP53 wild-type • KRAS G12V • MDM2 amplification • KRAS G12 • TP53 amplification

Avastin (bevacizumab) • paclitaxel

2ms

CDK4 is co-amplified with either TP53 promoter gene fusions or MDM2 through distinct mechanisms in osteosarcoma. (PubMed, NPJ Genom Med)

Additionally, we observed recurring promoter swapping events involving the regulatory regions of the FRS2, PLEKHA5, and TP53 genes. These events resulted in ectopic expression of partner genes, with the ELF1 gene being upregulated by the FRS2 and TP53 promoter regions in two distinct cases.

2 months ago

Journal

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • FRS2 (Fibroblast Growth Factor Receptor Substrate 2) • ELF1 (E74 Like ETS Transcription Factor 1)

MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • TP53 amplification

2ms

Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder (clinicaltrials.gov)

P2, N=103, Recruiting, Boehringer Ingelheim | N=155 --> 103

2 months ago

Enrollment change • Metastases

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

TP53 wild-type • MDM2 amplification • TP53 amplification

brigimadlin (BI 907828)

2ms

TP53 and EGFR amplification are negative predictors of overall survival in patients diagnosed with non-small cell lung cancer with brain metastases. (PubMed, Heliyon)

Gene signatures, such as TP53 or EGFR amplification, were associated with worse survival in patients diagnosed with NSCLC-BM. These valuable findings may shed light on new strategies for the prognostic assessment of specific patient groups.

2 months ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • LRP1B (LDL Receptor Related Protein 1B) • RNF43 (Ring Finger Protein 43)

TP53 mutation • EGFR amplification • RNF43 mutation • TP53 amplification

2ms

Clinicopathological and molecular characteristics of pediatric gliomas: analysis of 111 cases (PubMed, Zhonghua Bing Li Xue Za Zhi)

There are significant differences in clinical manifestations, pathological characteristics, molecular variations, and prognosis between the pDLGG, CAG and pDHGG groups. The integrated diagnosis combining histology and molecular features is of great importance for the accurate diagnosis and treatment of pediatric gliomas.

2 months ago

Journal

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler) • KIAA1549 • H3-3A (H3.3 Histone A)

TP53 mutation • BRAF V600E • BRAF V600 • KIAA1549-BRAF fusion • BRAF fusion • TP53 amplification

6ms

A Study in Patients With Different Types of Advanced Cancer (Solid Tumors) to Test Different Doses of BI 907828 in Combination With BI 754091 (Ezabenlimab) and BI 754111 or BI 907828 in Combination With BI 754091 (Ezabenlimab) (clinicaltrials.gov)

P1, N=119, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

6 months ago

Enrollment closed • Combination therapy • Metastases

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

TP53 mutation • TP53 wild-type • TP53 amplification

brigimadlin (BI 907828) • ezabenlimab (BI 754091) • miptenalimab (BI 754111)

7ms

ALRN-6924 and Paclitaxel in Treating Patients With Advanced, Metastatic, or Unresectable Solid Tumors (clinicaltrials.gov)

P1, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Phase classification: P1b --> P1

7 months ago

Phase classification • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • MDM4 (The mouse double minute 4) • GDF15 (Growth differentiation factor 15) • CASP3 (Caspase 3) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)

ER positive • HER-2 negative • TP53 wild-type • MDM4 amplification • MDM2 mutation • TP53 amplification

paclitaxel • ALRN-6924

8ms

Next-generation sequencing reveals genetic heterogeneity and resistance mechanisms in patients with EGFR-mutated non-small cell lung cancer treated with afatinib. (PubMed, ERJ Open Res)

EGFR p.T790M is not only the major resistance mechanism to afatinib but also related to favourable survival outcomes. MET amplification and TP53 mutations were associated with poorer overall survival.

8 months ago

Journal • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • MUC16 (Mucin 16, Cell Surface Associated) • FAT1 (FAT atypical cadherin 1) • USH2A (Usherin) • RECQL4( RecQ Like Helicase 4)

TP53 mutation • EGFR mutation • HER-2 amplification • MET amplification • EGFR T790M • KRAS amplification • TP53 amplification

Gilotrif (afatinib)

8ms

P1, N=140, Recruiting, Boehringer Ingelheim | Phase classification: P1a/1b --> P1

8 months ago

Phase classification • Combination therapy • Metastases

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

TP53 mutation • TP53 wild-type • TP53 amplification

brigimadlin (BI 907828) • ezabenlimab (BI 754091) • miptenalimab (BI 754111)

9ms

Cytomorphology of Non-Small Cell Lung Carcinoma with MET Exon 14 Skipping Mutations (USCAP 2024)

One patient received Capmatinib and one patient Pembrolizumab. This study showed that NSCLC with METex14 are poorly differenciated tumors with necrotic background,multinucleation,atypical mitoses,and pleomorphic/sarcomatoid features. Larger studies are needed to confirm our preliminary findings. Routine NGS testing on cytological specimens is feasible and essential for METex14 testing and select patients with advanced lung NSCLC for targeted therapies.

9 months ago

PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase) • NKX2-1 (NK2 Homeobox 1)

TP53 mutation • HER-2 amplification • HER-2 mutation • MET amplification • MET exon 14 mutation • MET mutation • TP53 amplification

Oncomine Focus Assay

Keytruda (pembrolizumab) • Tabrecta (capmatinib)

9ms

Genomic Variability Within Intrinsic Subtypes of Advanced Breast Cancer (USCAP 2024)

There is a great genomic variability in each intrinsic subtype of advanced BC, with apparently no genomic pattern correlating with each phenotype. Although a transcriptomic test (Prosigna) can help in the classification of the tumors, NGS sequencing with an extended panel allows identifying genetic variants that might benefit the patient with a targeted therapy i a significant percentage of cases.

9 months ago

BRCA Biomarker • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SF3B1 (Splicing Factor 3b Subunit 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3)

HER-2 negative • PTEN mutation • MYC amplification • CCND1 amplification • AKT1 mutation • TP53 amplification

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

10ms

Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets. (PubMed, Int J Mol Sci)

Recent evidence also shows that inhibition of Cyclin-dependent kinases (CDKs), such as CDK4/6, CDK2, CDK8/19 and CDK12/13 can contribute to RS through disruption of DNA repair and replication control. Here, we review the main causes of RS in cancers as well as main therapeutic targets-ATR, CHK1, PARP and their inhibitors.

10 months ago

Review • Journal • PARP Biomarker

RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • CDK2 (Cyclin-dependent kinase 2) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)

TP53 mutation • ATM mutation • CCNE1 amplification • RB1 mutation • TP53 amplification

10ms

Establishment and characterization of a novel hypopharyngeal squamous cell carcinoma cell line CZH1 with genetic abnormalities. (PubMed, Hum Cell)

Whole-exome sequencing analysis revealed that CZH1 cells had typical genomic features of HNSCC, including mutations of TP53 and amplifications of multiple transcripts. Therefore, our newly developed CZH1 cell line could serve as an efficient tool for the in vitro investigation of the etiology, pathogenesis, and preclinical treatment of HPSCC.

10 months ago

Preclinical • Journal

TP53 (Tumor protein P53)

TP53 mutation • TP53 amplification

10ms

As our understanding of biology evolves, there has been increased morphologic recognition and characterization of tumor phenotypes that are present in this advanced post-treatment setting. New and promising biomarkers (delta-like ligand 3 and others) have been discovered, which opens up novel therapeutic avenues including immunotherapy and antibody-drug conjugates for this lethal disease with currently limited treatment options.

10 months ago

Journal • IO biomarker

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • AURKA (Aurora kinase A) • SOX2

EZH2 overexpression • TP53 amplification

10ms

Brightline-2: a phase IIa/IIb trial of brigimadlin (BI 907828) in advanced biliary tract cancer, pancreatic ductal adenocarcinoma or other solid tumors. (PubMed, Future Oncol)

Brigimadlin (BI 907828) is a highly potent MDM2-p53 antagonist that has shown promising activity in preclinical and early-phase clinical studies. This manuscript describes the rationale and design of an ongoing phase IIa/IIb Brightline-2 trial evaluating brigimadlin as second-line treatment for patients with advanced/metastatic BTC, PDAC, lung adenocarcinoma, or bladder cancer.

10 months ago

P2a data • Review • Journal • Metastases

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

TP53 wild-type • MDM2 amplification + TP53 wild-type • TP53 amplification

brigimadlin (BI 907828)

11ms

Symphony in the crowd: Key genetic alterations in prostate cancer. (PubMed, Cancer Innov)

The most common genetic alterations that give rise to distinct androgen different differentiation states are gene fusion of TMPRSS2 with ETS family genes, deletion, or mutation of tumor suppressor PTEN and TP53 gene, amplification or splicing of AR, altered DNA repair genes. In this review, we describe key genes and genetic changes that have been recognized to contribute to altered prostate environment.

11 months ago

Review • Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • TMPRSS2 (Transmembrane serine protease 2)

TP53 mutation • PTEN mutation • TP53 amplification

12ms

MDM2 amplification is rare in gastric cancer. (PubMed, Virchows Arch)

Our targeted analysis of MDM2 in a well-characterized cohort of GC patients showed that MDM2 amplification is rare, of no specific histological phenotype, and may not be always mutually exclusive with TP53 mutations. Given the low number of cases, currently, no diagnostic or therapeutic recommendation related to MDM2 amplification can be given for GC of Western origin.

12 months ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • FGFR2 mutation • MDM2 amplification • MDM2 mutation • TP53 amplification

12ms

Comprehensive clinico-molecular profile and efficacy of anti-HER2 therapy for HER2-amplified biliary tract cancer. (ASCO-GI 2024)

HER2 amplifications were found in 10% of advanced BTC and did not represent an independent predictive factor for OS. Of clinical significance, patients with HER2-amplified BTC derive a significant benefit from anti-HER2 therapy.

12 months ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53)

TP53 mutation • BRAF mutation • HER-2 amplification • BRAF amplification • TP53 amplification

FoundationOne® CDx • Guardant360® CDx • FoundationOne® Liquid CDx • Tempus xT Assay

12ms

Sarcomas harboring EWSR1::PATZ1 fusions: A Clinicopathologic Study of 17 Cases. (PubMed, Mod Pathol)

We conclude that the morphologic spectrum of EWSR1::PATZ1 is broader than has been previously appreciated. Although more long-term follow-up is needed, the prognosis of these very rare sarcomas may be more favorable than previously reported.

12 months ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • EWSR1 (EWS RNA Binding Protein 1) • SOX10 (SRY-Box 10) • CD99 (CD99 Molecule) • GFAP (Glial Fibrillary Acidic Protein) • MYOD1 (Myogenic Differentiation 1) • PATZ1 (POZ/BTB And AT Hook Containing Zinc Finger 1)

TP53 wild-type • MDM2 amplification • TP53 expression • TP53 amplification

12ms

Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures. (PubMed, Nat Commun)

Single-cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. High-throughput drug screening using both mouse and human tumor cells finally indicated high efficacy of Doxorubicin, Irinotecan, and Etoposide as possible therapy options that children with HGG-MYCN might benefit from.

12 months ago

Preclinical • Journal

TP53 (Tumor protein P53) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)

TP53 mutation • MYCN amplification • TP53 amplification

doxorubicin hydrochloride • etoposide IV • irinotecan

12ms

Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder (clinicaltrials.gov)

P2, N=155, Recruiting, Boehringer Ingelheim | Phase classification: P2a/2b --> P2

12 months ago

Phase classification

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

TP53 wild-type • MDM2 amplification • TP53 amplification

brigimadlin (BI 907828)

1year

This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors) (clinicaltrials.gov)

P1, N=269, Recruiting, Boehringer Ingelheim | Phase classification: P1a/1b --> P1 | N=204 --> 269

1 year ago

Phase classification • Enrollment change • Metastases

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

TP53 wild-type • MDM2 amplification • TP53 amplification

brigimadlin (BI 907828)

1year

Mutant-p53 amplifies Cxcl1 expression from distal enhancers blunting immune checkpoint inhibition efficacy in pancreatic cancer (SITC 2023)

Furthermore, we examined the interplay between p53R172H and NF-kB and found that the p53R172H physically interacts with the NF-kB subunit RelA and facilitates its nuclear translocation. Conclusions Overall, we characterize how a common p53 mutation in PDAC co-opts non-coding regulatory DNA to augment the expression of selective chemokine genes and establishes an immunosuppressive TME to shield the therapeutic benefits of ICIs.

1 year ago

Clinical • Late-breaking abstract • Checkpoint inhibition • Tumor mutational burden • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CXCL1 (Chemokine (C-X-C motif) ligand 1)

TP53 mutation • KRAS mutation • KRAS G12D • TMB-L • TP53 deletion • KRAS G12 • TP53 expression • TP53 R172H • TP53 amplification

1year

MANTRA-2: Milademetan in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)

P2, N=40, Terminated, Rain Oncology Inc | N=65 --> 40 | Trial completion date: Aug 2024 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2024 --> Oct 2023; Sponsor Decision

1 year ago

Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Pan tumor • Metastases

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

TP53 mutation • TP53 wild-type • MDM2 amplification • TP53 amplification

milademetan (RAIN-32)

1year

ALRN-6924 and Paclitaxel in Treating Patients With Advanced, Metastatic, or Unresectable Solid Tumors (clinicaltrials.gov)

P1b, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2023 --> Apr 2025 | Trial primary completion date: Jul 2023 --> Apr 2025

1 year ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • MDM4 (The mouse double minute 4)

ER positive • HER-2 negative • TP53 wild-type • MDM4 amplification • TP53 amplification

paclitaxel • ALRN-6924

1year

Comprehensive genomic analysis in Mantle Cell Lymphoma identifies risk factors and predicts patients’ outcome: results from the EU-MCL network trials (DGHO 2023)

Genomic analysis in circulating MCL cells using the EC-NDC assay provides comprehensive information on genetic alterations in MCL leading to better disease characterization and risk assessment. Implementing routine genomic profiling in MCL may be useful in the era of precision medicine and individualized patient management

1 year ago

Clinical • IO biomarker • Genomic analysis • Omic analysis

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • KMT2D (Lysine Methyltransferase 2D) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • TNFAIP3 (TNF Alpha Induced Protein 3) • CD79A (CD79a Molecule) • BCL3 (BCL3 Transcription Coactivator) • NFKBIE (NFKB Inhibitor Epsilon)

TP53 mutation • ATM mutation • NOTCH1 mutation • Chr t(11;14) • CDKN2A deletion • CDKN2A mutation • RB1 deletion • TP53 amplification

1year

Epithelial-to-mesenchymal transition status correlated with ultrastructural features, and TP53 mutation in patient-derived oral cancer cell lines. (PubMed, Mol Biol Rep)

Cellular migratory properties are associated with cellular ultrastructure, epithelial-to-mesenchymal transition status and the status of TP53 mutation in the genome.

1 year ago

Preclinical • Journal

TP53 (Tumor protein P53) • CDH1 (Cadherin 1) • VIM (Vimentin) • TWIST1 (Twist Family BHLH Transcription Factor 1) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)

TP53 mutation • TP53 wild-type • CDH1 expression • VIM expression • TP53 amplification • ZEB1 expression • TP53 R196*

1year

Teclistamab Is Safe and Effective In Relapse Refractory Multiple Myeloma Patients with End Stage Renal Disease: A Case Series (IMW 2023)

Prior to treatment, his lambda light chain was 4547.5 mg/L and an IgG 1930 mg/dL with the following high risk features: 8 prior lines of therapy including belantamab; high risk genomics (loss of TP53, amplification 1q, 13q deletion); extramedullary disease. Severe manufacturing shortages of BCMA directed CAR-T therapy (idecel and ciltacel) are daunting with no clear solution in sight. Thus an efficacious bispecific antibody targeting BCMA is sorely needed. Cytopenias and CKD/ESRD would have made both of our patients above ineligible for the MajesTEC-1 trial.

1 year ago

Clinical

TP53 (Tumor protein P53)

TP53 amplification

Blenrep (belantamab mafodotin-blmf) • Tecvayli (teclistamab-cqyv)

1year

Genomic and tumour microenvironmental biomarkers of immune checkpoint inhibitor response in advanced Taiwanese melanoma. (PubMed, Clin Transl Immunology)

Genetic alterations in the p53 pathway may be critical in Asian patients with melanoma undergoing ICI treatment. Further investigation is required to explore this mechanism and validate these findings.

1 year ago

Checkpoint inhibition • Journal • Tumor mutational burden • IO biomarker • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • MDM2 (E3 ubiquitin protein ligase) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)

TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • KIT mutation • NF1 mutation • TP53 amplification

ACTOnco

over1year

Clinical activity and exploratory resistance mechanism of milademetan, an MDM2 inhibitor, in intimal sarcoma with MDM2 amplification: an open-label phase 1b/2 study. (PubMed, Cancer Discov)

Acquired TP53 mutations were detected in sequential liquid biopsies as a novel exploratory resistance mechanism to milademetan. These results suggest that milademetan could be a potential therapeutic strategy for intimal sarcoma.

over 1 year ago

P1/2 data • Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase) • TWIST1 (Twist Family BHLH Transcription Factor 1)

TP53 mutation • TP53 wild-type • MDM2 amplification • CDKN2A negative • TP53 amplification

milademetan (RAIN-32)

over1year

MANTRA-2: Milademetan in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)

P2, N=65, Active, not recruiting, Rain Oncology Inc | Recruiting --> Active, not recruiting

over 1 year ago

Enrollment closed • Pan tumor • Metastases

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

TP53 mutation • TP53 wild-type • MDM2 amplification • TP53 amplification

milademetan (RAIN-32)

over1year

Importance of the resected lung tumor specimen in patients with locally advanced and metastatic non-small cell lung cancer undergoing prior targeted therapy (ESMO 2023)

Furthermore, patients with T790M mutation showed a trend towards improved PFS (P=0.052). Conclusions Lung surgery following targeted therapies is safe and can be used to predict the prognosis of patients with initially unresectable NSCLC.

over 1 year ago

Clinical • Metastases

ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)

TP53 mutation • EGFR mutation • MET amplification • EGFR T790M • MET mutation • TP53 amplification

over1year

Autopsy and Next Generation Sequencing Report of First-Line Treatment with Osimertinib for EGFR-Mutated Squamous Cell Carcinoma of the Lung (IASLC-WCLC 2023)

The current case report shows that next-generation sequencing can explain why osimertinib is ineffective in EGFR-mutated SCC. The therapeutic strategy for patients with EGFR mutant-positive SCC should include an analysis of coexisting genetic abnormalities by next-generation sequencing. Therapy with EGFR tyrosine kinase inhibitor might be recommended if no additional gene associated with resistance to tyrosine kinase inhibitor is detected.

over 1 year ago

Clinical • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDK6 (Cyclin-dependent kinase 6)

TP53 mutation • KRAS mutation • EGFR mutation • EGFR exon 19 deletion • EGFR positive • KRAS amplification • TP53 amplification

Tagrisso (osimertinib)

over1year

Combination of Osimertinib plus Capmatinib in a Patient with EGFR-mutant, T790M positive and MET amplification: A Case Report (IASLC-WCLC 2023)

Patient received erlotinib 150 mg daily as frontline treatment in December 2018. We present the case of a patient with advanced stage NSCLC, with EGFR mutation, Secondary T790M positive and MET amplification, received osimertinib and capmatinib as third-line treatment. The efficacy was different from previous report (1), using both combination in EGFR mutation, T790M negative, MET-amplified patient, emphasizing the marginal effect in this subgroup.

over 1 year ago

Clinical • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

TP53 mutation • EGFR mutation • EGFR L858R • MET amplification • EGFR T790M • EGFR exon 20 insertion • MET mutation • EGFR exon 20 mutation • EGFR T790M negative • EGFR L858R + EGFR exon 21 deletion • TP53 amplification

Tagrisso (osimertinib) • erlotinib • Tabrecta (capmatinib)

over1year

Aumolertinib Plus Anlotinib in Advanced NSCLC with Brain Metastasis: A Single-arm, Phase II Study (IASLC-WCLC 2023)

In addition, EGFR-TKIs combined with bevacizumab can further improve the efficacy, as reported in study JO25567 and NEJ026. Aumolertinib plus anlotinib showed preliminary efficacy as first-line therapy in EGFR-mutant NSCLC patients with brain metastases. The initial subgroup results may demonstrated superior activity of aumolertinib plus anlotinib in patients with multiple intracranial metastases or EGFR 19Del positive. And although with comutations, NSCLC patients with brain metastasis can still benefit from aumolertinib plus anlotinib.

over 1 year ago

P2 data • Metastases

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • CCND1 (Cyclin D1)

TP53 mutation • EGFR mutation • PIK3CA mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR amplification • PIK3CA amplification • CCND1 amplification • EGFR positive • TP53 amplification

Avastin (bevacizumab) • Focus V (anlotinib) • Ameile (aumolertinib)

over1year

Comprehensive Cancer Genomic Profiling In Matched Primary Tumor And Brain Metastasis Samples Of Ovarian Cancer Patients: A Single-Institution Case Series. (ESGO 2023)

A phylogenetic analysis is still ongoing at our center. This more comprehensive evaluation may pave the way toward a more precise understanding of the genetics underneath the development of BM, potentially revealing novel molecular targets and leading to prospective future studies and more personalized treatment.

over 1 year ago

Clinical • Tumor mutational burden • BRCA Biomarker

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • KIF5B (Kinesin Family Member 5B) • CCNE1 (Cyclin E1)

TP53 mutation • PIK3CA mutation • PTEN mutation • RET mutation • TP53 amplification

TruSight Oncology 500 Assay