News - PTEN deletion - LARVOL VERI

Genomic Profiling in Glioma Patients to Explore Clinically Relevant Markers. (PubMed, Int J Mol Sci)

In IDH-wildtype glioblastoma patients, a history of other precedent cancer was associated with worse overall survival (OS), while re-operation and bevacizumab therapy increased OS...Nine patients received molecular targeted therapy, and the results were evaluated. The search for molecular changes associated with tumor growth and progression is important for diagnosis and choice of therapy.

5 days ago

Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler)

TP53 mutation • PIK3CA mutation • IDH1 mutation • PTEN deletion • PTEN mutation • TERT mutation • IDH mutation + Chr del(1p) + Chr del(19q)

Avastin (bevacizumab)

Momordica charantia Extract Ameliorates Melanoma Cell Proliferation and Invasion into Mouse Lungs by Suppressing PAX3 Expression. (PubMed, Int J Mol Sci)

Furthermore, it decreased microphthalmia-associated transcription factors and induced the suppression of cyclin-dependent kinase 2, hepatocyte growth factor receptor, B-cell/CLL lymphoma 2, and Ras-related proteins. Our findings suggest that the MC extract suppresses tumor survival genes by regulating PAX3, thereby ameliorating melanoma proliferation and invasion.

5 days ago

Preclinical • Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDK2 (Cyclin-dependent kinase 2) • MITF (Melanocyte Inducing Transcription Factor) • PAX3 (Paired Box 3)

PTEN deletion

10d

Negative response to immunotherapy in dMMR or MSI-H gastric cancer with APC and PTEN mutations: a case report. (PubMed, Front Oncol)

We attempted to elucidate the underlying causes and mechanisms behind this lack of response, and to provide new insights into treatment options for these patients. Mutations of key genes within tumor-related signaling pathways and the infiltration of CD8+T cells in the tumor microenvironment may influence the efficacy of immunotherapy for MSI-H solid tumors.

10 days ago

Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • CD8 (cluster of differentiation 8) • APC (APC Regulator Of WNT Signaling Pathway)

PD-L1 expression • TMB-H • MSI-H/dMMR • PD-L1 overexpression • PTEN deletion • PTEN mutation • APC mutation

13d

Assessing DNA Changes in High Risk Prostate Cancer to Determine Prognosis (clinicaltrials.gov)

P=N/A, N=0, Withdrawn, Dr. Tamim Niazi | N=132 --> 0 | Active, not recruiting --> Withdrawn

13 days ago

Enrollment change • Trial withdrawal

PTEN (Phosphatase and tensin homolog) • ERG (ETS Transcription Factor ERG) • TMPRSS2 (Transmembrane serine protease 2)

PTEN deletion • TMPRSS2-ERG fusion

26d

Novel Fibroblast Growth Factor Receptor 3-Fatty Acid Synthase Gene Fusion in Recurrent Epithelioid Glioblastoma Linked to Aggressive Clinical Progression. (PubMed, Curr Oncol)

Postoperative treatment included radiotherapy and temozolomide...The recurrence was managed with regorafenib and bevacizumab, though complications like hand-foot syndrome and radiation necrosis arose...The novel FGFR3-FASN fusion suggests potential implications for GBM recurrence and lipid metabolism. Further studies are warranted to explore FGFR3-FASN's role in GBM and its therapeutic targeting.

26 days ago

Journal

PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FASN (Fatty acid synthase)

IDH2 mutation • PTEN deletion • PTEN mutation • CDKN2A deletion • CDKN2A mutation • TERT mutation • TERT promoter mutation

Avastin (bevacizumab) • temozolomide • Stivarga (regorafenib)

JAK/STAT signaling maintains an intermediate cell population during prostate basal cell fate determination. (PubMed, Nat Genet)

In humans, h-Basal-B cells were more prevalent in benign prostate hyperplasia. This study reveals the identities of intermediate Basal-B cells and underscores the role of JAK/STAT signaling in prostate cell fate determination.

1 month ago

Journal

PTEN (Phosphatase and tensin homolog) • NKX3-1 (NK3 homeobox 1)

PTEN deletion

3ms

Gut Microbiome and Hepatic Transcriptomic Determinants of HCC Development in Mice with Metabolic Dysfunction-Associated Steatohepatitis. (PubMed, J Hepatocell Carcinoma)

We identified microbiome components contributing to liver carcinogenesis by inducing inflammation, and changes in hepatic gene expression and hepatic cells distribution that contribute to tumor growth. Such information can be highly valuable for the development of new prevention strategies as well as of new biomarkers for risk modeling in HCC.

3 months ago

Preclinical • Journal

PTEN (Phosphatase and tensin homolog) • SPP1 (Secreted Phosphoprotein 1) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • IL10 (Interleukin 10)

PTEN deletion

3ms

Integrated multi-omics assessment of lineage plasticity in a prostate cancer patient with brain and dural metastases. (PubMed, NPJ Precis Oncol)

When analyzing pioneer transcription factors, the AMPC lesion exhibited elevated FOXA1 activity while the brain NEPC lesion showed elevated HOXC10, NFYB, and OTX2 expression suggesting novel roles in NEPC formation or brain tropism. Our results highlight the utility of performing multi-omic characterization, especially in rare cancer subtypes.

3 months ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • RB1 (RB Transcriptional Corepressor 1) • FOXA1 (Forkhead Box A1) • HOXC10 (Homeobox C10)

TP53 mutation • PTEN deletion • PTEN mutation • AR expression

3ms

Analysis of cancer multigene panel testing for osteosarcoma using the Center for Cancer Genomics and Advanced Therapeutics database in Japan (ESMO Asia 2024)

In this Japanese cohort, 42.2% of high-grade OSs had potentially actionable alterations per CKDB. Concurrent gene amplifications of KIT , KDR , and PDGFRA at 4q12, and VEGFA and CCND3 at 6p12-21, might offer promising therapeutic options for patients with recurrent/metastatic OS resistant to conventional chemotherapy.

3 months ago

Metastases

TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • KDR (Kinase insert domain receptor) • CDK4 (Cyclin-dependent kinase 4) • CCND3 (Cyclin D3) • NTRK (Neurotrophic receptor tyrosine kinase)

TMB-H • PTEN deletion • PTEN mutation • CDK4 amplification • NTRK fusion

FoundationOne® CDx • MSK-IMPACT • OncoGuide™ NCC Oncopanel System

8ms

Utility of Clinical Next Generation Sequencing Tests in KIT/PDGFRA/SDH Wild-Type Gastrointestinal Stromal Tumors. (PubMed, Cancers (Basel))

Compared to KIT/PDGFRA-mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy.

8 months ago

Journal • Next-generation sequencing • Stroma

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • ETV6 (ETS Variant Transcription Factor 6) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • AURKA (Aurora kinase A) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TP53 mutation • BRAF V600E • BRAF V600 • NTRK3 fusion • PTEN deletion • PTEN mutation • NF1 mutation • ETV6-NTRK3 fusion • CHEK2 mutation • PDGFRA mutation • FANCA mutation • FGFR1 fusion • FANCA deletion • PDGFR wild-type

imatinib

8ms

Immunohistochemical Findings and Clinicopathological Features of Breast Cancers with Pathogenic Germline Mutations in Non-BRCA Genes. (PubMed, Hum Pathol)

With PTEN and CHEK2 pathogenic mutations, abnormal IHC patterns are seen in early atypical proliferative lesions. IHC may be applied to identify CHEK2 &PTEN mutated BCs and precursor lesions.

8 months ago

Journal • BRCA Biomarker

PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)

ATM mutation • PTEN deletion • PTEN mutation • PALB2 mutation • CHEK2 mutation • ATM expression

9ms

Prognostic utility of biopsy-based PTEN and ERG status on biochemical progression and overall survival after SBRT for localized prostate cancer. (PubMed, Front Oncol)

The estimated 5-year OS rates were 93.9%, 100%, 80.0%, and 78.7% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. ERG rearrangements and PTEN deletions detected on biopsy samples are associated with poorer oncologic outcomes in prostate cancer patients treated with SBRT and merit further study in a dedicated prospective trial.

9 months ago

Journal • Biopsy

PTEN (Phosphatase and tensin homolog) • ERG (ETS Transcription Factor ERG) • TMPRSS2 (Transmembrane serine protease 2)

PTEN deletion • TMPRSS2-ERG fusion

9ms

Mutation of PTEN: Loss and Likelihood of Being a Non-responder to Trastuzumab in a Sample of Iraqi Her2+ Breast Cancer Patients. (PubMed, Cureus)

Loss of PTEN was also not linked to shifts in creatine kinase-myocardial band (CK-MB), troponin T (TnT), or any other biomarker, or troponin I (Tn1) at baseline or after 12 months of TRS therapy. These results give us important information about how PTEN deletion mutations might work as a predictor for TRS response in women with Her2+ BC.

9 months ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • PI3K (Phosphoinositide 3-kinases)

PTEN deletion

Herceptin (trastuzumab)

9ms

Amplification of different satellite-DNAs in prostate cancer. (PubMed, Pathol Res Pract)

Notably, these stretches included α-satellite DNA derived from chromosomes 2, 3, 4, 15, and 20, as well as satellite-III DNAs (D1Z1 and DYZ1). These findings align with recent discoveries indicating that α-satellite DNAs are expressed as long-non-coding RNAs in advanced cancer, particularly in the context of PCa.

9 months ago

Journal

PTEN (Phosphatase and tensin homolog) • ERG (ETS Transcription Factor ERG) • TMPRSS2 (Transmembrane serine protease 2)

PTEN deletion

9ms

PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1. (PubMed, J Transl Med)

This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration.

9 months ago

Journal

PTEN (Phosphatase and tensin homolog) • GOLM1 (Golgi Membrane Protein 1)

PTEN deletion • PTEN expression

9ms

BORXPTEN: Bortezomib in Patients With Metastatic Castration-Resistant Prostate Cancer With PTEN Deletion (clinicaltrials.gov)

P2, N=22, Recruiting, University of Utah | Not yet recruiting --> Recruiting

9 months ago

Enrollment open • Metastases

PTEN (Phosphatase and tensin homolog)

PTEN deletion

bortezomib

10ms

VARIATION IN PROSTATE CANCER GENOMIC SUBTYPES ACROSS PROSTATE MAGNETIC RESONANCE IMAGING PIRADS SCORES AND RACE (AUA 2024)

We examined common prostate cancer tumor subtypes and found marked heterogeneity across PIRADS lesions, with some variation between tumors from AA vs. non-AA. Our study not only highlights the correlation between tumor biology and MRI images, but it also raises the question of whether the biological differences in PCa between AA and non-AA are reflected differently on mpMRI, and if that means we should interpret these diagnostic studies differently in diverse populations.

10 months ago

MRI

PTEN (Phosphatase and tensin homolog)

ER positive • PTEN deletion

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

10ms

Myb overexpression synergizes with the loss of Pten and is a dependency factor and therapeutic target in T-cell lymphoblastic leukemia. (PubMed, Hemasphere)

We also showed that MYB is a dependency factor in T-ALL since RNA interference of Myb blocked cell cycle progression and induced apoptosis in both human and murine T-ALL cell lines. Finally, we provide preclinical evidence that targeting the transcriptional activity of MYB can be a useful therapeutic strategy for the treatment of T-ALL.

10 months ago

Journal

PTEN (Phosphatase and tensin homolog) • MYB (MYB Proto-Oncogene, Transcription Factor) • LMO2 (LIM Domain Only 2)

PTEN deletion • LMO2 overexpression

10ms

PTEN Deficiency Induces an Extrahepatic Cholangitis-Cholangiocarcinoma Continuum via Aurora kinase A in Mice. (PubMed, J Hepatol)

Pten deficiency in extrahepatic cholangiocytes and peribiliary glands led to a cholangitis-to-cholangiocarcinoma continuum through an Aurka-dependent manner. These findings offer new insights into preventive and therapeutic interventions for extrahepatic CCA.

10 months ago

Preclinical • Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • AURKA (Aurora kinase A) • PDX1 (Pancreatic And Duodenal Homeobox 1)

PTEN deletion • AURKA overexpression

10ms

Tumor Microenvironment and Genomic Profiling of Squamous Cell Carcinomas of the Breast (USCAP 2024)

About half of the breast SCCs exhibited high sTILs and positive PD-L1 expression, which indicated the potential opportunity for immunotherapy. Genomic profile revealed clinically meaningful alterations that might guide targeted treatment decisions in SCC patients.

10 months ago

Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • TERT (Telomerase Reverse Transcriptase) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)

PD-L1 expression • TP53 mutation • TMB-H • PIK3CA mutation • PTEN deletion • PTEN mutation • PD-L1 negative • TERT mutation • PIK3CA mutation + PTEN mutation • PIK3R1 mutation • TERT promoter mutation

PD-L1 IHC 22C3 pharmDx

11ms

Evaluation of potential biomarkers for lenvatinib plus pembrolizumab among patients with advanced endometrial cancer: results from Study 111/KEYNOTE-146. (PubMed, J Immunother Cancer)

This analysis demonstrated efficacy for lenvatinib plus pembrolizumab regardless of biomarker status. Results from this study do not support clinical utility of the evaluated biomarkers. Further investigation of biomarkers for this regimen is warranted.

11 months ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • Metastases

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog)

TP53 mutation • PIK3CA mutation • PTEN deletion • PTEN mutation • PIK3CA mutation + PTEN mutation

Keytruda (pembrolizumab) • Lenvima (lenvatinib)

11ms

Phase 2 Study of PI3K Inhibitor Copanlisib in Combination With Fulvestrant in Selected ER+ and/or PR+ Cancers With PI3K (PIK3CA, PIK3R1) and/or PTEN Alterations (clinicaltrials.gov)

P2, N=7, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2026 --> Aug 2024 | Trial primary completion date: Oct 2026 --> Aug 2024

11 months ago

Trial completion date • Trial primary completion date • Combination therapy

ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PI3K (Phosphoinositide 3-kinases)

ER positive • PIK3CA mutation • PTEN deletion • PIK3R1 mutation

fulvestrant • Aliqopa (copanlisib)

12ms

Phase 2 Study of PI3K Inhibitor Copanlisib in Combination With Fulvestrant in Selected ER+ and/or PR+ Cancers With PI3K (PIK3CA, PIK3R1) and/or PTEN Alterations (clinicaltrials.gov)

P2, N=7, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=78 --> 7

12 months ago

Enrollment closed • Enrollment change • Combination therapy

ER positive • PIK3CA mutation • PTEN deletion • PIK3R1 mutation

fulvestrant • Aliqopa (copanlisib)

almost1year

Development of a Genetically Engineered Mouse Model Recapitulating LKB1 and PTEN Deficiency in Gastric Cancer Pathogenesis. (PubMed, Cancers (Basel))

Moreover, this study endeavors to dissect the intricate ways in which these alterations contribute to the histopathologic advancement of gastric tumors, their potential for invasiveness and metastasis, their angiogenesis, and the evolving tumor stromal microenvironment. Our results show that conditional deletion of PTEN and LKB1 provides an ideal cancer microenvironment for G.C. tumorigenesis by promoting cancer cell proliferation, angiogenesis, and metastasis.

almost 1 year ago

Preclinical • Journal

PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDH1 (Cadherin 1)

PTEN deletion • CDH1 expression

1year

Neuronal deletion of phosphatase and tensin homolog in mice results in spatial dysregulation of adult hippocampal neurogenesis. (PubMed, Front Mol Neurosci)

We also observed region-specific increases in apoptotic cells in the dentate gyrus hilar region that paralleled the regional increases in Ki67+ cells. Our work is accordant with the literature showing that Pten serves as a negative regulator of dentate gyrus neurogenesis but adds temporal and spatial components to the existing knowledge.

1 year ago

Preclinical • Journal

PTEN (Phosphatase and tensin homolog)

PTEN deletion

1year

Borxpten: A phase II study of bortezomib (B) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with PTEN deletion. (ASCO-GU 2024)

Secondary Objectives: 1) To assess the antitumor activity of bortezomib in pts with mCRPC with PTEN deletion as assessed by PSA 50% response rate, duration of PSA response, PSA progression free survival (PFS), objective response rate, duration of response, radiographic PFS, PFS, and OS 2.) To assess the safety and tolerability of B in pts with mCRPC with PTEN deletion. Exploratory analysis: Concurrent PTEN and ATAD1 loss will be correlated with treatment responses with B. Clinical trial information: NCT06029998.

1 year ago

Clinical • P2 data • Metastases

PTEN (Phosphatase and tensin homolog)

PTEN deletion

bortezomib

1year

Source, co-occurrence, and prognostic value of PTEN mutations or loss in colorectal cancer. (PubMed, NPJ Genom Med)

Unexpectedly, PTEN deletions are associated with poor survival in MSS CRC, whereas PTEN mutations are associated with improved survival in MSI CRC. These and other data suggest use of PTEN as a prognostic marker is valid in CRC, but such use must consider driver mutation landscape, tumor subtype, and category of PTEN alteration.

1 year ago

Journal

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • PI3K (Phosphoinositide 3-kinases)

TP53 mutation • BRAF mutation • PTEN deletion • PTEN mutation • TP53 deletion

1year

Efficacy and Safety of Erdafitinib in Patients With High-grade and Low-grade Gliomas and Prespecified Fibroblast Growth Factor Receptor Alterations (FGFRalt) in the RAGNAR Trial (SNO 2023)

In HGG (glioblastoma, n=25 [83%]; median (m) age 54.5y [range 13-70]), 29 (97%) had FGFR fusions (FGFR3-TACC3, n=24); all (100%) underwent initial resection (if feasible) and received radiotherapy/chemotherapy per institution (eg, Stupp protocol); patients received median 2 prior therapies (range 1-6; 37% with prior bevacizumab). No treatment-related deaths occurred.ConclusionsErda demonstrated clinically meaningful activity in heavily pre-treated HGG/LGG with FGFRalt. Safety was consistent with known safety profile of erda.

1 year ago

Clinical

PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3)

PTEN deletion • PTEN mutation • FGFR1 mutation • FGFR fusion • FGFR1 fusion

Avastin (bevacizumab) • Balversa (erdafitinib)

1year

Differential Effect of Non-Steroidal Anti-Inflammatory Drugs Aspirin and Naproxen against TMPRSS2-ERG (Fusion)-Driven and Non-Fusion-Driven Prostate Cancer. (PubMed, Cancers (Basel))

Notably, there were no moderately differentiated (MD) adenocarcinomas in the dorsolateral prostate of naproxen groups, and its incidence also decreased by ~79-91% in the aspirin cohorts. In contrast, NSAIDs showed little protective effect against prostate tumorigenesis in Hi-Myc mice, suggesting that NSAIDs exert a specific protective effect against TMPRSS2-ERG (fusion)-driven PCa.

1 year ago

Journal

PTEN (Phosphatase and tensin homolog) • ERG (ETS Transcription Factor ERG)

PTEN deletion • TMPRSS2-ERG fusion

1year

Immunohistochemistry-Based Biomarkers and Impact on Outcomes Following Salvage Radiotherapy for Prostate Cancer. (PubMed, Int J Radiat Oncol Biol Phys)

PTEN loss identified by immunohistochemistry is an independent adverse prognostic factor for both biochemical and metastasis-free survival in prostate cancer patients treated with SRT. Although clinically validated RNA expression assays also exist which are prognostic for outcomes following SRT, stromal contamination in bulk RNA could mask "loss" signals specific to tumor cells, such as PTEN. Further work is necessary to determine the optimal approach to treating patients with poor molecular prognostic features in a salvage setting.

1 year ago

Journal

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

TP53 mutation • PTEN deletion • TP53 overexpression

over1year

BORXPTEN: Bortezomib in Patients With Metastatic Castration-Resistant Prostate Cancer With PTEN Deletion (clinicaltrials.gov)

P2, N=22, Not yet recruiting, University of Utah

over 1 year ago

New P2 trial • Metastases

PTEN (Phosphatase and tensin homolog)

PTEN deletion

bortezomib

over1year

Negative Confirmatory Biopsy Among Men on Active Surveillance for Prostate Cancer Along With PTEN/ERG as a Predictor of Pathologic Progression (CAP 2023)

Our study shows that negative B2 in men on AS is about 20% and these men have a reduced risk of pathologic progression in grade and tumor volume (>3 positive cores/>50% tumor in a single core), hence the intensity of their follow-up can be reduced. Low-risk PTEN/ERG profile is a reliable predictor of absence of disease progression and an indicator of low-grade disease.

over 1 year ago

Biopsy

PTEN (Phosphatase and tensin homolog) • ERG (ETS Transcription Factor ERG)

PTEN deletion

over1year

Genomic characterization between HER2-positive and negative gastric cancer patients in a prospective trial. (PubMed, Cancer Med)

According to the genomic profiling of HER2-positive and negative gastric cancer, several gene alterations in the HER2 pathway may be the potential mechanism underlying trastuzumab resistance. Relative to HER2-positive gastric cancer, HER2-negative gastric tumors with ARID1A mutation may be sensitive to immune checkpoint inhibitors.

over 1 year ago

Journal • Tumor mutational burden • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12)

HER-2 positive • TP53 mutation • HER-2 amplification • HER-2 negative • PTEN deletion • ARID1A mutation • CCNE1 amplification

Herceptin (trastuzumab)

over1year

Immunohistochemistry-Based Biomarkers and Impact on Outcomes Following Salvage Radiotherapy for Prostate Cancer (ASTRO 2023)

PTEN loss identified by immunohistochemistry is an independent adverse prognostic factor for both biochemical and metastasis-free survival in prostate cancer patients treated with SRT. Although clinically validated RNA expression assays also exist which are prognostic for outcomes following SRT, stromal contamination in bulk RNA could mask “loss” signals specific to tumor cells, such as PTEN. Further work is necessary to determine the optimal approach to treating patients with poor molecular prognostic features in a salvage setting.

over 1 year ago

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

TP53 mutation • PTEN deletion • TP53 overexpression

over1year

STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway. (PubMed, Mol Cancer)

Metformin, one of the most widely prescribed therapeutics against type 2 diabetes, inhibits mTORC1 in liver and requires LKB1 to mediate glucose homeostasis...Furthermore, PCa patients with high CREB expression have worse clinical outcomes and a significantly increased risk of PCa relapse and metastatic recurrence. In summary, we have shown that STAT3 controls mPCa via LKB1/pAMPK/mTORC1/CREB signaling, which we have identified as a promising novel downstream target for the treatment of lethal mPCa.

over 1 year ago

Journal • Metastases

PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • STAT3 (Signal Transducer And Activator Of Transcription 3)

PTEN deletion • AR expression • STAT3 expression

metformin

over1year

Inducible TgfbR1 and Pten deletion in a model of tongue carcinogenesis and chemoprevention. (PubMed, Cancer Gene Ther)

BRB administration resulted in reduced tumor growth, enhanced T-cell infiltration to the tongue tumor microenvironment and robust antitumoral CD8+ cytotoxic T-cell activity characterized by greater granzyme B and perforin expression. Our results demonstrate that intralingual injection of tamoxifen in Tgfβr1/Pten 2cKO mice results in discrete quantifiable tumors suitable for chemoprevention and therapy of experimental HNSCC.

over 1 year ago

Journal • IO biomarker

EGFR (Epidermal growth factor receptor) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • CD8 (cluster of differentiation 8) • BCL2L1 (BCL2-like 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • CD4 (CD4 Molecule) • GZMB (Granzyme B) • TGFB1 (Transforming Growth Factor Beta 1) • MMP9 (Matrix metallopeptidase 9) • PRF1 (Perforin 1) • TGFBR1 (Transforming Growth Factor Beta Receptor 1)

PTEN deletion • CTLA4 expression

tamoxifen

over1year

CLINICO-GENOMIC ANALYSIS OF KIT/PDGFRA/SDH WILD-TYPE GASTROINTESTINAL STROMAL TUMORS IDENTIFIES POTENTIAL DRIVER MUTATIONS (CTOS 2023)

The patient with ETV6-NTRK3 fusion was treated with larotrectinib for 28.7 months prior to progression, likely due to acquired NTRK3 gatekeeper mutation (F617L) rendering resistance to larotrectinib, then was on a second generation NTRK inhibitor, selitrectinib, for 16.5 months prior to progression. Triple negative GISTs comprise a diverse cohort with different driver mutations. Compared to KIT/PDGFRA mutant GIST, limited benefit was observed with imatinib in triple negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy.

over 1 year ago

Genomic analysis • Stroma • Omic analysis

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • ETV6 (ETS Variant Transcription Factor 6) • CHEK2 (Checkpoint kinase 2) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • AURKA (Aurora kinase A) • NTRK (Neurotrophic receptor tyrosine kinase) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

BRAF V600E • PIK3CA mutation • BRAF V600 • NTRK3 fusion • PTEN deletion • PTEN mutation • NF1 mutation • ETV6-NTRK3 fusion • CHEK2 mutation • PDGFRA mutation • FGFR1 fusion • PIK3CA I391M • PDGFR wild-type

Vitrakvi (larotrectinib) • imatinib • selitrectinib (BAY 2731954)

over1year

Gender Differences in a Mouse Model of Hepatocellular Carcinoma Revealed Using Multi-Modal Imaging. (PubMed, Cancers (Basel))

The liver uptake of F-TBD at 3 and 4.5 months was higher in the two female PTEN knockout mice that would eventually develop HCC and was the most predictive imaging biomarker for HCC in the female cohort. These studies demonstrate the diagnostic and prognostic role of multi-modal imaging in HCC mouse models and provide compelling evidence that disease progression in the PTEN knockout model is highly dependent on gender.

over 1 year ago

Preclinical • Journal

PTEN (Phosphatase and tensin homolog)

PTEN deletion • PTEN mutation

over1year

Ipatasertib and atezolizumab in cancers with increased PI3K-AKT pathway activity: First results from the CRAFT trial (ESMO 2023)

Conclusions Ipatasertib and atezolizumab were ineffective in this patient population with PI3K-AKT-altered tumors. More stringent molecular selection criteria and an addition trial arm were implemented (arm 5).

over 1 year ago

PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)

BRAF V600E • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • BRAF V600 • PTEN deletion • ALK rearrangement • BRAF V600K • AKT1 E17K • AKT1 mutation • ALK rearrangement + PIK3CA mutation

Tecentriq (atezolizumab) • ipatasertib (RG7440)

over1year

Hepatocellular carcinoma induced by hepatocyte Pten deletion reduces BAT UCP-1 and thermogenic capacity in mice, despite increasing serum FGF-21 and iWAT browning. (PubMed, J Physiol Biochem)

NASH and HCC were associated with elevated liver and serum FGF-21 content and iWAT UCP-1 expression (browning), but reduced serum insulin, leptin, and adiponectin levels and BAT UCP-1 content and expression of sympathetically regulated gene glycerol kinase (GyK), lipoprotein lipase (LPL), and fatty acid transporter protein 1 (FATP-1), which altogether resulted in an impaired whole-body thermogenic capacity in response to CL-316,243. In conclusion, FGF-21 pro-thermogenic actions in BAT are context-dependent, not occurring in NASH and HCC, and UCP-1-mediated thermogenesis is not a major energy-expending process involved in the catabolic state associated with HCC induced by Pten deletion in hepatocytes.

over 1 year ago

Preclinical • Journal

PTEN (Phosphatase and tensin homolog) • FGF21 (Fibroblast Growth Factor 21) • LPL (Lipoprotein Lipase) • LEP (Leptin)

PTEN deletion • FGF21 elevation