Massive parallel sequencing and personalized therapeutic targets for personalized mutational status might allow patients with adenosquamous carcinomas to improve survival at the different levels of progression. Adapted criteria in the classification recognized by WHO 2021, which tumoural cellular level sub-classification might be a particular sub-typing with particular outcomes as exemplified in the present mutational exercise. This small series, defined after routine IHC classification correlated with tumoural heterogeneity/clonality previewed for adenosquamous carcinoma.

3 months ago

Clinical

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1)

TP53 mutation • KRAS mutation • EGFR mutation • HER-2 amplification • PIK3CA mutation • HER-2 mutation • EGFR amplification • ALK mutation • MET mutation • NTRK3 mutation

Oncomine Precision Assay

5ms

Comprehensive genomic profiling provides patients access to novel matched therapies in a diverse real-world cohort of advanced lung cancer patients (ESMO 2024)

In a real-world, retrospective analysis of a cohort of advanced NSCLC patients, most oncologists utilized CGP to identify and treat patients with guideline-recommended variant matched targeted therapy, with adherence rates varying by variant. Importantly, even patients that received CGP results prior to FDA approval of novel therapies, received matched therapy once they were included in guidelines.

5 months ago

Real-world evidence • Clinical • Real-world • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • EGFR exon 19 deletion • RET fusion • ALK fusion • RET mutation • ROS1 fusion • MET mutation • KRAS G12 • NTRK1 mutation • ALK-ROS1 fusion • NTRK3 mutation

Tempus xT Assay

8ms

Poorly Differentiated Thyroid Cancer: A Rare Entity (ENDO 2024)

Tyrosine kinase inhibitors i.e, sorafenib and lenvatinib, have been used in cases of progressive, recurrent, or metastatic disease not responsive to 131I therapy. PDTC accounts for 3â€“5% of all thyroid carcinomas. The 5, 10-, and 15-year survival rates of patients are 50â€“85%, 34â€“50%, and 0%, respectively. RAS gene alterations are found in 25â€“35%, BRAF mutation in 15â€“27%, TERT promoter mutation in 40% and mutant TP53 in 16â€“28% of PDTCs.

8 months ago

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

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TERT (Telomerase Reverse Transcriptase) • NKX2-1 (NK2 Homeobox 1)

PD-L1 expression • TP53 mutation • BRAF V600E • BRCA1 mutation • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • RET mutation • TERT mutation • NTRK1 mutation • TERT promoter mutation • NTRK3 mutation

OmniSeq INSIGHT

sorafenib • Lenvima (lenvatinib)

1year

B Targeted Therapy Matched To Genomic Alterations (Brafv600E, Ntrk, Fgfr, Ros1, Pik3Ca, Pten) In Patients With Recurrent Idh Wildtype Glioblastoma: A Real-Life Cohort Analysis From Veneto Institute Of Oncology, Padua (Italy) (EANO 2023)

All patients received radiotherapy and temozolomide as first-line therapy...TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts)... Our results confirm the activity of dabrafenib/trametinib in BRAFV600E mutant glioblastoma pts and might suggest deeper explorations in targeting ROS1 and FGFR. Further correlation among patients' outcome, molecular characteristics and TT timing are still under investigation.

1 year ago

Clinical • PD(L)-1 Biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • FGFR (Fibroblast Growth Factor Receptor) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ROS1 fusion • FGFR1 fusion • IDH wild-type • NTRK1 mutation • PIK3CA mutation + PTEN mutation • NTRK3 mutation

FoundationOne® CDx

Mekinist (trametinib) • Tecentriq (atezolizumab) • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • temozolomide • Piqray (alpelisib) • Balversa (erdafitinib) • ipatasertib (RG7440)

over1year

A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)

P1/2, N=280, Recruiting, DualityBio Inc. | Not yet recruiting --> Recruiting

over 1 year ago

Enrollment open • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CD276 (CD276 Molecule)

BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ALK rearrangement • MET exon 14 mutation • ROS1 rearrangement • MET mutation • RET rearrangement • KRAS G12 • NTRK1 mutation • NTRK3 mutation

BNT324

over1year

Racial Diversity and Co-Mutational Analysis of Biologically Relevant Alterations in EGFR Mutant Lung Cancers (IASLC-WCLC 2023)

Significant differences in the prevalence of EGFR alterations were observed across races, with specific co-mutations like KMT2C and GLI1 occurring more frequently in AA compared to CA and API patients. KMT2C may be linked to higher TMB and immunotherapy response, while GLI1 has been shown to be involved in erlotinib resistance. Variabilities in alterations across races may inform more effective treatment strategies for LCa patients.

over 1 year ago

Tumor mutational burden • IO biomarker

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RB1 (RB Transcriptional Corepressor 1) • KMT2C (Lysine Methyltransferase 2C) • GLI1 (GLI Family Zinc Finger 1)

TP53 mutation • EGFR mutation • TMB-H • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • KMT2C mutation • NTRK3 mutation

Tempus xT Assay

erlotinib

over1year

A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)

P1/2, N=280, Not yet recruiting, DualityBio Inc.

over 1 year ago

New P1/2 trial • Metastases

BNT324

over1year

Hidden in Plain Sight: Incidental Diagnosis of Metastatic Papillary Thyroid Microcarcinoma without Radiologically-Apparent Thyroid Tumor (AACE 2023)

She is currently on 150 mcg of levothyroxine and doing well clinically...This case is unusual in that nodal metastasis were present even without a sizable primary thyroid tumor. Although more studies are needed to elucidate the clinical and prognostic significance of NTRK fusion mutations in PTMC, their response to TRK inhibitors may represent a future pathway for treatment.

over 1 year ago

Metastases

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase) • TG (Thyroglobulin)

NTRK3 fusion • NTRK3 mutation • NTRK fusion

almost2years

Molecular determinants of KRAS p.G12C inhibitor efficacy in advanced NSCLC (AACR 2023)

Background: Irreversible allosteric KRAS p.G12C inhibitors (KG12Ci) such as sotorasib and adagrasib have revolutionized the therapeutic landscape of advanced KG12C-mutant NSCLC, however individual responses are heterogeneous and curtailed by innate and adaptive/acquired resistance. Co-mutations in KEAP1, SMARCA4 and CDKN2A/2B define subgroups of KG12C NSCLC pts with markedly distinct outcomes with KG12Ci monotherapy. Tailoring of KG12C inhibitor-anchored therapeutic strategies and patient stratification should take into account the co-mutation status of individual tumors.

almost 2 years ago

Clinical • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler) • DAXX (Death-domain associated protein) • PI3K (Phosphoinositide 3-kinases)

KRAS G12C • BRAF mutation • PTEN mutation • STK11 mutation • ALK mutation • KEAP1 mutation • CDKN2A mutation • KRAS G12 • SMARCA4 mutation • NTRK1 mutation • NTRK3 mutation

Lumakras (sotorasib) • Krazati (adagrasib)

2years

Interplay between Tumor Mutational Burden and Mutational Profile and Its Effect on Overall Survival: A Pilot Study of Metastatic Patients Treated with Immune Checkpoint Inhibitors. (PubMed, Cancers (Basel))

Combining TMB and mutation profiles in key cancer genes can better qualify patients for ICI treatment and predict their OS.

2 years ago

Journal • Checkpoint inhibition • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • STK11 (Serine/threonine kinase 11) • RNF43 (Ring Finger Protein 43) • ZFHX3 (Zinc Finger Homeobox 3) • NT5C (5', 3'-Nucleotidase, Cytosolic) • TENT5C (Terminal Nucleotidyltransferase 5C) • E2F3 (E2F transcription factor 3)

TMB-H • STK11 mutation • RNF43 mutation • NTRK3 mutation

Keytruda (pembrolizumab)

2years

PAPILLARY THYROID CARCINOMA: A PROGRESSIVE CASE WITH ASSOCIATED RARE NTRK3 MUTATION (ATA 2022)

He was then started on daily levothyroxine for hormone replacement...Further surgery and radiation not recommended currently in favor of lab surveillance, but patient may be Larotrectinib (tropomyosin kinase receptor inhibitors) candidate given his mutation...Adjuvant radioactive iodine therapy is the next step after surgery. Routine cervical lymph node dissection remains a subject of debate with regards to the recurrence rate.

2 years ago

Clinical

BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • TG (Thyroglobulin)

BRAF mutation • NTRK3 mutation

Vitrakvi (larotrectinib)

over2years

NTRK3 mutation affects the efficacy of immune checkpoint inhibitors in patients with advanced cancer (ESMO 2022)

Conclusions Our study founded that patients with cancer harboring NTRK3 mutation tended to have higher TMB and longer OS for the first time. In the future, relevant prospective clinical trials need to be designed to verify this conclusion.

over 2 years ago

Clinical • Checkpoint inhibition • Tumor Mutational Burden • IO biomarker

TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3)

TMB-H • TMB-L • NTRK3 mutation

over2years

APT-CUBE: A Study to Investigate the Safety, Pharmacokinetics, and Clinical Activity of AP203 in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion to Selected Malignancies (clinicaltrials.gov)

P1/2, N=168, Not yet recruiting, AP Biosciences Inc.

over 2 years ago

New P1/2 trial

PD-L1 expression • BRAF V600E • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET mutation • RET rearrangement • NTRK1 mutation • NTRK3 mutation

AP203

over2years

Genetic ancestry differences in tumor mutation in early and average-onset colorectal cancer. (ASCO 2022)

The use of genetic ancestry instead of categorical race/ethnicity provides a more quantitative and precise profile of shared genetic background that can underlie biological race differences in CRC cancer etiology and outcomes.

over 2 years ago

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • APC (APC Regulator Of WNT Signaling Pathway)

TP53 mutation • KRAS mutation • BRAF mutation • APC mutation • NTRK3 mutation • TP53 mutation + NTRK3 mutation

Tempus xT Assay

almost3years

Entrectinib Induces Apoptosis and Inhibits the Epithelial-Mesenchymal Transition in Gastric Cancer with NTRK Overexpression. (PubMed, Int J Mol Sci)

Entrectinib treatment significantly reduced expression levels of phosphorylated NFκB, AKT, ERK, and β-catenin in NCI-N87 and AGS cells, whereas it upregulated the expression levels of ECAD in NCI-N87 cells. Together, these results suggest that entrectinib has anti-cancer activity not only in GC cells overexpressing pan NTRK but also in VEGFR2 GC cells via the inhibition of the pan NTRK and VEGFR signaling pathways.

almost 3 years ago

Journal

PD-L1 (Programmed death ligand 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase) • TGFBR1 (Transforming Growth Factor Beta Receptor 1)

PD-L1 expression • KDR expression • NTRK1 mutation • NTRK3 mutation • NTRK expression

Rozlytrek (entrectinib)

almost3years

Unique Molecular Signatures are Associated with Aggressive Histology in Pediatric Differentiated Thyroid Cancer. (PubMed, Thyroid)

Among our cohort of pediatric TC patients with comprehensive MT, >90% had an identifiable genetic alteration. Aggressive features were primarily associated with BRAF-like gene fusions. Preoperative MT results may be useful in guiding the extent of initial operation in pediatric patients (age<19 years) with TC.

almost 3 years ago

Clinical • Journal

BRAF (B-raf proto-oncogene) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6)

BRAF mutation • NTRK3 fusion • ETV6-NTRK3 fusion • NTRK3 mutation