News - TP53 mutation + KRAS mutation

Mixed pancreatic ductal adenocarcinoma and well-differentiated neuroendocrine tumor: A case report. (PubMed, World J Gastrointest Oncol)

Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

2 days ago

Journal

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

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

Prevalence of HER3 Expression in Pancreatic Cancer Patients Treated With Systemic Chemotherapy. (PubMed, Cancer Med)

A high prevalence of HER3 expression was observed in pancreatic cancer patients after chemotherapy. Our findings indicate that HER3 is a potential therapeutic target for pancreatic cancer, deserving further clinical investigation.

9 days ago

Retrospective data • Journal

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)

TP53 mutation • KRAS mutation • ERBB3 expression • ERBB3 mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

12d

The role of epigenetic regulation in pancreatic ductal adenocarcinoma progression and drug response: an integrative genomic and pharmacological prognostic prediction model. (PubMed, Front Pharmacol)

The integration of epigenetic features with mutation profiles, immune microenvironment, and drug sensitivity offers new insights into PDAC heterogeneity and potential therapeutic strategies. These findings pave the way for personalized medicine in PDAC management and highlight the importance of epigenetic regulation in cancer research.

12 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

15d

Analysis of Methylation of Tumor-suppressive miRNAs and KRAS/TP53 Mutations in Pancreatic Juice. (PubMed, Anticancer Res)

Analyzing the methylation of miR-1247 in addition to KRAS and TP53 mutations in pancreatic juice may be useful to distinguish PC from PanIN/IPMN.

15 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MIR200A (MicroRNA 200a) • MIR1247 (MicroRNA 1247)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

18d

Biological and genetic characterization of a newly established human primary multidrug-resistant distal cholangiocarcinoma cell line, CBC3T-6. (PubMed, Sci Rep)

In addition, among the first-line anticancer drugs for cholangiocarcinoma, CBC3T-6 cells showed varying degrees of resistance to gemcitabine, oxaliplatin, cisplatin, and 5-FU...ABCB1 mutation as a possible therapeutic target for multidrug resistance. In conclusion, CBC3T-6 cells can be used as a useful tool to study the mechanism of cholangiocarcinoma and develop new therapeutic strategies for multidrug resistance.

18 days ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ABCB1 (ATP Binding Cassette Subfamily B Member 1)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • ABCB1 mutation

cisplatin • gemcitabine • 5-fluorouracil • oxaliplatin

A Rare Case of Primary Hepatic Undifferentiated Pleomorphic Sarcoma: Exploring Cancer-related Gene Mutations. (PubMed, Intern Med)

Despite initiating hepatic arterial infusion chemotherapy, the tumor continued to grow, and the patient's poor performance status complicated the transition to a phase I KRAS mutation drug trial, leading to death eight months after the symptom onset. A timely genetic mutation analysis may facilitate effective treatment transitions in hepatic UPS despite the lack of established treatments.

1 month ago

Journal

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

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

3ms

Combined KRAS and TP53 mutation in patients with colorectal cancer enhance chemoresistance to promote postoperative recurrence and metastasis. (PubMed, BMC Cancer)

Furthermore, advanced-stage patients with concurrent KRAS and TP53 mutations are susceptible to developing cancer-associated cachexia due to chemotherapy resistance or forced cessation of treatment. Our findings underscore the urgent need for the development of innovative and novel chemotherapeutic strategies to effectively manage colorectal cancer patients harboring combined KRAS and TP53 mutations.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CEACAM5 (CEA Cell Adhesion Molecule 5)

TP53 mutation • KRAS mutation • PIK3CA mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

3ms

Camrelizumab combined with chemotherapy for stage IV pulmonary sarcomatoid cancer with pancreatic metastases. (PubMed, Respir Med Case Rep)

Camrelizumab and chemotherapy were administered, and the metastasis disappeared. Immunotherapy combined with platinum-based chemotherapy is effective in treating PSC with pancreatic metastases.

3 months ago

Journal • PD(L)-1 Biomarker • IO biomarker • Metastases

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

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

AiRuiKa (camrelizumab)

3ms

Comprehensive genomic sequencing predicts sub-optimal response to bispecific antibodies (BsAb) and chimeric antigen receptor T cells (CAR-T) in multiple myeloma (MM) (IMW 2024)

BsAb and CAR-T may overcome individual standard genomic RF, however harboring multiple genomic RF remains adverse. Clinically available extended genomic characterization predicts response better than FISH alone in this large cohort treated with BsAb/CAR-T. This work will extend into pre-/post-therapy whole genome sequencing for more granular data analysis.

3 months ago

CAR T-Cell Therapy • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • TNFRSF17 (TNF Receptor Superfamily Member 17)

TP53 mutation • KRAS mutation • NRAS mutation • TP53 mutation + KRAS mutation • KRAS deletion

MSK-IMPACT Heme

7ms

LLS 2024 ELN-REFINED RISK STRATIFICATION IN OLDER ADULTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA TREATED WITH LOW-INTENSITY THERAPY (EHA 2024)

Among patients â‰¥60 yrs with ND AML given LIT, the current 2022 ELN risk system classifies most (79%)patients as adverse risk and does not reliably distinguish favorable from intermediate-risk, highlighting thelimitations of the model in this patient population. We propose a refined LLS classification using a "mutationscore" incorporating IDH2, MLL2, KRAS and TP53 mutations for those previously assigned ELN 2022 adverserisk, as well as redefining the definition of LLS-favorable risk.

7 months ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • KMT2D (Lysine Methyltransferase 2D) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2)

TP53 mutation • KRAS mutation • FLT3-ITD mutation • IDH2 mutation • FLT3 mutation • KMT2D mutation • TP53 mutation + KRAS mutation • MLL2 mutation • KRAS mutation + TP53 mutation

FoundationOne® Heme CDx • LeukoStrat® CDx FLT3 Mutation Assay

8ms

Identification and validation of a lactate metabolism-related six-gene prognostic signature in intrahepatic cholangiocarcinoma. (PubMed, J Cancer Res Clin Oncol)

Our study revealed the biological roles of LDHA in iCCA and developed a reliable lactate metabolism-related prognostic signature for iCCA, offering promising therapeutic targets for iCCA in the clinic.

8 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • LDHA (Lactate dehydrogenase A)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation

10ms

ctDNA improves prognostic prediction in relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone. (PubMed, Blood)

Serial analysis of ctDNA mutations in 94 cases revealed that TP53 and KRAS mutations frequently emerge after therapy. Thus, we clarify the genetic characteristics and clonal architecture of ctDNA mutations and demonstrate their superiority over BMPC mutations for prognostic prediction in RRMM.

10 months ago

Journal • Circulating tumor DNA

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog)

TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • ATM mutation • TP53 mutation + KRAS mutation

lenalidomide • Ninlaro (ixazomib)

10ms

Morindone as a potential therapeutic compound targeting TP53 and KRAS mutations in colorectal cancer cells. (PubMed, Chem Biol Interact)

In addition, gene knockdown has increased the number of apoptotic cells in both cell lines and further increment was observed after anthraquinone treatment. In conclusion, morindone could be a competitive therapeutic agent in CRC by exhibiting multiple mechanism of anti-cancer actions.

10 months ago

Journal

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

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • TP53 expression • KRAS expression

10ms

TGFβ-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma. (PubMed, EMBO Rep)

We propose a model whereby TGFβ induces LINC00313 in order to regulate the expression of hallmark Wnt pathway genes, in co-operation with SWI/SNF. By modulating key genes of the Wnt pathway, LINC00313 fine-tunes Wnt/TCF/LEF-dependent transcriptional responses and promotes cholangiocarcinogenesis.

10 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TGFB1 (Transforming Growth Factor Beta 1) • SULF2 (Sulfatase 2) • TCF7 (Transcription Factor 7)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

11ms

Targeted Combination Therapies: A New Frontier in the Treatment of TP53 and KRAS Mutation-Associated Cancers. (PubMed, ACS Med Chem Lett)

Researchers are exploring the effectiveness of these combined therapies in patient treatment and investigating their potential applications in drug manufacturing. With cancer being a global health challenge, these innovative strategies could present a breakthrough in enhancing survival rates and improving the quality of life for patients.

11 months ago

Journal • Combination therapy

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

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation

almost1year

Prognostic risk signature in patients with acute myeloid leukemia treated with hypomethylating agents and venetoclax. (PubMed, Blood Adv)

The mPRS classification accurately segregated groups of AML patients treated with HMA plus Ven. In these patients, N/KRAS and TP53 mutations appear to negatively impact outcomes and therefore new treatment approaches are warranted.

almost 1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3)

TP53 mutation • KRAS mutation • FLT3-ITD mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

Venclexta (venetoclax)

1year

Outcome of first-line treatment with pembrolizumab according to KRAS/TP53 mutational status for non-squamous PD-L1 high (≥50%) NSCLC in the German National Network Genomic Medicine Lung Cancer (nNGM). (PubMed, J Thorac Oncol)

G12C/TP53 co-mutations identify a subset of patients with a very favorable long-term survival with ICI monotherapy, mediated by highly active IFNγ signaling in a pro-inflammatory TME.

1 year ago

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

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • IFNG (Interferon, gamma)

PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • KRAS wild-type • KRAS G12 • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

Keytruda (pembrolizumab)

1year

Correlation analysis of clinical, pathological, imaging and genetic features of ground-glass nodule featured lung adenocarcinomas between high-risk and non-high-risk individuals. (PubMed, Eur J Med Res)

GGN-featured lung adenocarcinoma is dominated by non-high-risk female patients. Shorter preoperative follow-up in the non-high-risk group and no statistical difference in GGN detection way suggests the existing screening criteria for high-risk population may not suit GGN-featured lung cancer. In addition, the incidences of KRAS and TP53 mutations are higher in the high-risk group.

1 year ago

Retrospective data • Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)

TP53 mutation • KRAS mutation • EGFR mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

1year

Tumor-specific GPX4 degradation enhances ferroptosis-initiated antitumor immune response in mouse models of pancreatic cancer. (PubMed, Sci Transl Med)

N6F11 also sensitized immune checkpoint blockade that targeted CD274/PD-L1 in advanced cancer models, including genetically engineered mouse models of pancreatic cancer driven by KRAS and TP53 mutations. These findings may establish a safe and efficient strategy to boost ferroptosis-driven antitumor immunity.

1 year ago

Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • GPX4 (Glutathione Peroxidase 4) • HMGB1 (High Mobility Group Box 1)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

1year

3rd-Generation Tyrosine Kinase-Inhibitors and Azacitidine Are Safe and Effective in Myeloid Blast-Phase Chronic Myeloid Leukaemia and Result in a High Proportion of Subjects in 2nd Chronic Phase Able to Receive a Transplant (ASH 2023)

Purposes Study safety and efficacy of olverembatinib or ponatinib and azacitidine (AZA) in this setting. KRAS and TP53 mutations and PFKFB3::LINC02649 fusions had predictive impact on outcomes. Determining whether adding azacitidine to a 3rd-generation TKI requires a randomized controlled trial.

1 year ago

Clinical • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PFKFB3 (6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

Iclusig (ponatinib) • azacitidine • Nailike (olverembatinib)

1year

Targeted Protein Degradation for c-MYC Overcomes Therapy Resistance in T-Cell Acute Lymphoblastic Leukemias (ASH 2023)

GT19715 also enhanced cell death induced by dexamethasone. Targeted protein degradation of c-MYC induces promising anti-leukemia efficacy in T-ALL cells in vitro and in vivo. Further mechanistic and in vivo studies are ongoing.

1 year ago

IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • NOTCH1 (Notch 1) • CD8 (cluster of differentiation 8) • CRBN (Cereblon) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CD5 (CD5 Molecule) • BRD4 (Bromodomain Containing 4) • CD7 (CD7 Molecule)

TP53 mutation • KRAS mutation • PTEN mutation • MYC overexpression • BCL2 expression • CD8 expression • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

dexamethasone

1year

Local Control Following Stereotactic Body Radiation Therapy for Liver Oligometastases: Lessons from a Quarter Century. (PubMed, Curr Oncol)

However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g., KRAS and TP53 mutation), the use of systemic therapy prior to SBRT, the radiation dose, and the use of advanced technology and organ motion management during SBRT. These prognostic factors need to be considered when clinical trials are designed to evaluate the efficacy of SBRT for liver metastases.

1 year ago

Review • Journal

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

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

1year

TFEB activation in mediastinal lymph nodes: a potential modulator of immune response in NSCLC (SITC 2023)

Notably, overexpressing TFEB in CD11c+ dendritic cells augmented tumor-specific CD4 T-cell responses, yet reduced CD8 T-cell activities, suggesting a potential shift towards a tolerogenic immune environment in NSCLC. Conclusions Conclusively, our insights into TFEB’s function in NSCLC highlight the complex relationship between tissue-specific elements and tumor immunogenicity, offering avenues for refining immunotherapeutic strategies.

1 year ago

IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule) • ITGAX (Integrin Subunit Alpha X) • TFEB (Transcription Factor EB 2)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

over1year

Pancreatic ductal adenocarcinoma with a high expression of alcohol dehydrogenase 1B is associated with less aggressive features and a favorable prognosis. (PubMed, Am J Cancer Res)

PDAC patients with a high ADH1B expression had better disease-specific survival (DSS) and overall survival (OS) and ADH1B was an independent prognostic biomarker for both DSS (HR = 0.89, 95% CI = 0.80-0.99, P = 0.045) and OS (HR = 0.90, 95% CI = 0.82-0.99, P = 0.044) in multivariate analysis. In conclusion, PDAC with high ADH1B expression had less cell proliferation and malignant features, along with higher immune cell infiltration, and had a better prognosis.

over 1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • HRD (Homologous Recombination Deficiency) • CD8 (cluster of differentiation 8) • ALDH2 (Aldehyde Dehydrogenase 2 Family Member) • MKI67 (Marker of proliferation Ki-67) • ADH1B (Alcohol Dehydrogenase 1B (Class I), Beta Polypeptide)

TP53 mutation • KRAS mutation • HRD • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

over1year

Molecular analysis with pancreaseq® in evaluation and management of pancreatic cysts: A cohort of 28 patients. (PubMed, Cytojournal)

It was interpreted as serous cystadenoma and the risk for progression was low. Molecular analysis of pancreatic cysts with PancreaSeq® is useful in accurate diagnosis, especially when cytologic material is non-diagnostic and helps improve patient management.

over 1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • RNF43 (Ring Finger Protein 43) • VHL (von Hippel-Lindau tumor suppressor) • GNAS (GNAS Complex Locus)

TP53 mutation • KRAS mutation • ALK positive • ALK fusion • VHL mutation • RNF43 mutation • TP53 mutation + KRAS mutation • GNAS mutation • KRAS mutation + TP53 mutation

over1year

Human cytomegalovirus infection enhances 5‑lipoxygenase and cycloxygenase‑2 expression in colorectal cancer. (PubMed, Int J Oncol)

The CRC cell lines Caco‑2 and LS‑174T were infected with HCMV strain VR1814, treated with antiviral drug ganciclovir (GCV) and/or anti‑inflammatory drug celecoxib (CCX) and analyzed by reverse transcription‑quantitative PCR and immunofluorescence for 5‑LO, COX‑2, IE and pp65 transcripts and proteins. Treatment with GCV and CCX significantly decreased the transcript levels of COX‑2, 5‑LO, HCMV IE and pp65 in infected cells. HCMV was widely expressed in CRC and may promote inflammation and serve as a potential new target for CRC therapy.

over 1 year ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MSI (Microsatellite instability)

TP53 mutation • KRAS mutation • EGFR mutation • EGFR expression • TP53 mutation + KRAS mutation

celecoxib oral

over1year

Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis. (PubMed, Open Life Sci)

DNA damage repair and homologs recombinant repair deficiencies were significantly associated with high TMB in ICCA cases. In conclusion, we found that certain genetic mutations of TP53 and KRAS could predict poor prognosis in ICCA patients.

over 1 year ago

Journal • Tumor mutational burden

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden)

TP53 mutation • KRAS mutation • TMB-H • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

over1year

An amino acid metabolism-based seventeen-gene signature correlates with the clinical outcome and immune features in pancreatic cancer. (PubMed, Front Genet)

Moreover, high-AMRS group was also more sensitive to paclitaxel, cisplatin, and docetaxel. Overall, we constructed an AA-metabolism prognostic model, which provided a powerful prognostic predictor for the clinical treatment of pancreatic cancer.

over 1 year ago

Clinical data • Journal • Gene Signature • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8)

TP53 mutation • KRAS mutation • TMB-H • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

cisplatin • paclitaxel • docetaxel

over1year

Deciphering SWI/SNF complexes role in lung cancer using the Tuba-seq tool in a mouse model of lung adenocarcinoma (EACR 2023)

Barcoding sequencing will allow the determination of tumor number and size and, therefore, the assessment of this SWI/SNF subunits oncogenic potential. Further transcriptional experiments will allow us to identify the molecular pathways altered by SWI/SNF deficiency in our model.ConclusionWe have successfully generated all necessary tools to perform Tuba-seq experiments to study at the molecular level the role of SWI/SNF alteration in a mouse model of LUAD.

over 1 year ago

Preclinical

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ARID1B (AT-Rich Interaction Domain 1B) • ARID2 (AT-Rich Interaction Domain 2) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)

TP53 mutation • KRAS mutation • KRAS G12D • KRAS G12 • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

over1year

Molecular and functional heterogeneity of primary pancreatic neuroendocrine tumors and the metastases. (PubMed, Neuroendocrinology)

Metastases exhibited a certain extent of genomic and transcriptomic diversity from primary PanNETs. TP53 and KRAS mutation in primary samples might associate with metastasis and contribute to a poorer prognosis. A high fraction of novel targetable alterations enriched in metastases deserves to be validated in advanced PanNETs.

over 1 year ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • KMT2D (Lysine Methyltransferase 2D) • CDK4 (Cyclin-dependent kinase 4) • TSC2 (TSC complex subunit 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • FAT1 (FAT atypical cadherin 1) • TGFB1 (Transforming Growth Factor Beta 1)

TP53 mutation • KRAS mutation • MET amplification • EGFR amplification • ATM mutation • PTEN mutation • ARID1A mutation • TP53 mutation + KRAS mutation • TSC2 mutation • SMARCB1 deletion

over1year

Genomic landscape and clinical features of rare subtypes of pancreatic cancer: analysis with the national database of Japan. (PubMed, J Gastroenterol)

ACC clearly harbors different genomics compared with PDAC, possibly accounting for differences in treatment efficacy.

over 1 year ago

Retrospective data • Journal • BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium

over1year

Safety and efficacy of Sleeping Beauty TCR-T cells targeting shared KRAS and TP53 mutations expressed by solid tumors in first-in-human phase 1 study. (ASCO 2023)

This is the first-in-human experience administering Sleeping Beauty TCR-T cells. Signs of efficacy, safety and persistence of TCR-T cells was observed. Thus, this treatment has promise for patients with solid tumors expressing shared mutations in driver genes.

over 1 year ago

Clinical • P1 data • IO biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • HLA-A (Major Histocompatibility Complex, Class I, A)

TP53 mutation • KRAS mutation • EGFR mutation • KRAS G12D • KRAS G12V • KRAS G12 • TP53 R175H • TP53 mutation + KRAS mutation • HLA-A*02 • KRAS mutation + TP53 mutation

over1year

The genomic and transcriptomic landscapes of chemotherapy naïve vs post-chemotherapy germ cell tumors. (ASCO 2023)

Background: Cisplatin resistance occurs in up to 30% of patients with advanced germ cell tumors (GCTs)... This study provides evidence that chemo naïve GCTs with mutations in TP53, KRAS, KIT or MDM2 CNA have higher expression of genes associated with resistance to platinum-based chemotherapy. These findings contribute to a better understanding of the molecular characteristics of GCTs and may inform prognosis and treatment.

over 1 year ago

IO biomarker

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

TP53 mutation • KIT mutation • MDM2 amplification • TP53 mutation + KRAS mutation • MDM2 mutation • KRAS mutation + TP53 mutation

MI Tumor Seek™

cisplatin

over1year

p53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras. (PubMed, Oncotarget)

This was also the case in the context of additional activation of the Wnt signaling pathway. Thus, p53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras.

over 1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

over1year

LKB1-dependent regulation of TPI1 creates a divergent metabolic liability between human and mouse lung adenocarcinoma. (PubMed, Cancer Discov)

In mice, Ser21 of TPI1 is a Cys residue which can be oxidized to alter TPI1 activity without a need for SIKs or LKB1. Our findings suggest this metabolic flexibility is critical in rapidly growing cells with KRAS and TP53 mutations, explaining why loss of LKB1 creates a liability in these tumors.

over 1 year ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)

TP53 mutation • KRAS mutation • STK11 mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

over1year

Cell-free DNA Predicts Prolonged Response to Multi-agent Chemotherapy in Pancreatic Ductal Adenocarcinoma. (PubMed, Cancer Res Commun)

We report on the association of cfDNA with response durability for patients undergoing treatment with a novel metronomic chemotherapy regimen (gemcitabine, nab-paclitaxel, capecitabine, cisplatin, irinotecan; GAX-CI) for metastatic PDAC. This investigation offers encouraging evidence that cfDNA may prove to be a valuable diagnostic tool to guide clinical management.

over 1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CA 19-9 (Cancer antigen 19-9)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

cisplatin • gemcitabine • capecitabine • albumin-bound paclitaxel • irinotecan

over1year

SENESCENCE-BASED COLORECTAL CANCER SUBTYPING REVEALS DISTINCT MOLECULAT CHARACTERISTICS AND THERAPEUTIC STRATEGIES (DDW 2023)

We proposed the senescence subtypes of CRC for the first time and demonstrated the characteristics of different subtypes. We also found potential treatment interventions for each subtype, which can promote the precision treatment of CRC patients.

over 1 year ago

IO biomarker

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

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

almost2years

Concurrent KRAS and TP53 mutations in pancreatic cancer real-world data (RWD) highlight convergent tumor evolutionary patterns (AACR 2023)

Here we describe multiple independent combinations of KRAS and TP53 mutations leading to convergent functional outcomes for tumor cells, in the context of patient-specific gene mutation landscapes. Recurrent patterns of paired mutations with common cellular function dysregulation outcomes highlight core underlying mechanisms of pancreatic tumor evolution.

almost 2 years ago

Clinical • Real-world evidence • Real-world

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • SMAD4 (SMAD family member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

TP53 mutation • KRAS mutation • KRAS G12D • ARID1A mutation • KRAS G12V • KRAS G12 • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

almost2years

Spatial and longitudinal tumor heterogeneity in head and neck squamous cell carcinoma patients treated with primary surgery (AACR 2023)

Our study suggests spatial and longitudinal tumor heterogeneity and reports emerging mutations in ctDNA over time in HNSCC. Prognostic significance characterization of the ctDNA dominant clone allele frequency is ongoing.

almost 2 years ago

Clinical • Surgery

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • FAT1 (FAT atypical cadherin 1) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TP53 mutation • KRAS mutation • PIK3CA mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

OncoFOLLOW

almost2years

In vivo CRISPR screen identifies SOAT1 as a chemotherapy chemosensitizing target for non-small cell lung cancer (NSCLC) (AACR 2023)

Our results using CRISPR screening in vivo, identified SOAT1 as a critical therapeutic chemosensitizing target requiring only 50% inhibition of activity for sensitizing NSCLC to several chemotherapy agents routinely used in the clinic.

almost 2 years ago

Preclinical

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

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation

gemcitabine • paclitaxel • pemetrexed • etoposide IV