News - KRAS mutation - LARVOL VERI

22h

Phase I Trial of Adagrasib (MRTX849) in Combination With Cetuximab and Irinotecan in Patients With Colorectal Cancer (clinicaltrials.gov)

P1, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

22 hours ago

Enrollment closed

KRAS (KRAS proto-oncogene GTPase) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)

KRAS mutation • KRAS G12C • KRAS G12

Erbitux (cetuximab) • irinotecan • Krazati (adagrasib)

T-cell dependency of tumor regressions and complete responses with RAS(ON) multi-selective inhibition in preclinical models of PDAC. (PubMed, Cancer Discov)

RAS(ON) multi-selective inhibitors, such as daraxonrasib (RMC-6236) and RMC-7977, target the active state of RAS, with potent anti-tumor activity in PDAC murine models. Moreover, the combination of RAS(ON) multi-selective inhibitors with immunotherapy conferred deeper and more durable tumor regressions, including complete responses not seen with either treatment alone. In summary, concurrent inhibition of mutant and wild-type RAS is active in concert with T cell immunotherapy, revealing RAS(ON) multi-selective inhibitors as a potential therapeutic immuno-sensitizing strategy in PDAC.

1 day ago

Preclinical • Journal • IO biomarker

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • RAS wild-type

daraxonrasib (RMC-6236) • RMC-7977

Real world experience with MET inhibitors in MET exon 14 skipping mutated non-small cell lung cancer: largest Indian perspective. (PubMed, Discov Oncol)

MET TKI showed higher systemic and intracranial efficacy with manageable safety profile. The current study represents an unmet need for more clinical phase 3 study for rare genomic alterations as well as patient access programs in the Indian subcontinent.

1 day ago

Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

TP53 mutation • KRAS mutation • MET exon 14 mutation

Adenomyosis associated with endometrial cancer: Possible correlation with pathological, immunohistochemical and molecular characteristics. (PubMed, Gynecol Oncol)

Adenomyosis was associated with a lower prevalence of FIGO stage ≥IB disease, deep myometrial invasion, lymphovascular invasion, and extrauterine spread. These findings suggest that structural changes in the myometrial microenvironment may play a role in limiting tumor invasiveness and spread, warranting further investigation.

1 day ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation

Multi-gene panel sequencing reveals the relationship between driver gene mutation and clinical characteristics in lung adenocarcinoma. (PubMed, Discov Oncol)

This work revealed the mutational landscape and characteristics of 30 core driver genes in a LUAD cohort. Co-mutated genes and genes associated with gender and age indicate their different roles in the corresponding subgroup of the LUAD.

3 days ago

Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NF1 (Neurofibromin 1) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TP53 mutation • KRAS mutation • EGFR mutation • EGFR L858R • EGFR exon 19 deletion

Structural insights, regulation, and recent advances of RAS inhibitors in the MAPK signaling cascade: a medicinal chemistry perspective. (PubMed, RSC Med Chem)

Only two RAS inhibitors, sotorasib and adagrasib, have been approved by the FDA, and several are in clinical trials. This review comprises recent developments in synthetic RAS inhibitors, their unique properties, their importance in inhibiting RAS mutations, and the current challenges in developing new RAS inhibitors. This review will undoubtedly help researchers design novel RAS inhibitors.

4 days ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)

KRAS mutation • RAS mutation

Lumakras (sotorasib) • Krazati (adagrasib)

Longitudinal profiling of IDH-mutant astrocytomas reveals acquired RAS-MAPK pathway mutations associated with inferior survival. (PubMed, Neurooncol Adv)

Patients whose IDH-mutant astrocytomas harbored these oncogenic RAS-MAPK pathway alterations had inferior survival compared to those with RAS-MAPK wild-type tumors. These findings highlight novel genetic perturbations in the RAS-MAPK pathway as a likely mechanism contributing to the high-grade transformation and treatment resistance of IDH-mutant astrocytomas that may be a potential therapeutic target for affected patients and used for future risk stratification.

4 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)

KRAS mutation • BRAF mutation • CDKN2A deletion

KEYNOTE E27: Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C) (clinicaltrials.gov)

P1/2, N=540, Recruiting, Eli Lilly and Company | Trial completion date: Jun 2026 --> Apr 2027 | Trial primary completion date: Jun 2026 --> Apr 2027

4 days ago

Trial completion date • Trial primary completion date

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Keytruda (pembrolizumab) • Erbitux (cetuximab) • cisplatin • carboplatin • pemetrexed • olomorasib (LY3537982)

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)

P1, N=1200, Recruiting, Amgen | Trial completion date: Mar 2028 --> Dec 2027

5 days ago

Trial completion date

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Keytruda (pembrolizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)

Integrating epidemiology and genomics data to estimate the prevalence of acquired cysteine drug targets in the U.S. cancer patient population. (PubMed, Pharmacogenomics J)

Non-epidemiologically informed pan-cancer estimation of mutation rates may not be representative of the number of cancer patients with a specific mutation. Our study suggests that epidemiological and genomic information should be combined when estimating the population level abundance of specific pathogenic mutations.

5 days ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Transcriptional regulation by LKB1 in lung adenocarcinomas: Exploring oxidative stress, neuroglial and amino acid signatures. (PubMed, Biochem Biophys Res Commun)

Notably, LUAD patients with mutated LKB1 showed gene expression patterns indicative of oxidative stress, defective neuronal-glial and neuroinflammation programs, and altered amino acid homeostasis. These changes resemble the roles LKB1 plays in neural crest stem cells, suggesting that LKB1 may reduce tumor aggressiveness in LUAD by maintaining a developmental gene expression program.

5 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)

KRAS mutation • STK11 mutation

Discovery of mutations predictive of survival benefit from immunotherapy in first-line NSCLC: A retrospective machine learning study of IMpower150 liquid biopsy data. (PubMed, Comput Biol Med)

Predictive mutations and combinations were identified for overall survival (OS) improvement with atezolizumab plus bevacizumab plus carboplatin and paclitaxel (ABCP) compared to bevacizumab plus carboplatin and paclitaxel (BCP). In summary, the proposed machine-learning tool identified potential predictive biomarkers for first-line chemoimmunotherapy in NSCLC and can be readily applied to other tumor types and studies. It can also be extended to explore predictive biomarkers beyond mutations.

5 days ago

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

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • FAT1 (FAT atypical cadherin 1) • GNAS (GNAS Complex Locus)

KRAS mutation • HER-2 mutation • KRAS wild-type • KEAP1 mutation • RAS wild-type

Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • paclitaxel

Integrated Profiling Delineated KIF18A as a Significant Biomarker Associated with Both Prognostic Outcomes and Immune Response in Pancreatic Cancer. (PubMed, Immunotargets Ther)

In addition, the high expression of KIF18A is positively related to ferroptosis and m6A genes expression, and its high expression is driven by mutated KRAS and TP53. This study confirmed that KIF18A can be used as a marker to predict the prognosis and immunotherapy of PAAD, and it participates in the formation of microtubules in PAAD cells and promotes the malignant behavior of PAAD.

6 days ago

Journal • Tumor mutational burden • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • KIF18A (Kinesin Family Member 18A)

TP53 mutation • KRAS mutation

Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05) (clinicaltrials.gov)

P2, N=137, Active, not recruiting, Daiichi Sankyo | Trial completion date: Dec 2024 --> Dec 2025

7 days ago

Trial completion date

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) • NTRK (Neurotrophic receptor tyrosine kinase)

KRAS mutation • EGFR mutation • MET exon 14 mutation

Datroway (datopotamab deruxtecan)

Clinicopathological significance of DICER1 mutation in follicular thyroid carcinoma (PubMed, Zhonghua Bing Li Xue Za Zhi)

However, TERT-promoter mutation was found in 6 DICER1-wild-type cases (8.8%, 6/68), with 3 cases also having RAS hotspot mutations and exhibiting highly aggressive biological behaviors. DICER1 mutations may occur in FTCs and appear mutually exclusive with RAS and TERT-promoter mutations, warranting further study as RAS-like mutations.

7 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase) • RAS (Rat Sarcoma Virus) • DICER1 (Dicer 1 Ribonuclease III)

KRAS mutation • NRAS mutation • RAS mutation • HRAS mutation

Design, Production, and Optimization of Antigen-Specific Recombinant Antitumor Dimeric IgA Antibody. (PubMed, Methods Mol Biol)

Recent work has established that dimeric IgA antibodies can target intracellular targets inside cancer cells expressing the polymeric immunoglobulin receptor (pIgR). Here, we thoroughly discuss the entire process of recombinant production of intracellular antigen-specific dimeric IgA antibodies that could be utilized for targeting oncodrivers inside tumor cells.

7 days ago

Journal • IO biomarker

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation

Mutational Analysis of Bile Cell-Free DNA in Primary Sclerosing Cholangitis: A Pilot Study. (PubMed, Liver Int)

Mutational analysis of cfDNA obtained from bile collected from PSC patients undergoing ERCP is feasible. Implementing the Bilemut assay may help identify patients needing closer surveillance and further imaging studies.

7 days ago

Journal

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

TP53 mutation • KRAS mutation

Oncomine™ Pan-Cancer Cell-Free Assay

Respiratory tract involvement in Rosai-Dorfman disease - A report of two distinct cases. (PubMed, Heliyon)

While there was no in situ recurrence at the resected site, the untreated tracheal lesions initially progressed at the first four months of follow-up but remained stable at the ten-month follow-up. These cases illustrate the variability and potential progression of RDD, and highlight the promising application of bronchoscopic treatment for managing respiratory involvement in RDD.

7 days ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS wild-type • RAS wild-type

Liquid biopsy for evaluating mutations and chromosomal aberrations in cerebrospinal fluid from patients with primary or metastatic CNS tumors. (PubMed, J Liq Biopsy)

Serial samples from 14 patients demonstrate that CSF LBx can be used for monitoring therapy efficacy. LBx using CSF is clinically reliable and provides informative results in a substantial proportion of patients with metastatic CNS tumors and to a lesser degree in patients with primary CNS tumors.

7 days ago

Journal • Liquid biopsy

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

KRAS mutation • EGFR mutation • PIK3CA mutation • ESR1 mutation

The role of molecular biomarkers in the diagnosis, prognosis, and treatment stratification of oral squamous cell carcinoma: A comprehensive review. (PubMed, J Liq Biopsy)

Better patient outcomes will eventually result from earlier identification, more precise prognostication, and individualised therapy regimens made possible by advancements in biomarker research. For these biomarkers to be widely used, further research must be done on verifying them and incorporating them into standard clinical practice.

7 days ago

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

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • CCND1 (Cyclin D1) • CDH1 (Cadherin 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)

KRAS mutation • EGFR mutation • EGFR expression

NGS detection of gene rearrangements and METexon14 mutations in liquid biopsy of advanced NSCLC patients: A study of two Italian centers. (PubMed, J Liq Biopsy)

ctDNA testing to detect oncogenic fusions or METexon14 mutations in advanced NSCLC patients is useful, even if type of gene alterations and clinical characteristics could influence the driver detection rate. Liquid biopsy represents a complementary tool to tissue genotyping, however more sensitive approaches for gene fusions and METexon14 detection are needed to implement its strength and reliability.

7 days ago

Journal • Liquid biopsy • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • SMAD4 (SMAD family member 4)

TP53 mutation • KRAS mutation • NRAS mutation • ALK positive • RET fusion • ALK rearrangement • ALK fusion • ALK mutation • ROS1 fusion • ROS1 positive • ROS1 rearrangement • RET positive

AVENIO ctDNA Expanded Kit

Reprogramming the Tolerogenic Immune Response Against Pancreatic Cancer Metastases by Lipid Nanoparticles Delivering a STING Agonist Plus Mutant KRAS mRNA. (PubMed, ACS Nano)

Importantly, the immune response could also be adoptively transferred by injecting splenocytes (containing memory T cells) from treated into nontreated recipient mice. This study demonstrates that reprogramming the immune-protective niche for metastatic pancreatic cancer can be achieved by the delivery of a STING agonist and mutant KRAS mRNA via ionizable LNPs, offering both prophylactic and therapeutic advantages.

8 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)

KRAS mutation • KRAS G12D • RAS wild-type • KRAS G12

Basroparib overcomes acquired resistance to MEK inhibitors by inhibiting Wnt-mediated cancer stemness in KRAS-mutated colorectal cancer. (PubMed, Biochem Pharmacol)

Mechanistically, basroparib suppressed Wnt-mediated cancer stemness, a bypass mechanism for acquired resistance to MEK inhibitors in KRAS-mutated CRC. This study provides the first preclinical evidence of the relevance of basroparib in treating CRC with acquired resistance to MEK inhibitors due to APC and KRAS mutations, possibly by reducing the Wnt-mediated cancer stemness.

8 days ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • APC (APC Regulator Of WNT Signaling Pathway)

KRAS mutation • KRAS G12D • KRAS wild-type • KRAS G13D • KRAS G13

basroparib (STP1002)

Small molecules for Kirsten rat sarcoma viral oncogene homolog mutant cancers: Past, present, and future. (PubMed, Eur J Pharmacol)

However, due to the lack of a binding pocket, KRAS has long been considered an undruggable target in recent decades until the discovery of Sotorasib (AMG510). With the approval of Glecirasib (JAB-21822), there are three approved small molecule inhibitors of KRAS, all of which are KRAS G12C inhibitors. At the same time, the limited clinical benefits and rapid emergence of drug resistance to the approved inhibitors have also promoted the emergence of more therapeutics, such as tri-complexes and proteolysis-targeting chimeras (PROTAC). In this paper, we summarize the development of KRAS inhibitors (KRASG12C, KRASG12D, and KRASmulti inhibitors, PROTAC, and tri-complex) and discuss the challenges and opportunities in the discovery of KRAS inhibitors in the hope of providing insights into the development of novel medications for KRAS.

8 days ago

Preclinical • Review • Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • mTOR (Mechanistic target of rapamycin kinase)

KRAS mutation • KRAS G12D

Lumakras (sotorasib) • glecirasib (JAB-21822)

Design, synthesis and biological evaluation of pyrrolopyrimidine urea derivatives as novel KRASG12C inhibitors for the treatment of cancer. (PubMed, Eur J Med Chem)

Importantly, the in vivo test results show that compound SK-17 has a superior PK profile and lower toxicity in zebrafish test. These results demonstrated the potential of SK-17 with novel scaffold as a promising lead compound targeting KRASG12C to guide in-depth structural optimization.

8 days ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C

Dynamic Monitoring of Circulating Tumor DNA to Predict the Risk of Non In Situ Recurrence of Postoperative Glioma: A Prospective Cohort Study. (PubMed, Cancer Med)

In glioma patients undergoing primary surgery, dynamic monitoring of ctDNA and genotyping can be used for early risk stratification, efficacy monitoring, and early recurrence detection, and provide a basis for clinical research to evaluate early therapeutic intervention.

9 days ago

Journal • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • NF1 (Neurofibromin 1) • MUC16 (Mucin 16, Cell Surface Associated) • CHEK2 (Checkpoint kinase 2)

TP53 mutation • KRAS mutation • EGFR mutation • CHEK2 mutation

10d

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

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

10 days ago

Journal

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

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

oxaliplatin

11d

A Study of VS-6766 and Cetuximab in Patients With Advanced Colorectal Cancer (clinicaltrials.gov)

P1/2, N=53, Suspended, University of Chicago | Recruiting --> Suspended

11 days ago

Trial suspension

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • MSI (Microsatellite instability)

KRAS mutation • MSI-H/dMMR

Erbitux (cetuximab) • avutometinib (VS-6766)

11d

Humanized mouse models of KRAS-mutated colorectal and pancreatic cancers with HLA-class-I match for pre-clinical evaluation of cancer immunotherapies. (PubMed, Oncoimmunology)

As cytotoxic T lymphocyte (CTL) activity underlies many immunotherapies, we developed more clinically relevant KRAS-mutated CRC and PDAC humanized cancer models using transgenic NRG-A2 mice expressing HLA-A2.1 to enable HLA-class-I match between mouse tissues (including the thymus), the humanized immune system and human tumors. Using these novel humanized cancer models and a CTL-mediated combination (immuno)therapy with clinical potential, we were able to recapitulate the complexity and therapy-induced changes reported in patient biopsies, demonstrating the use of these HLA-matched models for pre-clinical validation of novel immunotherapies.

11 days ago

Preclinical • Journal • IO biomarker

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation

11d

Relationships between Molecular Genetics and Clinical Features of Children with Acute Myeloid Leukemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

Gene mutations are common in children with AML, and next-generation sequencing can significantly improve the detection rate of gene mutations, which can guide the risk stratification therapy. In addition, FLT3-ITD and KIT mutations may no longer be poor prognostic factors.

11 days ago

Retrospective data • Journal

KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • GATA2 (GATA Binding Protein 2)

KRAS mutation • NRAS mutation • FLT3-ITD mutation • KIT mutation

11d

Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in China. (PubMed, J Cancer Res Clin Oncol)

KRAS mutations were most frequent in cancers of the digestive, female reproductive, and respiratory systems. Specific KRAS mutations are associated with TMB and MSI in various cancer types.

11 days ago

Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker • Pan tumor

KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)

KRAS mutation • TMB-H • MSI-H/dMMR • KRAS G12C • KRAS G12D • KRAS G13D • KRAS G12 • KRAS G13

12d

Feature Selection and Network-Driven Analyses to Unveil Common RNA Signatures in Colon and Pancreatic KRAS-Mutant Cancers. (PubMed, Cancer Med)

Our findings may provide insight into the common transcriptional signatures potentially underlying colon and pancreatic KRAS-mutant cancers. However, further studies are needed to elucidate the diagnostic and prognostic value of targets identified as common features in our study.

12 days ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS wild-type

12d

Prognostic Significance of STK11/LKB1 Expression and Its Role in the Tumor Microenvironment of Colorectal Adenocarcinoma. (PubMed, In Vivo)

While STK11/LKB1 expression is associated with tumor progression and survival outcomes, there is no evidence that STK11/LKB1 expression influences the infiltration of lymphocytes into the tumor microenvironment.

12 days ago

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

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)

KRAS mutation • STK11 mutation

12d

Outcomes Post-laparoscopic Intervention for Accessory and Cavitated Uterine Masses: A Review and a Molecular Insight. (PubMed, Gynecol Obstet Invest)

These results demonstrated that laparoscopic surgical approaches are effective and frequently the first surgical approach chosen for the treatment of ACUM, but that techniques to treat these conditions are not standardized. This case is the first to demonstrate mutations in ACUM, suggesting a potential role for cancer-associated somatic mutations in their genesis. Future developments in this area may include sending more of these samples for genetic analysis, improving our understanding of how these lesions are formed, while also working to standardize how they are removed.

12 days ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • HRAS (Harvey rat sarcoma viral oncogene homolog)

KRAS mutation • PIK3CA mutation • FGFR2 mutation • RET mutation • HRAS mutation • KRAS G12S • NRAS G12

12d

Genomic and micro-environmental insights into drug resistance in colorectal cancer liver metastases. (PubMed, Discov Oncol)

This study reveals how genomic and TME-driven factors contribute to drug resistance in CRC liver metastases. Integrating these insights with clinical data could advance precision therapies, addressing the evolving challenge of tumor drug resistance in CRC.

12 days ago

Journal • IO biomarker

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

TP53 mutation • KRAS mutation • PIK3CA mutation

12d

The Pharmacologic Inhibition of KRAS Mutants as a Treatment for Cancer: Therapeutic Principles and Clinical Results. (PubMed, Dtsch Arztebl Int)

Pharmacological KRAS inhibition is a promising new approach to the treatment of many kinds of cancer.

12 days ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C

docetaxel • Vectibix (panitumumab) • Lumakras (sotorasib) • Stivarga (regorafenib) • Krazati (adagrasib)

12d

Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN (clinicaltrials.gov)

P1, N=100, Recruiting, Jacqueline Garcia, MD | Trial primary completion date: Feb 2025 --> Dec 2025

12 days ago

Trial primary completion date

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • DEK (DEK Proto-Oncogene) • RIT1 (Ras Like Without CAAX 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • KRAS mutation • NRAS mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • CBL mutation • Chr del(5q)

Venclexta (venetoclax) • azacitidine • Inqovi (decitabine/cedazuridine) • fludarabine IV • busulfan

13d

Enhancing PDAC therapy: Decitabine-olaparib synergy targets KRAS-dependent tumors. (PubMed, iScience)

The combination was especially effective in dKRAS-PDAC with a BRCA2 mutation, preventing metastasis growth. Our results support the clinical evaluation of DEC+OLA in PDAC.

13 days ago

Journal • BRCA Biomarker • PARP Biomarker

KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

KRAS mutation • BRCA wild-type

Lynparza (olaparib) • decitabine

13d

Revisiting Variation in the Somatic Mutation Landscape of Non-Small Cell Lung Cancer. (PubMed, HGG Adv)

Finally, we provided insights into the intrinsic and extrinsic covariates associated with the NSCLC somatic mutation landscape; while confirming associations with ethnicity (TP53, EGFR), NSCLC subtype (14 genes including KRAS, NFE2L2, STK11), and smoking history (KRAS, CSMD3, TP53), we dismissed gene-level associations with sex when other covariates are controlled for. The results presented here represent a concise up-to-date summary of variation in the somatic mutation landscape and carry importance for NSCLC geneticists, medical practitioners, and drug discovery scientists.

13 days ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CSMD3 (CUB And Sushi Multiple Domains 3)

TP53 mutation • KRAS mutation

13d

Recent Anti-KRASG12D Therapies: A "Possible Impossibility" for Pancreatic Ductal Adenocarcinoma. (PubMed, Cancers (Basel))

Novel anti-KRASG12D therapies have been developed for solid-organ tumors, including small compounds, pan-RAS inhibitors, protease inhibitors, chimeric T cell receptors, and therapeutic vaccines. This comprehensive review summarizes current knowledge on the biology of KRAS-driven PDAC, the latest therapeutic options that have been experimentally validated, and developments in ongoing clinical trials.

13 days ago

Review • Journal • IO biomarker

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12D • KRAS G12

13d

Correlation of GNAS Mutational Status with Oncologic Outcomes in Patients with Resected Intraductal Papillary Mucinous Neoplasms. (PubMed, Cancers (Basel))

WT GNAS, mutant P53, and mutant KRAS each correlate with recurrence and decreased survival. Further studies are required to validate these preliminary observations.

13 days ago

Journal

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

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

13d

The Prognostic Impact of Additional Molecular and Cytogenetic Abnormalities on AML Patients with NPM1- and/or FLT3-ITD Mutations Receiving Intensive Chemotherapy: Real-World Data from the Greek Registry. (PubMed, Cancers (Basel))

revealed that allo-SCT in CR1 improved the outcomes (EFS and OS) in Groups 2 and 3, but had no additional impact in Group 1. Age, primary refractory disease and allogenic stem cell transplantation in the first complete response were found to have a prognostic impact on outcomes, Interestingly, no significant association was detected between the poor prognostic cytogenetic abnormalities or the presence of additional mutations in myeloid genes, MDS-related genes or KRAS/NRAS genes and the outcomes in any group of patients.

13 days ago

Journal • Real-world evidence

KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NPM1 (Nucleophosmin 1)

KRAS mutation • NRAS mutation • FLT3-ITD mutation • NPM1 mutation