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BIOMARKER:

RAS mutation

21h
Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas. (PubMed, Genes (Basel))
All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87-1), miR-221 (AUC 0.79, 95% CI 0.68-0.9), miR-222 (AUC 0.76, 95% CI 0.63-0.89), and miR-15a (AUC 0.85, 95% CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs (p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation (p < 0.001) and miR-146b (p = 0.016) and miR-221 (p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.
Journal
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BRAF (B-raf proto-oncogene) • RAS (Rat Sarcoma Virus) • MIR221 (MicroRNA 221) • MIR16 (MicroRNA 16) • MIR146B (MicroRNA 146b) • MIR15A (MicroRNA 15a) • MIR222 (MicroRNA 222)
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BRAF mutation • RAS mutation
21h
Activation of MAP Kinase Pathway by Polyisoprenylated Cysteinyl Amide Inhibitors Causes Apoptosis and Disrupts Breast Cancer Cell Invasion. (PubMed, Biomedicines)
The movement of the cells through the Matrigel was also inhibited by 74% after PCAIs exposure, which could have been due to the depleted levels of F-actin and vinculin punctate, resulting in the shrinkage of the cells by 76%, thereby impeding cell movement. These results show promise for PCAIs as potential therapies for TNBC as they significantly inhibit the hallmark processes and pathways that promote cell proliferation, migration, and invasion, which result in poor prognoses for breast cancer patients.
Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • VCL (Vinculin) • BAK1 (BCL2 Antagonist/Killer 1) • RASA1 (RAS P21 Protein Activator 1)
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RAS mutation
22h
HER2-Positive Metastatic Colorectal Cancer. (PubMed, Curr Treat Options Oncol)
At present, standard of care first-line treatment for those with HER2-positive mCRC remains chemotherapy in combination with epidermal growth factor receptor (EGFR) inhibitors or bevacizumab, depending on RAS/BRAF mutational status and tumor sidedness...While the choice of anti-HER2 therapy is empiric given lack of head-to-head comparisons, the combination of trastuzumab plus tucatinib has received FDA accelerated approval for use in this setting and is generally the authors' preference. Trastuzumab plus lapatinib, trastuzumab plus pertuzumab, and trastuzumab deruxtecan (T-DXd) also have evidence of efficacy in this setting...These include the optimal sequence of anti-HER2 therapies with chemotherapy and anti-EGFR therapies, the optimal combination partners for anti-HER2 therapies, and the incorporation of predictive biomarkers to guide use of anti-HER2 therapies. Results of ongoing studies may thus alter the treatment paradigm above in the coming years.
Review • Journal • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene)
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HER-2 positive • HER-2 overexpression • BRAF mutation • HER-2 amplification • HER-2 mutation • BRAF wild-type • RAS mutation • EGFR positive
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Avastin (bevacizumab) • lapatinib • Perjeta (pertuzumab) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Tukysa (tucatinib)
1d
Different oncogenes and reproductive histories shape the progression of distinct premalignant clones in multistage mouse breast cancer models. (PubMed, Am J Pathol)
However, parity decreased the overall prevalence of tumors bearing Krasmut, and the magnitude of this decrease depended on both the number and timing of pregnancies. These multistage models may be useful for elucidating biological features of premalignant mammary neoplasia.
Preclinical • Journal
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RAS (Rat Sarcoma Virus)
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KRAS mutation • NRAS mutation • PIK3CA H1047R • RAS mutation • HRAS mutation • NRAS Q61 • MYC expression • NRAS Q61L • KRAS Q61L
5d
Unraveling the Genetic Web: H-Ras Expression and Mutation in Oral Squamous Cell Carcinoma-A Systematic Review. (PubMed, Head Neck Pathol)
This review sheds light on the prevalence of H-Ras mutations, their association with clinical characteristics, and their potential implications for OSCC prognosis. It also enhances our comprehension of the molecular mechanisms that underlie OSCC and paves the way for further research into targeted treatments based on H-Ras alterations.
Review • Journal
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RAS (Rat Sarcoma Virus)
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RAS mutation
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Zarnestra (tipifarnib)
5d
Oncocytoid Salivary Tumors: Differential Diagnosis and Utility of Newly Described Immunohistochemistry. (PubMed, Head Neck Pathol)
Oncocytoid salivary tumors may have overlapping morphologies, posing diagnostic challenges for pathologists. Recently described immunohistochemical markers may offer valuable tools for diagnosing and potentially guiding treatment options for these tumors.
Journal
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NR4A3 (Nuclear receptor subfamily 4 group A member 3)
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BRAF V600E • BRAF V600 • RAS mutation
8d
Selumetinib and Cyclosporine in Treating Patients With Advanced Solid Tumors or Advanced or Metastatic Colorectal Cancer (clinicaltrials.gov)
P1, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025
Trial completion date • Metastases
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BRAF (B-raf proto-oncogene) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • MAPK1 (Mitogen-activated protein kinase 1)
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BRAF mutation • RAS mutation
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Koselugo (selumetinib) • cyclosporin A microemulsion
10d
PALBOCICLIB + PD-0325901 for NSCLC & Solid Tumors (clinicaltrials.gov)
P1, N=60, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | Phase classification: P1/2 --> P1 | N=139 --> 60
Trial completion • Phase classification • Enrollment change • Combination therapy
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KRAS (KRAS proto-oncogene GTPase) • RAS (Rat Sarcoma Virus)
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KRAS mutation • RAS mutation
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Ibrance (palbociclib) • mirdametinib (PD-0325901)
10d
An effective two-stage NMBzA-induced rat esophageal tumor model revealing that the FAT-Hippo-YAP1 axis drives the progression of ESCC. (PubMed, Cancer Lett)
Here, we report the usage of multi-kinase inhibitor sorafenib as a tumor promoter to establish an efficient two-stage NMBzA-induced rat ESCC carcinogenesis model, resulting in increments of tumor incidences and shortened tumor formation times...Multi-omic analyses indicate that NMBzA-induced rat ESCCs are accompanied by progressive hyperactivations of the FAT-Hippo-YAP1 axis and siRNA or inhibitors of YAP1 block the growth of rat ESCCs. Taken together, these studies provide a framework of using an effective rat ESCC model to investigate multilevel functional genomics of ESCC carcinogenesis, which justify targeting YAP1 as a therapeutic strategy for ESCC.
Preclinical • Journal
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YAP1 (Yes associated protein 1)
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RAS mutation
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sorafenib
11d
Characterization of Ras Y4H mutants in Drosophila. (PubMed, MicroPubl Biol)
In humans, rare histidine substitution mutations at Y4 are found in HRas in cerebellar glioblastomas (cGBMs). We report here that analogous Y4H mutations in Drosophila Ras make it less sensitive to Rabex-5-mediated ubiquitination in cells and show increased frequency of vein phenotypes per wing compared to wild-type Ras, which would be consistent with Ras gain-of-function and with their appearance in human cGBMs.
Journal
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HRAS (Harvey rat sarcoma viral oncogene homolog) • RAS (Rat Sarcoma Virus)
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RAS mutation • RAS wild-type • HRAS mutation
12d
Gluing GAP to RAS Mutants: A New Approach to an Old Problem in Cancer Drug Development. (PubMed, Int J Mol Sci)
As a proof of concept, we identify two new, drug-like small molecules with the new method; these compounds specifically inhibit the growth of the PANC-1 cell line with KRAS mutation G12D in vitro and in vivo. Importantly, the two new compounds show significantly lower IC50 and higher specificity against the G12D KRAS mutant human pancreatic cancer cell line PANC-1, as compared to the recently described selective G12D KRAS inhibitor MRTX-1133.
Journal
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KRAS (KRAS proto-oncogene GTPase) • RAS (Rat Sarcoma Virus)
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KRAS mutation • KRAS G12D • RAS mutation • KRAS G12
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MRTX1133
12d
Exploiting the therapeutic implications of KRAS inhibition on tumor immunity. (PubMed, Cancer Cell)
However, achieving this synergy in the clinical setting has proven challenging. Here, we explore how understanding the impact of RAS mutant tumor cells on the TME can guide innovative approaches to combining RAS inhibition with immunotherapies, review progress in both pre-clinical and clinical stages, and discuss challenges and future directions.
Review • Journal • IO biomarker
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KRAS (KRAS proto-oncogene GTPase)
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RAS mutation
14d
Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases. (PubMed, Int J Hyperthermia)
In both cohorts, the nomogram demonstrated good discrimination and calibration. The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.
Journal
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RAS (Rat Sarcoma Virus)
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RAS mutation
14d
Review • Journal
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RAS (Rat Sarcoma Virus)
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KRAS mutation • NRAS mutation • RAS mutation • NRAS G13
14d
A Study to Evaluate Safety, Efficacy, and Pharmacokinetics in Participants With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=110, Recruiting, Eutilex | Trial completion date: Feb 2025 --> Dec 2025 | Trial primary completion date: Sep 2023 --> Sep 2025
Trial completion date • Trial primary completion date • Metastases
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ALK (Anaplastic lymphoma kinase) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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MSI-H/dMMR • RAS mutation
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EU101
16d
Association of Squamous Cell Carcinoma and Hyaluronan: A Scope of the Literature. (PubMed, Eplasty)
One of the proposed mechanisms associated with this tumor resistance has been the accumulation of high-molecular-weight hyaluronic acid (HMWHA) in the epidermis. Researchers were able to conclude that the CD44/HMWHA interaction mediates cancer cell apoptosis and restricts cell cycle progression as a mechanism of cancer resistance in naked mole rats.
Review • Journal • IO biomarker
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
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RAS mutation
16d
Pancreatic Cancer Treatment Targeting the HGF/c-MET Pathway: The MEK Inhibitor Trametinib. (PubMed, Cancers (Basel))
However, resistance remains a challenge, necessitating ongoing research to counteract the resistance mechanisms. This review offers an in-depth exploration of the HGF/c-MET signaling pathway, trametinib's mechanism, clinical applications, combination strategies, and future directions in the context of pancreatic cancer.
Review • Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
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BRAF mutation • RAS mutation
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Mekinist (trametinib)
16d
Recent Advances in Therapeutic Strategies to Improve Colorectal Cancer Treatment. (PubMed, Cancers (Basel))
The use of fluoropyrimidine (FP)-based chemotherapy regimens to treat mCRC continues to evolve contributing to improved long-term survival. Future advances in chemotherapy for mCRC will need to position development relative to the advances made in precision oncology.
Review • Journal
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BRAF (B-raf proto-oncogene)
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EGFR mutation • BRAF mutation • RAS mutation
16d
Focus on RAS Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis. (PubMed, Cancers (Basel))
At a median follow up of 96.2 months, the median OS for codon 61 RAS-mutated patients was significantly shorter compared to RAS/BRAF wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 RAS-mutated and BRAF V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 RAS mutations and metastatic involvement of the peritoneum and ovary.
Retrospective data • Journal • Metastases
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BRAF (B-raf proto-oncogene) • RAS (Rat Sarcoma Virus)
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BRAF V600E • BRAF V600 • BRAF wild-type • RAS mutation • RAS wild-type
16d
Impact of KRASG12 mutations on survival with trifluridine/tipiracil plus bevacizumab in patients with refractory metastatic colorectal cancer: post hoc analysis of the phase III SUNLIGHT trial. (PubMed, ESMO Open)
The presence of a KRASG12 mutation had no detrimental effect on OS among patients treated in SUNLIGHT. The benefit of FTD/TPI plus bevacizumab over FTD/TPI alone was confirmed independently of KRASG12 status.
P3 data • Retrospective data • Journal • Metastases
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • RAS mutation • KRAS G12R • KRAS G12
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Avastin (bevacizumab) • Lonsurf (trifluridine/tipiracil)
17d
Exploring Molecular Genetic Alterations and RAF Fusions in Melanoma: A Belvarafenib Expanded Access Program in Patients with RAS/RAF-Mutant Melanoma. (PubMed, Oncologist)
Our study highlights the value of NGS in detecting BRAF, NRAS mutations and RAF fusions, expanding possibilities for targeted therapies in malignant melanoma. Belvarafenib showed clinical benefit in patients harboring these alterations. Ongoing trials will provide further insights into the safety and efficacy of belvarafenib.
Journal
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BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
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BRAF mutation • NRAS mutation • RAS mutation
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belvarafenib (RG6185)
17d
Trial completion date • Combination therapy • Metastases
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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KRAS mutation • EGFR L858R • ALK rearrangement • RAS mutation
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Keytruda (pembrolizumab) • docetaxel • Lenvima (lenvatinib)
17d
Trial completion date • Metastases
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BRAF (B-raf proto-oncogene) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • MAPK1 (Mitogen-activated protein kinase 1)
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BRAF mutation • RAS mutation
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Koselugo (selumetinib) • cyclosporin A microemulsion
17d
STRATEGIC-1: Multi-Line Therapy Trial in Unresectable Metastatic Colorectal Cancer (clinicaltrials.gov)
P3, N=464, Active, not recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Recruiting --> Active, not recruiting | Trial completion date: Jun 2021 --> Dec 2024 | Trial primary completion date: Jun 2021 --> Jul 2023
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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NRAS mutation • KRAS wild-type • RAS mutation • RAS wild-type • NRAS wild-type • KRAS exon 3 mutation • KRAS exon 4 mutation
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Avastin (bevacizumab) • Erbitux (cetuximab) • 5-fluorouracil • Vectibix (panitumumab) • capecitabine • oxaliplatin • irinotecan • leucovorin calcium
18d
Evolving survival gains in patients with young-onset colorectal cancer and synchronous resectable liver metastases. (PubMed, Eur J Surg Oncol)
On multivariate analysis, hepatectomy in the CE was independently associated with improved overall survival (HR 0.48, p = 0.001). With a combination of perioperative systemic therapy, careful selection of treatment approach, and coordinated resections, durable cure can be achieved in YOCRC patients.
Journal
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BRAF (B-raf proto-oncogene) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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BRAF mutation • RAS mutation
18d
Myotubularin-related-protein-7 inhibits mutant (G12V) K-RAS by direct interaction. (PubMed, Cancer Lett)
In mouse models of gastric and intestinal cancer, a cell-permeable MTMR7-CC mimicry peptide decreased tumour growth, Ki67 proliferation index and ERK1/2 nuclear positivity. Thus, MTMR7 mimicry peptide(s) could provide a novel strategy for targeting mutant K-RAS in cancers.
Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • FOS (Fos Proto-Oncogene AP-1 Transcription Factor Subunit 2)
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KRAS mutation • KRAS G12V • RAS mutation • KRAS G12
21d
Phase 1/2 study of combined BCL-xL and MEK inhibition with navitoclax and trametinib in KRAS or NRAS mutant advanced solid tumors. (PubMed, Clin Cancer Res)
Navitoclax in combination with trametinib was tolerable. Durable clinical responses were observed in patients with RAS-mutant GYN cancers, warranting further evaluation in this population.
P1/2 data • Journal • Metastases
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCL2L1 (BCL2-like 1)
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KRAS mutation • NRAS mutation • RAS mutation • BCL2L1 mutation
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Mekinist (trametinib) • navitoclax (ABT 263)
22d
The relationship between clinical and pathological findings and FDG - PET uptake in metastatic colorectal cancers. (PubMed, Indian J Cancer)
We could not demonstrate a significant association between KRAS mutation and SUVmax values of PET scan in primary or metastatic tumor sites in advanced CRC.
Journal • Metastases
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • CEACAM5 (CEA Cell Adhesion Molecule 5) • RAS (Rat Sarcoma Virus) • CA 19-9 (Cancer antigen 19-9)
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KRAS mutation • BRAF mutation • RAS mutation
22d
Concurrent NRAS-BRAF variants in metastatic colorectal cancer: a Tunisian case report. (PubMed, Anticancer Drugs)
Therefore, RAS and BRAF mutations were considered exclusive. Herein, we describe a novel concomitant NRAS/BRAF mutation identified in a series of 865 colorectal cancer patients.
Journal • Metastases
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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KRAS mutation • BRAF mutation • NRAS mutation • RAS mutation
22d
NAUTILUS: OKI-179 Plus Binimetinib in Patients With Advanced Solid Tumors in the RAS Pathway (Phase 1b) and NRAS-mutated Melanoma (Phase 2) (clinicaltrials.gov)
P1/2, N=36, Active, not recruiting, OnKure, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b --> P1/2 | N=73 --> 36
Enrollment closed • Phase classification • Enrollment change • Metastases
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BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NF1 (Neurofibromin 1) • GNAQ (G Protein Subunit Alpha Q)
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NRAS mutation • RAS mutation
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Mektovi (binimetinib) • bocodepsin (OKI-179)
23d
Strain-release alkylation of Asp12 enables mutant selective targeting of K-Ras-G12D. (PubMed, Nat Chem Biol)
The recently approved non-small cell lung cancer drugs sotorasib and adagrasib covalently capture an acquired cysteine in K-Ras-G12C mutation and lock it in a signaling-incompetent state. Structural insights from X-ray crystallography and exploitation of the stereoelectronic requirements for attack of the electrophile allowed development of a substituted malolactone that resisted attack by aqueous buffer but rapidly crosslinked with the aspartate-12 of K-Ras in both GDP and GTP state. The GTP-state targeting allowed effective suppression of downstream signaling, and selective inhibition of K-Ras-G12D-driven cancer cell proliferation in vitro and xenograft growth in mice.
Journal
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KRAS (KRAS proto-oncogene GTPase) • RAS (Rat Sarcoma Virus)
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KRAS mutation • KRAS G12C • KRAS G12D • RAS mutation • KRAS G12
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Lumakras (sotorasib) • Krazati (adagrasib)
23d
Characterization of somatic copy number deletion of chromosome 22q in papillary thyroid carcinoma (AACR 2024)
RNA sequencing gene expression analysis based on 22qDEL status revealed downregulation of most genes residing on chromosome 22q and significant differential expression activity of immune-related genes, further implicating a role of immune dysregulation in PTC. Our study suggests that 22qDEL may not act as a primary driver of PTC but plays an important role as a co-factor of RAS point mutations, which could further drive PTC development.
RAS (Rat Sarcoma Virus) • CHEK2 (Checkpoint kinase 2)
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RAS mutation
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MSK-IMPACT
23d
Assessing the clinical value of ctDNA sequencing for initial tumor profiling in metastatic colorectal cancer patients with sufficient tumor tissue (AACR 2024)
In addition, the fold changes in ctDNA dynamics during treatment significantly correlated with changes in tumor size and CEA levels, as well as with droplet digital PCR copy number fold changes. In a patient with MET amplification, ctDNA NGS identified MET Y1230H as a potential acquired resistance mutation after crizotinib treatment, which responded to cabozantinib but not to capmatinib.Conclusions Initial tumor profiling using ctDNA NGS yielded outcomes comparable to those of tumor tissue NGS in guiding treatment for patients with newly diagnosed mCRC, thereby suggesting its utility as an initial profiling method in mCRC.
Clinical • MSi-H Biomarker • Circulating tumor DNA • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • FGFR1 (Fibroblast growth factor receptor 1) • NF1 (Neurofibromin 1) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • APC (APC Regulator Of WNT Signaling Pathway)
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TP53 mutation • KRAS mutation • MSI-H/dMMR • BRAF mutation • MET amplification • RAS mutation
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AlphaLiquid® 100
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Xalkori (crizotinib) • Cabometyx (cabozantinib tablet) • Tabrecta (capmatinib)
28d
YAP/TEAD involvement in resistance to paclitaxel chemotherapy in lung cancer. (PubMed, Mol Cell Biochem)
The half-maximal inhibitory concentration (IC50) of paclitaxel or trametinib, which are Mitogen-Activated protein kinase and Erk Kinase (MEK) inhibitors, combined with a YAP/TEAD inhibitor (IV#6), was determined. The YAP/TEAD inhibitor restored paclitaxel sensitivity of A549R cells cultured in a 3D microfluidic system, with lung cancer cells from a fresh tumor efficiently killed by YAP/TEAD inhibitor/paclitaxel doublet. Evidence of the YAP/TEAD transcriptional program's role in chemotherapy resistance paves the way for YAP therapeutic targeting.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • RAS mutation
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Mekinist (trametinib) • paclitaxel
28d
Current advances in targeted therapy for metastatic colorectal cancer - Clinical translation and future directions. (PubMed, Cancer Treat Rev)
The pivotal trials of cetuximab in combination with BRAF/ MEK inhibitor for BRAF V600E mutant mCRC, and panitumumab with KRAS G12C inhibitor in KRAS(G12C)-mutant mCRC have been practice-changing. The non-invasive monitoring of molecular resistance to targeted therapies using Next Generation Sequencing analysis of circulating tumor-derived DNA (ctDNA) and captured sequencing of tumors have improved patient selection for targeted therapies. This review will focus on how latest advances, challenges and future directions in the development of targeted therapies in mCRC.
Review • Journal • Metastases
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
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BRAF V600E • KRAS mutation • HER-2 amplification • BRAF V600 • BRAF wild-type • RAS mutation
|
Erbitux (cetuximab) • Vectibix (panitumumab)
30d
Assessment of RAS-RAF-MAPK Pathway Mutation Status in Healthy Skin, Benign Nevi, and Cutaneous Melanomas: Pilot Study Using Droplet Digital PCR. (PubMed, Int J Mol Sci)
Here, we demonstrate that the "young" ddPCR technology is as effective as a CE-IVD marked real-time PCR method for detecting BRAF V600 hotspot mutations in tumor biopsies and recommend it for extended use in clinical settings. Moreover, ddPCR was able to detect low-frequency hotspot mutations, such as NRAS G12/G13, in our tissue specimens, which makes it a promising tool for investigating the mutational landscape of sun-damaged skin, benign nevi, and melanomas in more extensive clinical studies.
Journal • Tumor mutational burden
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BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
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BRAF mutation • NRAS mutation • BRAF V600 • RAS mutation • NRAS G12 • NRAS G13 • NRAS mutation + BRAF mutation
1m
The safety and efficacy of anti-PD-1 inhibitor-based combinational therapy in non-small cell lung cancer patients with oncogenic alterations. (PubMed, Transl Cancer Res)
The anti-PD-1 inhibitor-based combinational therapy elicited exciting anti-tumor efficacy and prolonged patient survival with manageable adverse effects in NSCLC patients harboring oncogenic alterations. The PD-L1 status and LIPI could be used as a biomarker predicting response to anti-PD-1 inhibitor-based combinational treatment in these patients.
Journal • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene)
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BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • EGFR L858R • ALK rearrangement • HER-2 exon 20 insertion • RAS mutation • RET mutation • RET rearrangement • HER-2 exon 20 mutation • EGFR L858R + EGFR exon 21 deletion • HER-2 exon 23 mutation
1m
RAS-Mutated Cytologically Indeterminate Thyroid Nodules: Prevalence of Malignancy and Behavior Under Active Surveillance. (PubMed, Thyroid)
We describe the behavior of RAS-mutant ITNs under AS and find that most demonstrate stability over time. Of the resected RAS-mutant nodules, most were benign; of the cancers, most were ATA low-risk. Immediate surgical resection of all RAS-mutant ITNs appears to be a low-value practice. Further research is needed to help define cases most appropriate for AS or immediate surgery.
Journal
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RAS (Rat Sarcoma Virus)
|
KRAS mutation • NRAS mutation • RAS mutation • HRAS mutation
1m
Molecular screening with liquid biopsy for anti-EGFR retreatment in metastatic colorectal cancer: preliminary data from the randomized phase 2 PARERE trial. (PubMed, Front Oncol)
Patients with RAS/BRAFV600E wt mCRC according to tissue genotyping who benefited from previous anti-EGFR-based treatment (fluoropyrimidines, oxaliplatin, irinotecan, and antiangiogenics) and then experienced disease progression to EGFR targeting were eligible for screening in the PARERE trial. This is the largest prospective cohort of mCRC patients screened with LB for anti-EGFR retreatment in a randomized study. ctDNA genotyping reveals that at least one out of three patients candidate for retreatment should be excluded from this therapy, and other potential drivers of anti-EGFR resistance are found in approximately one out of three patients with RAS/BRAFV600E wt ctDNA.
P2 data • Journal • Liquid biopsy • Metastases • Biopsy
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • GNAS (GNAS Complex Locus)
|
BRAF V600E • KRAS mutation • NRAS mutation • BRAF wild-type • RAS mutation • NRAS Q61 • KRAS Q61H • BRAF mutation + RAS mutation
|
oxaliplatin • irinotecan
1m
Enrollment open
|
NF1 (Neurofibromin 1) • RAS (Rat Sarcoma Virus)
|
BRAF V600E • BRAF V600K • BRAF wild-type • RAS mutation
|
Braftovi (encorafenib) • avutometinib (VS-6766) • defactinib (VS-6063)
1m
Triplet chemotherapy with or without bevacizumab as first line treatment for metastatic colorectal cancer: An AGEO multicenter real-world study. (PubMed, Dig Liver Dis)
This study highlights several factors influencing Tri-CT use +/- bevacizumab decision and confirms the real-world good oncological outcomes and tolerability of these regimens in mCRC patients. Our results suggest that Tri-CT alone may by an appropriate option for specific subgroups of patients.
Journal • Real-world evidence • Real-world • Metastases
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BRAF (B-raf proto-oncogene)
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BRAF mutation • RAS mutation
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Avastin (bevacizumab) • 5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium
1m
Comprehensive Landscape of BRAF Variant Classes, Clonalities, and Co-Mutations in Metastatic Colorectal Cancer Using ctDNA Profiling. (PubMed, Cancers (Basel))
In these patients, the high-frequency KRAS/NRAS co-mutation and its correlation with poorer prognosis underlines the urgent need for novel therapeutic strategies. This study represents one of the most comprehensive characterizations to date of atypical BRAF variants, utilizing both ctDNA and clinical cohorts.
Journal • Circulating tumor DNA • Metastases
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
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BRAF V600E • KRAS mutation • BRAF mutation • NRAS mutation • RAS mutation