KRAS - Histology

What is KRAS?

KRAS (Kirsten rat sarcoma viral oncogene homolog) is a gene that encodes a protein belonging to the small GTPase superfamily. This protein plays a crucial role in the regulation of cell division, differentiation, and apoptosis. It is a part of the RAS/MAPK pathway, which is essential for transmitting signals from cell surface receptors to the nucleus.

Why is KRAS Important in Histology?

In histology, studying the KRAS pathway is essential because mutations in this gene are common in various cancers, including pancreatic, colorectal, and lung cancers. Understanding the histological changes associated with these mutations can help in diagnosing and developing targeted therapies.

How are KRAS Mutations Detected?

KRAS mutations are typically detected through molecular diagnostic techniques such as PCR (Polymerase Chain Reaction) and sequencing. In histological samples, these techniques can be applied to paraffin-embedded tissues, allowing for accurate mutation analysis.

What are the Histological Features of KRAS-Mutated Tumors?

Tumors with KRAS mutations often exhibit distinct histological features. For example, adenocarcinomas in the lung with KRAS mutations may show mucinous differentiation and a lepidic growth pattern. In colorectal cancer, KRAS mutations are associated with poor differentiation and a higher likelihood of metastasis.

What is the Clinical Significance of KRAS in Cancer?

KRAS mutations are prognostic and predictive biomarkers. In colorectal cancer, the presence of a KRAS mutation predicts poor response to anti-EGFR therapy. Therefore, testing for KRAS mutations is essential for guiding treatment decisions. In pancreatic cancer, KRAS mutations are almost ubiquitous, making it a critical target for drug development.

How is KRAS Targeted in Cancer Therapy?

Targeting KRAS directly has been challenging due to its high affinity for GTP/GDP and lack of suitable binding pockets. However, recent advances have led to the development of specific inhibitors like sotorasib, which targets KRAS G12C mutations. Other strategies include targeting downstream effectors in the RAS/MAPK pathway or employing combination therapies.

Future Directions in KRAS Research

Ongoing research aims to develop more effective KRAS inhibitors and to understand the mechanisms of resistance to current therapies. Additionally, novel approaches like CRISPR/Cas9 gene editing and immunotherapies are being explored to target KRAS-mutant cancers more effectively.

Relevant Publications

Molecular profile of driver genes in lung adenocarcinomas of Brazilian patients who have never smoked: implications for targeted therapies.

Issue Release: 2024

Cost-effectiveness of sotorasib as a second-line treatment for non-small cell lung cancer with KRASG mutation in China and the United States.

Issue Release: 2024

Comprehensive characterization of intraductal oncocytic papillary neoplasm (IOPN) of the pancreas: a systematic and critical review.

Issue Release: 2024

Unlocking the potential of flavonoids: Natural solutions in the fight against colon cancer.

Issue Release: 2024

Concurrent loss of LKB1 and KEAP1 enhances SHMT-mediated antioxidant defence in KRAS-mutant lung cancer.

Issue Release: 2024

Targeted sequencing of DNA/RNA combined with radiomics predicts lymph node metastasis of papillary thyroid carcinoma.

Issue Release: 2024

Impact of structural biology and the protein data bank on us fda new drug approvals of low molecular weight antineoplastic agents 2019-2023.

Issue Release: 2024

The value of ACR, European, Korean, and ATA ultrasound risk stratification systems combined with RAS mutations for detecting thyroid carcinoma in cytologically indeterminate and suspicious for malignancy thyroid nodules.

Issue Release: 2024

BI-2865, a pan-KRAS inhibitor, reverses the P-glycoprotein induced multidrug resistance in vitro and in vivo.

Issue Release: 2024

Current perspectives of KRAS in non-small cell lung cancer.

Issue Release: 2024

Stimulating macropinocytosis of peptide-drug conjugates through DNA-dependent protein kinase inhibition for treating KRAS-mutant cancer.

Issue Release: 2024

Finding the sweet spot: Targeting RAS in tumors while sparing normal tissue.

Issue Release: 2024

Emamectin benzoate-induced toxicity affects intestinal epithelial integrity involving apoptosis.

Issue Release: 2024

Injectable hybrid hydrogels enable enhanced combination chemotherapy and roused anti-tumor immunity in the synergistic treatment of pancreatic ductal adenocarcinoma.

Issue Release: 2024

Novel selective inhibitors of macropinocytosis-dependent growth in pancreatic ductal carcinoma.

Issue Release: 2024

BET-directed PROTACs in triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-436.

Issue Release: 2024

Additional impact of genetic ancestry over self-reported race/ethnicity to prevalence of KRAS mutations and allele-specific subtypes in non-small cell lung cancer.

Issue Release: 2024

Spatial iTME analysis of KRAS mutant NSCLC and immunotherapy outcome.

Issue Release: 2024

Brusatol alleviates pancreatic carcinogenesis via targeting NLRP3 in transgenic Kras Trp53 Tg (Pdx1-cre/Esr1*) #Dam mice.

Issue Release: 2024

Comparison of genomic profiling of patient-matched primary colorectal and surgical resected distant metastatic (stage IV) colorectal carcinoma for drug actionability.

Issue Release: 2024

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