KRAS G13

Despite the historical challenges in targeting KRAS-mutant proteins, the findings of this study support the potential of natural products as scaffolds for anticancer drug discovery as a source for developing novel anticancer therapies. The identified phytochemicals from C. officinalis such as calendasaponin D and procyanidin A2 may serve as potential leads for future preclinical and experimental validation against KRAS-driven malignancies.

This study suggests codon 13 KRAS mutations may be associated with LR in LARC. However, given the small number patients and events, these findings should be cautiously interpreted until confirmed by larger studies. Preoperative genetic testing for KRAS mutations is suggested to enhance risk stratification.

Previously, we developed small molecule ULK1 inhibitors that not only inhibit ULK kinase activity but also induced the degradation of other core members of the ULK complex including ATG101 and ATG13...Finally, immunohistochemical staining of orthotopic pancreatic tumors reveals a significant increase in CD4⁺ and CD8⁺ T cell infiltration upon treatment, suggesting that SBP-1750 enhances anti-tumor immunity. These findings support further development of SBP-1750 as a novel ATG-targeting cancer therapy.

KRASmt and NRASmt are seen in 49% and 4% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. KRASmt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.

Sensitivity to mutant-specific inhibitors largely overlapped with sensitivity to state-selective agents, suggesting that most RAS-mutant tumors will respond poorly to any currently available RAS inhibitor. Implications: Determining the signaling inhibition index (SII) can inform the design and clinical application of RAS-targeted therapies to improve tumor selectivity and therapeutic outcomes.

Here we present GoDig-LiF, which uses spectra and retention times predicted by the Prosit-TMT model in place of data libraries, enabling targeted proteomics with only a tandem mass tag-labeled sample, target list, and mass spectrometer. We applied GoDig-LiF to the quantification of mutated proteins in cancer cell lines, including KRAS G13D.

Pancreatic cancer driven by the KRASG12D mutation faces therapeutic challenges from KRAS undruggability and acquired resistance to inhibitors like MRTX1133 via secondary mutations (e.g., Q95/Y96)...In vivo, ZJK-807 (30 mg/kg, subcutaneous) achieved 47% tumor growth inhibition in AsPC-1 xenografts with favorable pharmacokinetics. This study presents a CRBN-based PROTAC to selectively target and degrade resistant KRASG12D mutants, establishing a groundbreaking approach for KRAS-driven malignancies.

Here, we found that MEK inhibitor-trametinib treatment results in the feedback activation of multiple receptor tyrosine kinases (RTKs) and that treatment with the pan-RTK inhibitor anlotinib effectively inhibits the progression of KRAS-mutant NSCLC. The phase Ib containing 20 patients demonstrated the high efficacy of this combinational therapy with RP2D, with the ORR at 65% (95% CI: 40.8-84.6), the median PFS is 11.5 months (95% CI: 8.3-15.5), the median overall survival (OS) is 15.5 months (95% CI: 15.5 to could not be evaluated), the DCR at 100% (95% CI: 83.2-100.0), the median duration of overall response (DoR) is 9.3 months (95% CI: 2.5-12.1), and the rate of AEs ≥ grade 3 at 35%. Overall, this study provides a potential combinational therapeutic strategy for KRAS-mutant NSCLC through the cotargeting of MEK and RTKs.

P1, N=45, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial primary completion date: Aug 2025 --> Jul 2026

Plasma cfDNA analysis using NGS is feasible and offers insights into alectinib resistance mechanisms. Early detection of resistance-associated mutations may guide personalized treatment strategies. Larger prospective studies are needed to validate these findings.

This study highlights the usefulness of ddPCR as a prospective clinical tool in oncology and liquid biopsy using blood cfDNA. It can be considered a better alternative to tissue biopsies and mutation profiling of candidate genes, particularly those that are linked to therapeutic response to TKIs.

In our case, it is found to have a G13D mutation in the KRAS gene and a novel RPSAP52-HMGA2 fusion. Though, the clinical significance of these alterations is yet to be proven, it may help to better understand this entity.