KRAS G12

P2, N=13, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=27 --> 13

E/M-CTC ≤ 1 showed a trend toward improved OS (p = 0.086). In addition, patients with > 1 CTC who received local radiotherapy for progressive lesions after glecirasib targeted therapy had significantly prolonged PFS and OS compared to those who did not (p < 0.05).

Experimentally, KRASQ61R mutation led to KRAS exon 3 skipping, which in turn could be rescued by expression of U2AF1I24T. Our findings provide evidence that splicing factor mutations can rescue splicing defects caused by oncogenic mutations in a dynamic process of cascading selection.

P2, N=19, Active, not recruiting, Georgetown University | Recruiting --> Active, not recruiting | N=54 --> 19

In localized PDAC, KRAS-mutant ctDNA detected by NGS or ddPCR was associated with worse survival. ddPCR identified additional patients missed by NGS. Integrating ddPCR with NGS ctDNA measures may improve perioperative risk stratification, though validation is needed before clinical implementation.

The SCLC component dictated adjuvant cisplatin-etoposide regardless of the accompanying adenocarcinoma histology. This case report exemplifies the importance of integrated histologic and molecular evaluation, and the need to recognize potentially actionable mutations in combined SCLC. Comprehensive profiling not only clarifies clonal relationships and may guide therapeutic strategies, including in the context of recurrence or combined presentations.

P1/2, N=713, Completed, Amgen | Active, not recruiting --> Completed

Despite apparently favorable pathological staging and adjuvant FOLFIRINOX chemotherapy, the patient developed early biochemical progression with rapidly rising carbohydrate antigen 19-9 (CA 19-9) levels, followed by widespread metastatic dissemination involving the liver, lung, spine, skeletal muscle, and multiple visceral sites...This case highlights the limitations of anatomical staging in PDAC and emphasizes the prognostic importance of tumor biology, including KRAS mutation status, lymphovascular invasion, and perineural invasion. It also demonstrates the potential limitations of CA 19-9 as a solitary marker of treatment response in biologically aggressive disease.

Using a paclitaxel (PTX)-resistant Lewis lung carcinoma cell line, we demonstrated that ERK-dependent Pgp1 functions as a shared upstream regulator of both chemoresistance and metastatic competence...Importantly, meta-analysis of clinical datasets further linked co-elevated FN and Pgp1 expression with poor prognosis and relapse in early-stage cancer patients, underscoring the translational relevance of targeting this shared pathway. These findings identify Mul A as a promising non-cytotoxic therapeutic candidate and elucidate the shared upstream molecular mechanism linking distinct downstream chemoresistance and metastasis.

TCRs that recognize the KRAS hotspot shared sequence motifs were found in several lung cancer patients. Our study highlights the successful generation of multi-valent KRAS-specific TCRs and supports the feasibility of targeting shared KRAS neoantigens through TCR engineering in lung cancer.

Subsequently, molecular dynamics (MD) simulation and MM-GBSA calculations rationalized its postulated binding towards KRAS G12D. This study provides an example of how to conduct an in-depth benchmarking approach for KRAS G12D and offering an evaluated SBVS protocol for it.

Functional analysis demonstrated increased sensitivity of AZACL2 cells to the BRAF inhibitor dabrafenib and MEK inhibitors including trametinib, compared with BRAF wild-type cell lines. The mutation spectrum was broadly consistent with previous reports, suggesting a conserved molecular landscape across geographic regions. Collectively, these data identify BRAF and HER2 alterations as clinically relevant candidates for molecular diagnostics and targeted therapy in canine pulmonary adenocarcinoma.