ERK Pathway and Response to Cetuximab-Containing Therapy
Psyrri et al. Page 3023
The selection of patients for organ preservation approaches based on risk of recurrence is of critical importance. Psyrri and colleagues used standardized, quantitative immunofluorescence to evaluate correlation between tissue biomarker expression and clinical outcome in a phase II trial of induction chemotherapy with weekly cetuximab, paclitaxel, and carboplatin followed by chemoradiation with the same regimen in operable HNSCC (E2303). Clustering analysis revealed that clusters indicative of activated RAS/MAPK/ERK and/or PI3K/Akt pathways were associated with inferior OS and/or PFS and maintained significance in multivariable analysis. These results should be validated in large prospective studies.
Driver Mutations in IDH1 Mutant Gliomas
Wakimoto et al. Page 2898
Although gliomas with isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations have a better prognosis, most eventually transform to more aggressive tumors. To identify the genetic events that drive this later malignant behavior, Wakimoto and colleagues tested patient IDH-mutant gliomas for their ability to generate orthotopic xenografts in mice. The authors found that IDH-mutant gliomas that formed xenograft in mouse brain were enriched in cancer driver mutations. In patients, presence of these driver mutations was associated with more rapid subsequent progression. Identification of recurrent, targetable driver mutations provides novel therapeutic opportunities for patients with the most refractory IDH-mutant gliomas.
Adjuvant CIK Treatment of TNBC
Pan et al. Page 3003
Triple-negative breast cancer (TNBC) is a high-risk disease but has limited treatment options because of the absence of currently identified therapeutic targets. To explore more effective therapeutic methods, Pan and colleagues retrospectively analyzed the clinical activity of sequential cytokine-induced killer cells (CIK) infusion and chemotherapy for post-mastectomy TNBC patients. The data show that additional CIK treatment significantly enhanced the disease-free survival (DFS) and overall survival (OS) rate in TNBC patients, and particularly benefited the high-risk cohort. This study represents the basis of further research into the development of optimized treatment strategies for this unique cohort of breast cancer patients.
Prognostic Impact of Specific KRAS Mutations in Colon Cancer
Yoon et al. Page 3033
Recent data suggest that KRAS mutations in codon 13 may not represent an aggressive phenotype, in contrast to codon 12 mutations. Yoon and colleagues examined the prognostic impact of the seven most common KRAS mutations in stage III colon adenocarcinomas from a large adjuvant trial. KRAS mutations, including those in codon 13 only, were associated with inferior survival compared with tumors with wild-type KRAS and BRAF. These data demonstrate the adverse prognostic impact of codon 13 mutations for the first time in nonmetastatic colon cancer and highlight the importance of mutations in both codons in the progression of this malignancy.