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1.
World J Clin Cases ; 10(9): 2818-2828, 2022 Mar 26.
Article in English | MEDLINE | ID: mdl-35434106

ABSTRACT

BACKGROUND: Primary splenic angiosarcoma (PSA) is an extremely rare and aggressive mesenchymal malignancy with high metastatic potential and a poor prognosis. There are no established treatment guidelines for PSA, even for adjuvant therapy. This rare case may provide a reliable therapeutic regime for a better prognosis. CASE SUMMARY: A 49-year-old female who complained of right-upper quadrant abdominal pain was diagnosed as having PSA with splenic rupture and liver metastasis. After splenectomy and liver tumor resection, she received sorafenib and camrelizumab therapy. After 15 mo of follow-up, she is in good condition, without recurrence or any identified metastasis. CONCLUSION: Immunotherapy combined with targeted therapy could be a potential option for the adjuvant therapy of PSA.

2.
Front Immunol ; 12: 785526, 2021.
Article in English | MEDLINE | ID: mdl-35069558

ABSTRACT

Background: MAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response. Methods: Six metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation. Results: Compared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment. Conclusions: MAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma.


Subject(s)
Immunotherapy , MAP Kinase Kinase 1 , MAP Kinase Kinase 2 , Melanoma , Humans , MAP Kinase Kinase 1/genetics , MAP Kinase Kinase 1/immunology , MAP Kinase Kinase 2/genetics , MAP Kinase Kinase 2/immunology , Melanoma/genetics , Melanoma/immunology , Melanoma/mortality , Melanoma/therapy , Mutation , Progression-Free Survival , Survival Rate
3.
World J Gastrointest Oncol ; 12(9): 1065-1072, 2020 Sep 15.
Article in English | MEDLINE | ID: mdl-33005299

ABSTRACT

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) amplification is a molecular driver for a subset of colorectal cancers (CRCs) and one of the major causes of anti-epidermal growth factor receptor (EGFR) treatment failure. Compared to dual anti-HER2 treatments, which have been shown to be effective in HER2-positive metastatic CRC patients, single-agent anti-HER2 therapy is rarely used to treat CRC. CASE SUMMARY: Herein, we report a case of RAS/BRAF-wild-type metastatic CRC that was identified as HER2-positive through circulating tumor DNA (ctDNA) testing by next-generation sequencing following the failure of two lines of therapy. Subsequently, the patient was given lapatinib monotherapy that led to a partial response with a progression-free survival of 7.9 mo. Moreover, serial ctDNA detection was used to monitor the efficacy of lapatinib. The aberration of HER2 copy number disappeared when radiographic assessment revealed a partial response. However, a high level of HER2 amplification was detected again at the time of disease progression. Finally, a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation was identified at the time of tumor progression, which may explain the acquired resistance to lapatinib. CONCLUSION: This is the first case report of HER2-positive RAS/BRAF wild-type metastatic CRC patient responding to lapatinib monotherapy. It highlights that ctDNA testing is an effective and feasible approach to evaluate the efficacy of anti-HER2 therapy.

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