RESUMO
No targeted therapies are approved for non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation to date. Trametinib, a selective allosteric inhibitor of the MEK1/2, demonstrated debatable clinical activity in KRAS-mutant NSCLC. In this case, we present a recurrent advanced NSCLC with KRAS G12C mutation successfully treated with single-agent trametinib therapy. An 87-year-old man who underwent radiotherapy for the right lung adenocarcinoma was admitted to clinical oncology center for recurrent lesions in bilateral lungs. He was unwilling to perform second-line chemotherapy, but underwent molecular profiling and revealed the KRAS G12C mutation. The single-agent target therapy of trametinib showed clinical benefit without obvious toxicity. Furthermore, this report reviewed the previous date of the preclinical and clinical and summarized that KRAS G12C mutation may be more sensitive to the inhibition of mitogen-activated protein kinase kinase. This case advocates for routine screening of KRAS point mutations in the utility of precision medicine and suggests that treatment with trametinib in advanced NSCLC cases with KRAS G12C mutation is well tolerated and effective, especially for those very elderly or unsuitable for more aggressive chemotherapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/genética , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
BACKGROUND: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) has been identified as a putative cancer stem cell (CSC) marker in breast cancer. However, the clinicopathological and prognostic significance of this protein in breast cancer patients remains controversial. METHODS: This meta-analysis was conducted to address the above issues using 15 publications covering 921 ALDH1A1(+) cases and 2353 controls. The overall and subcategory analyses were performed to detect the association between ALDH1A1 expression and clinicopathological/prognostic parameters in breast cancer patients. RESULTS: The overall analysis showed that higher expression of ALDH1A1 is associated with larger tumor size, higher histological grade, greater possibility of lymph node metastasis (LNM), higher level expression of epidermal growth factor receptor 2 (HER2), and lower level expression of estrogen receptor (ER)/progesterone receptor (PR). The prognosis of breast cancer patients with ALDH1A1(+) tumors was poorer than that of the ALDH1A1(-) patients. Although the relationships between ALDH1A1 expression and some clinicopathological parameters (tumor size, LNM, and the expression of HER2) was not definitive to some degree when we performed a subcategory analysis, the predictive values of ALDH1A1 expression for histological grade and survival of breast cancer patients were significant regardless of the different cutoff values of ALDH1A1 expression, the different districts where the patients were located, the different clinical stages of the patients, the difference in antibodies used in the studies, and the surgery status. CONCLUSIONS: Our results indicate that ALDH1A1 is a biomarker to predict tumor progression and poor survival of breast cancer patients. This marker should be taken into consideration in the development of new diagnostic and therapeutic program for breast cancer.
Assuntos
Aldeído Desidrogenase/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Família Aldeído Desidrogenase 1 , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Feminino , Expressão Gênica , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Viés de Publicação , Retinal Desidrogenase , Carga TumoralRESUMO
BACKGROUND: Osimertinib is the recommended first-line treatment for adult patients with epidermal growth factor receptor (EGFR) mutation positive advanced or metastatic non-small cell lung cancer (NSCLC). However, primary or acquired resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) seems inevitable, and when drug-resistance occurs during treatment with osimertinib, the standard of care is to discontinue the TKI. CASE SUMMARY: A 57-year-old female patient with lung adenocarcinoma presented with an irritating cough accompanied by chest distress of one month duration. An enhanced head magnetic resonance imaging scan showed brain metastases. An EGFR mutation (exon 21 L858R) was detected in pleural fluid. The patient was treated with oral osimertinib (80 mg once daily) from January 2018 but developed progressive disease on December 2018. She was then successfully treated with re-challenge and tri-challenge with osimertinib (80 mg once daily) by resensitization chemotherapy twice after the occurrence of drug-resistance to osimertinib, and to date has survived for 31 mo. CONCLUSION: This case may provide some selective therapeutic options for NSCLC patients with acquired drug-resistance who were previously controlled on osimertinib treatment.