RESUMO
The well-known proto-oncogene rearrangement during transfection (RET), also known as ret proto-oncogene Homo sapiens (human), is a rare gene that is involved in the physiological development of some organ systems and can activate various cancers, such as non-small cell lung cancer, thyroid cancer, and papillary thyroid cancer. In the past few years, cancers with RET alterations have been treated with multikinase inhibitors (MKIs). However, because of off-target effects, these MKIs have developed drug resistance and some unacceptable adverse effects. Therefore, these MKIs are limited in their clinical application. Thus, the novel highly potent and RET-specific inhibitors selpercatinib and pralsetinib have been accelerated for approval by the Food and Drug Administration (FDA), and clinical trials of TPX-0046 and zetletinib are underway. It is well tolerated and a potential therapeutic for RET-altered cancers. Thus, we will focus on current state-of-the-art therapeutics with these novel RET inhibitors and show their efficacy and safety in therapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Estados Unidos , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Lung cancer is still the leading cause of cancer-related mortality. Over the past two decades, the management of non-small cell lung cancer (NSCLC) has undergone a significant revolution. Since the first identification of activating mutations in the epidermal growth factor receptor (EGFR) gene in 2004, several genetic aberrations, such as anaplastic lymphoma kinase rearrangements (ALK), neurotrophic tropomyosin receptor kinase (NTRK) and hepatocyte growth factor receptor (MET), have been found. With the development of gene sequencing technology, the development of targeted drugs for rare mutations, such as multikinase inhibitors, has provided new strategies for treating lung cancer patients with rare mutations. Patients who harbor this type of oncologic driver might acquire a greater survival benefit from the use of targeted therapy than from the use of chemotherapy and immunotherapy. To date, more new agents and regimens can achieve satisfactory results in patients with NSCLC. In this review, we focus on recent advances and highlight the new approval of molecular targeted therapy for NSCLC patients with rare oncologic drivers.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia de Alvo Molecular , Mutação , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/genética , Antineoplásicos/uso terapêuticoRESUMO
BACKGROUND: The study aimed to analyze the relationship between the dynamic systemic immune inflammation index (SII), human papillomavirus (HPV) infection, and the prognosis of oropharyngeal cancer patients. METHOD: We retrospectively obtained the data for 131 patients treated with curative treatments and calculated their SII values based on results acquired approximately 9 months after the first treatment. The entire cohort was divided into groups according to dynamic SII and HPV infection, and their prognoses were compared. RESULTS: The high SII group, particularly the persistently high SII group, had a poor prognosis, and static SII levels cannot fully reflect the prognosis of patients with oropharyngeal cancer. In HPV- patients, unfavorable dynamic SII and the site of tumor locating at the tongue base were all significantly associated with decreased disease-free survival. In contrast, no characteristic was presented as a poor prognostic factor for disease-free or overall survival in HPV+ patients. CONCLUSION: Dynamic SII values are more comprehensive prognostic indicators for oropharyngeal cancer patients, particularly HPV- patients. It could imply that an HPV- oropharyngeal cancer patient who experienced unfavorable dynamic changes in SII should receive more frequent tests or more advanced therapies.
Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Estudos de Casos e Controles , Estudos Retrospectivos , Infecções por Papillomavirus/complicações , Fatores de Risco , Inflamação/patologia , PrognósticoRESUMO
The calibrator is one of the most important factors in the calibration of various laser 3D scanning instruments. The requirements for the diffuse reflection surface are emphasized in many national standards. In this study, spherical calibrator and plane calibrator comparative measurement experiments were carried out. The black ceramic standard sphere, white ceramic standard sphere, metal standard sphere, metal standard plane, and white ceramic standard plane were used to test the laser 3D scanner. In the spherical calibrator comparative measurement experiments, the results indicate that the RMS of the white ceramic spherical calibrator with a reflectance of approximately 60% is 10 times that of the metal spherical calibrator with the reflectance of approximately 15%, and the RMS of the black ceramic spherical calibrator with reflectance of approximately 11% is of the same order as the metal spherical calibrator. In the plane calibrators comparative measurement experiments, the RMS of the flatness measurement is 0.077 mm for the metal plane calibrator with a reflectance of 15%, and 2.915 mm for ceramic plane calibrator with a reflectance of 60%. The results show that when the optimal measurement distance and incident angle are selected, the reflectance of the calibrator has a great effect on the measurement results, regardless of the outlines or profiles. Based on the experiments, it is recommended to use the spherical calibrator or the standard plane with a reflectance of around 18% as the standard, which can obtain reasonable results. In addition, it is necessary to clearly provide the material category and surface reflectance information of the standard when calibrating the scanner according to the measurement standard.