RESUMO
Despite recent advances, prognosis of patients with advanced lung cancer remains dismal. Owing to a better understanding of the interactions between immune system and tumor cells, immunotherapy has emerged as a promising therapeutic strategy. After the recent approval of nivolumab and the promising results with other immune checkpoint inhibitors, combination strategies are now subject of intensive research. Notwithstanding these successes, immunotherapy still holds significant drawbacks. As the target shifts from tumor cells to the tumor microenvironment, treatment paradigms are changing and several improvements are needed for optimal use in clinical practice. Robust biomarkers for patient selection and a reliable way of evaluating treatment response are high priorities. Herein we review current data on immune checkpoint inhibitors for lung cancer treatment.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Imunomodulação/efeitos dos fármacos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores , Antígeno CTLA-4/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/imunologia , Humanos , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do TratamentoRESUMO
In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.
Assuntos
Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/farmacologia , Ensaios Clínicos como Assunto , Descoberta de Drogas , Receptores ErbB/antagonistas & inibidores , Humanos , Metástase Neoplásica , Assistência ao Paciente , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Melhoria de Qualidade , Receptor ErbB-2/antagonistas & inibidores , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Resultado do TratamentoRESUMO
HER2-targeted therapies have radically changed the prognosis of HER2-positive breast cancer over the last few years. However, resistance to these therapies has been a constant, leading to treatment-failure and new tumor progression. Recently, the kinase-impaired HER3 emerged as a pivotal player in oncogenic signaling, with an important role in both non-treated progression and treatment response. HER2/HER3 dimerization is required for full signaling potential and constitutes the key oncogenic unit. Also, when inhibiting PI3K/AKT pathway (as with anti-HER2 drugs) feedback mechanisms lead to a rebound in HER3 activity, which is one of the main roads to resistance. As current strategies to treat HER2-positive breast cancer are unable to inhibit this feedback response, two great promises emerged: the combination of targeted-therapies and drugs targeting HER3. In this article HER2 and HER3-targeted drugs and possible combinations between them, as well as the biomarkers to predict and monitor these drugs effect, are reviewed.