RESUMO
The transforming growth factor-beta (TGF-ß) signaling pathway has been reported to be dysregulated in the pathogenesis of several malignancies, including gynecologic cancers. This provides proof of concept of its potential value as a therapeutic target and prognostic biomarker in cervical cancer. Here we provide an overview of the biological role and clinical impact of TGF-ß inhibitors either as a single agent or as a combinatorial therapy in gynecological cancers, concentrating on phase I to phase II/III clinical trials. Aberrant TGF-ß signaling may lead to carcinogenesis. Inhibition of TGF-ß represents an interesting area of focus for the treatment of gynecological cancer. Several TGF-ß inhibitors are potential anticancer agents and are undergoing clinical trials in cancer, including galunisertib, dalantercept, and vigil. There is a growing body of data showing the potential therapeutic impact of targeting the TGF-ß pathway in different cancer types, although further studies are still warranted to explore the value of this strategy and finding the most appropriate patients who could most benefit from therapy.
Assuntos
Antineoplásicos , Neoplasias dos Genitais Femininos , Humanos , Feminino , Antineoplásicos/farmacologia , Transdução de Sinais , Neoplasias dos Genitais Femininos/tratamento farmacológico , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fatores de Crescimento Transformadores/farmacologiaRESUMO
Pancreatic cancer is among the most lethal malignancies with poor prognosis and patients become chemoresistant to current therapies, supporting further investigations to identify new therapeutic regimens in the treatment of this condition. Preclinical and clinical studies now appear to support the role of the renin-angiotensin system (RAS) in the regulation of tumor growth, angiogenesis, and metastasis in different malignancies including pancreatic cancer. These studies suggest that RAS blockers; Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs); could have anti-carcinogenic effects and improve clinical outcomes in the management of pancreatic cancer. Here we provided an overview of ACE inhibitors and ARBs as a potential therapeutic option in the treatment of pancreatic cancer.
Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Quimioterapia Combinada , Humanos , Hipertensão/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacosRESUMO
Gastrointestinal (GIs) cancers are among the most common causes of cancer related death, and hence the importance for the identification of novel prognostic/predictive biomarkers for detection of patients at an early stage, and for using these to identify novel targeted therapies to improve the efficacy of existing chemotherapeutic regimens. Programmed cell death 1 has been reported as a potential target in several malignancies, and targeting agents are being developed, some already approved by FDA, such as: pembrolizumab, Atezolizumab, Nivolumab. Pembrolizumab that have been approved for the treatment of metastatic non-small cell lung cancer. Here we provide an overview of the mechanism of action PD-1/PD-L1, prognostic value and current progress in clinical trials using PD-1/PD-L1 inhibitors, and the resistant mechanisms at underlie the inhibitory effect of these agents in the treatment of gastrointestinal cancers.
