RESUMO
Targeted therapy has shown to be a very effective treatment in tumors with specific genomic drivers. Trk has proven to be one such target. Efforts to target the Trk fusion with specific inhibitors have shown remarkable responses in a tumor agnostic fashion, with responses seen even in patients with intracranial metastasis. Entrectinib is a first-generation Trk inhibitor with impressive activity in early phase trials performed in patients with NTRK fusion positive solid tumors and ROS1 positive non-small-cell lung cancers with subsequent approval for those indications. Entrectinib was also found to be effective in treatment of brain metastasis and generally well tolerated.
Lay abstract Advances in medical science has allowed us to analyze genes within cancer cells and target abnormal genes more precisely. One such target is called NTRK, which carries genetic information and has been targeted using a medication called entrectinib. This medication is also very effective in patients with cancers that has spread to the brain. This medication can be used in any type of cancer if the cancer cells possess the abnormal DNA. Some of the side effects of entrectinib include weight gain, lightheadedness, throwing up, taste changes, swelling of legs, lack of energy and so on. Based on the benefit of entrectinib seen in clinical trials the medication was approved by the US FDA for treatment of any type of cancer with the NTRK problem. We hope that this new approach to cancer treatment will result in patients having greater benefit and live longer.
Assuntos
Benzamidas/uso terapêutico , Indazóis/uso terapêutico , Neoplasias/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Benzamidas/farmacologia , Linhagem Celular Tumoral , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Humanos , Indazóis/farmacologia , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/patologia , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Receptor trkA/antagonistas & inibidores , Receptor trkA/genética , Receptor trkB/antagonistas & inibidores , Receptor trkB/genética , Receptor trkC/antagonistas & inibidores , Receptor trkC/genéticaRESUMO
Soft tissue sarcomas are a group of rare tumors of mesenchymal origin, and account for less than 1% of all cancers. The most commonly used drug for the treatment of soft tissue sarcoma is anthracycline chemotherapeutic agent, doxorubicin. The major limitation for doxorubicin is cardiotoxicity. Hence, to overcome this limitation and to increase efficacy, aldoxorubicin was developed, which has demonstrated activity in soft tissue sarcomas without much cardiotoxicity. In this review article, we discuss mechanism of action, pharmacokinetics, preclinical studies, clinical trial data and safety profile of aldoxorubicin and its potential applicability in the future of sarcoma treatment.