Over the past 60 years,investigators of basic science,pathology,and clinical medicine have studied gastrointestinal stromal tumor(GIST) and made minor advances in patient care.Recent discoveries have led to an underst...Over the past 60 years,investigators of basic science,pathology,and clinical medicine have studied gastrointestinal stromal tumor(GIST) and made minor advances in patient care.Recent discoveries have led to an understanding of the biological role of KIT and platelet-derived growth factor receptor-α in GIST and the development of the tyrosine kinase inhibitor imatinib mesylate(Gleevec,formerly STI-571),one of the most exciting examples of targeted therapy to date.The success of targeted therapy in GIST has lead to new developments in our understanding of the medical and surgical management of the disease.Intense study of GIST may lead to new paradigms in the management of cancer.展开更多
As true for any cancer,intrinsic and acquired drug resistance represent perhaps the single biggest obstacle limiting our ability to cure patients with metastatic disease.Yet,tackling this challenge has been particular...As true for any cancer,intrinsic and acquired drug resistance represent perhaps the single biggest obstacle limiting our ability to cure patients with metastatic disease.Yet,tackling this challenge has been particularly difficult for sarcoma.First and foremost,sarcomas are rare and diverse,which splits a class of tumors representing less than 1 percent of all malignancies into more than fifty smaller molecularly and histologically distinct entities,each having its own etiology,prognosis,and clinical presentation.Even the most“common”sarcoma subtypes(e.g.,liposarcoma,leiomyosarcoma,or gastrointestinal stromal tumors)have annual incidences in the thousands in the United States,whereas rarer subtypes like desmoplastic small round cell tumors number less than fifty per year.Due to their scarcity,it’s not uncommon for just a few cell lines,organoids,or patient-derived tumor explants to exist for each sarcoma subtype.This shortage limits their usefulness to model the wide variety of innate and adaptive mechanisms that exist in human tumors.Many times,no representative preclinical model exists.The scarcity of FDA-approved drugs aimed at sarcoma-specific targets,often fusion proteins and transcription factors,is also problematic.展开更多
文摘Over the past 60 years,investigators of basic science,pathology,and clinical medicine have studied gastrointestinal stromal tumor(GIST) and made minor advances in patient care.Recent discoveries have led to an understanding of the biological role of KIT and platelet-derived growth factor receptor-α in GIST and the development of the tyrosine kinase inhibitor imatinib mesylate(Gleevec,formerly STI-571),one of the most exciting examples of targeted therapy to date.The success of targeted therapy in GIST has lead to new developments in our understanding of the medical and surgical management of the disease.Intense study of GIST may lead to new paradigms in the management of cancer.
文摘As true for any cancer,intrinsic and acquired drug resistance represent perhaps the single biggest obstacle limiting our ability to cure patients with metastatic disease.Yet,tackling this challenge has been particularly difficult for sarcoma.First and foremost,sarcomas are rare and diverse,which splits a class of tumors representing less than 1 percent of all malignancies into more than fifty smaller molecularly and histologically distinct entities,each having its own etiology,prognosis,and clinical presentation.Even the most“common”sarcoma subtypes(e.g.,liposarcoma,leiomyosarcoma,or gastrointestinal stromal tumors)have annual incidences in the thousands in the United States,whereas rarer subtypes like desmoplastic small round cell tumors number less than fifty per year.Due to their scarcity,it’s not uncommon for just a few cell lines,organoids,or patient-derived tumor explants to exist for each sarcoma subtype.This shortage limits their usefulness to model the wide variety of innate and adaptive mechanisms that exist in human tumors.Many times,no representative preclinical model exists.The scarcity of FDA-approved drugs aimed at sarcoma-specific targets,often fusion proteins and transcription factors,is also problematic.