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.
