Current approaches to management of bone sarcoma in adolescent and young adult patients

Abstract

Bone tumors are a group of histologically diverse diseases that occur across all ages.Two of the commonest, osteosarcoma (OS) and Ewing sarcoma (ES), are regarded as characteristic adolescent and young adult (AYA) cancers with an incidence peak in AYAs. They are curable for some but associated with unacceptably high rates of treatment failure and morbidity. The introduction of effective new therapeutics for bone sarcomas is slow, and to date, complex biology has been insufficiently characterized to allow more rapid therapeutic exploitation. This review focuses on current standards of care, recent advances that have or may soon change that standard of care and challenges to the expert clinical research community that we suggest must be met.

Novel Targeting of DNA Methyltransferase Activity Inhibits Ewing Sarcoma Cell Proliferation and Enhances Tumor Cell Sensitivity to DNA Damaging Drugs by Activating the DNA Damage Response

“…Ewing sarcoma (EWS), a malignancy of mesenchymal origin with propensity for metastasis, is the second most common primary tumor of bone and soft tissue in children and young people. Although important insights into EWS pathogenesis have emerged in recent years, EWS patient treatment is still confined to dense multidrug chemotherapy, and the prognosis of high-risk patients remains dismal, with a less than 40% of survival rate at 5 years for patients with metastatic disease at diagnosis and for those who relapse after first-line treatment ( 1 – 3 ). Thus, there is a strong demand from patients, families and physicians for additional therapies, which may derive only from further knowledge of the genetic and biological features of the tumor.…”

Sarcoma Immunotherapy: Confronting Present Hurdles and Unveiling Upcoming Opportunities

“…Chemotherapy is recommended for patients with high-grade STSs following resection, but has failed to demonstrate distinct improvements in terms of relapse-free survival or overall survival (OS) ( Squires et al, 2020 ). Although BS subtypes generally do not respond well to chemotherapy, multidrug chemotherapy has shown moderate treatment efficacy for osteosarcoma and Ewing sarcoma in combination with surgery ( Ingley et al, 2022 ). Chondrosarcoma, another common BS subtype, is generally refractory to conventional chemotherapy and radiation therapy, with no supporting efficacy data available ( Gelderblom et al, 2008 ; Monga et al, 2020 ; Riedel et al, 2009 ).…”

A New Paclitaxel Formulation Based on Secretome Isolated from Mesenchymal Stem Cells Shows a Significant Cytotoxic Effect on Osteosarcoma Cell Lines

“…Despite local tumor resection and intense chemotherapy treatment, OS is a very aggressive disease as 30–35% of patients have a local or systemic recurrence that evolves with an unfavorable prognosis: only 25% of patients survive more than five years [ 2 ]. The survival rate of patients is still lagging behind the overall survival rates of patients with other cancers in that age group, mainly due to intrinsic or acquired drug resistance [ 3 ] and the formation of lung metastases, which represent the disease’s primary cause of mortality [ 4 ]. Over the last decade, the therapeutic approach has been improved, but no innovative or efficient standardized therapy has been found to date.…”