bims-myxlip 2023-04-09 papers

Issue of 2023–04–09
two papers selected by
Laura Mannarino, Humanitas Research

Front Oncol. 2023 ;13 1150765

New therapeutics for soft tissue sarcomas: Overview of current immunotherapy and future directions of soft tissue sarcomas.

Gyuhee Seong, Sandra P D'Angelo.

Soft tissue sarcoma is a rare and aggressive disease with a 40 to 50% metastasis rate. The limited efficacy of traditional approaches with surgery, radiation, and chemotherapy has prompted research in novel immunotherapy for soft tissue sarcoma. Immune checkpoint inhibitors such as anti-CTLA-4 and PD-1 therapies in STS have demonstrated histologic-specific responses. Some combinations of immunotherapy with chemotherapy, TKI, and radiation were effective. STS is considered a 'cold', non-inflamed tumor. Adoptive cell therapies are actively investigated in STS to enhance immune response. Genetically modified T-cell receptor therapy targeting cancer testis antigens such as NY-ESO-1 and MAGE-A4 demonstrated durable responses, especially in synovial sarcoma. Two early HER2-CAR T-cell trials have achieved stable disease in some patients. In the future, CAR-T cell therapies will find more specific targets in STS with a reliable response. Early recognition of T-cell induced cytokine release syndrome is crucial, which can be alleviated by immunosuppression such as steroids. Further understanding of the immune subtypes and biomarkers will promote the advancement of soft tissue sarcoma treatment.

Keywords: T-cell receptor therapy; adoptive immunotherapy; cancer testis antigen; chimeric antigen receptor (CAR) T-cell; immune checkpoint inhibitor; soft tissue sarcoma; tumor microenvironment; tumor-infiltrating lymphocyte

DOI: https://doi.org/10.3389/fonc.2023.1150765

Expert Rev Anticancer Ther. 2023 Apr 05.

Emerging predictive biomarkers in the management of bone and soft tissue sarcomas.

Candace L Haddox, Richard F Riedel.

INTRODUCTION: Soft tissue and bone sarcomas are a heterogeneous group of malignancies, each with a unique biology and clinical course. As our understanding of individual sarcoma subtypes and their molecular landscapes increases, predictive biomarkers are emerging to improve patient selection for chemotherapies, targeted therapies, and immunotherapy approaches.
AREAS COVERED: This review highlights predictive biomarkers rooted in molecular mechanisms of sarcoma biology, focusing on cell cycle regulation, DNA damage repair, and immune microenvironment interactions. We review CDK4/6 inhibitor predictive biomarkers, including CDKN2A loss, ATRX status, MDM2 levels, and Rb1 status. We discuss homologous recombination deficiency (HRD) biomarkers that predict vulnerability to DNA damage repair (DDR) pathway inhibitors, such as molecular signatures and functional HRD markers. We describe tertiary lymphoid structures and suppressive myeloid cells in the sarcoma immune microenvironment that may influence immunotherapy efficacy.
EXPERT OPINION: While predictive biomarkers are not routinely used in sarcoma clinical practice currently, emerging biomarkers are being developed alongside clinical advancements. Novel therapies and predictive biomarkers will be essential for individualizing future approaches to sarcoma management and improving patient outcomes.

Keywords: DNA damage repair; cell cycle control; homologous recombination; immune microenvironment; predictive biomarkers; sarcoma

DOI: https://doi.org/10.1080/14737140.2023.2200169