The Mode of Action and Clinical Outcomes of Sacituzumab Govitecan in Solid Tumors.

Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is currently approved to treat metastatic triple-negative breast cancer and HR+/HER2- breast cancer, and is under clinical investigation for a range of other tumor types. This review describes its mode of action, development, and clinical outcomes. SG is composed of SN-38 (a topoisomerase I inhibitor derived from irinotecan) covalently linked to an anti-Trop-2 monoclonal antibody (sacituzumab; hRS7) via a hydrolysable CL2A linker.

Atypical B cell receptor signaling: straddling immune diseases and cancer.

The B-cell receptor (BCR) signaling pathway plays an essential role in the survival, proliferation, differentiation and trafficking of lymphocytic. Recent findings associate aberrant BCR signaling with specific disease pathologies, including B-cell malignancies and autoimmune disorders. Inhibition of the BCR signaling pathway may therefore provide promising new strategies for the treatment of B-cell diseases.

In this issue: Tec kinases in the crosshairs.

Tec family kinases are the second largest family of non-receptor tyrosine kinases, of critical importance to the biology of cells derived from the bone marrow. Significant progress in this area during the last decade revealed a role for several of these kinases in inflammatory and oncologic disorders. This led to the discovery and development of molecular targeted therapies against Tec kinases, most notably to date Btk, already showing promising clinical activity in B cell lymphoma and autoimmunity.

Potential for molecular targeted therapy for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma is an aggressive lymphoproliferative disorder of CD4+ T lymphocytes associated with human T-cell leukemia virus type 1 (HTLV-I) infection. Approximately 5% of infected people will develop an aggressive form of ATL, characterized by high circulating cell count, skin and organ infiltration and expression of cytokine, chemokine and survival genes. The available therapies for ATL have minimal efficacy, with few responders and poor survival.