Highlights of This Issue

Abstract

Treatment options for triple negative breast cancer (TNBC) patients are limited in scope and effectiveness, particularly in the metastatic setting. Proia and colleagues show that the TNBC phenotype is highly sensitive to the pleiotropic effects of HSP90 inhibition using the investigational drug ganetespib. Ganetespib simultaneously deactivated multiple oncogenic pathways in TNBC cells, suppressed lung metastasis in mouse models, and potentiated the antitumor activity of standard-of-care TNBC chemotherapeutics in vitro and in tumor xenografts. Shrinkage of metastatic lung and lymphatic lesions were observed in patients undergoing ganetespib monotherapy. These findings support the continued exploration of ganetespib for the clinical management of TNBC.Little is known about T-cell responses against advanced epithelial cancers. By establishing new cancer cell lines and expanding tumor-infiltrating lymphocytes from the same patients, Turcotte and colleagues provide evidence at the clonal and molecular level that naturally occurring CD8+ T cells can exhibit tumor specificity against gastrointestinal cancer metastases. This observation represents a rational basis for the development of T cell-based treatments for patients with these malignancies, which will have to take into account the low frequency of tumor-reactive T cells, the absence of shared antigen recognition across allogeneic tumors, and the heterogeneity in antigen expression by tumors.Ductal carcinoma in-situ (DCIS) is the main precursor of invasive breast cancer and accounts for 25–30% of all breast cancers. Only half will progress to invasive disease during a woman's lifetime, but currently there are no markers for predicting which patients might progress. Allen et al demonstrate that tumor-suppressive myoepithelial cells are altered in a subset of DCIS through up-regulation of integrin αϖβ6 and is significantly associated with recurrence and progression. In-vivo and In-vitro expression of αϖβ6 in myoepithelial cells enhances tumor growth and invasion. This suggests that myoepithelial αϖβ6 may be of prognostic importance and help stratify patient care.Antiangiogenic treatments that target pathways other than VEGF have the potential to treat patients who have progressed despite anti-VEGF therapy and to improve outcomes when used in combination with VEGF-directed therapies. Bendell and colleagues describe the phase I clinical evaluation of dalantercept, a receptor fusion protein that inhibits BMP9/BMP10/ALK1 signaling, in adults with advanced solid tumors. Dalantercept exhibited a safety profile distinct from that of VEGF inhibitors and displayed multiple signs of antitumor activity, including a partial response, long-term stable disease, and correlative pharmacodynamic activity assessed by functional imaging. The BMP9/BMP10/ALK1 pathway is a promising target for antiangiogenic cancer therapy.