Volume 3 Issue 1, January 2022

A potential translational strategy to treat brain metastases is the induction or maintenance of proliferative dormancy in tumor cells. A new study shows that dormancy in breast cancer brain metastasis is maintained in the perivascular niche by astrocyte endfoot secretion of laminin-211, causing tumor cell membrane sequestration of YAP.

Although many potential targets have been identified, effective, specific therapies for metastatic cancers are still lacking. Two studies now identify small-molecule inhibitors of MTDH–SND1 interaction that potently suppress breast cancer progression and metastasis via concerted cancer-cell-autonomous effects and immune modulation.

The architecture of tumor collagen greatly influences tumor biology and therapeutic response. Two new studies identify tumor DDR1 as a central player in stromal collagen deposition and organization in the primary tumor and in disseminated tumor cells, resulting in immune exclusion or sustained dormancy, respectively.

Hwang and colleagues discuss recent advances and current challenges in developing immunotherapies for pediatric brain cancer, as well as the clinical implications of ongoing and completed studies.

Ghajar and colleagues report that astrocyte-deposited laminin-211 promotes the quiescence of disseminated tumor cells in the brain, in a manner dependent on the cytoplasmic sequestration of YAP by dystroglycan.

Kang and colleagues identify a specific compound blocking MTDH1–SND1 interaction, which prevents metastatic breast cancer progression, induces regression of established metastasis in preclinical models and restores chemosensitivity.

Kang and colleagues demonstrate that pharmacological targeting of the MTDH1–SND1 axis prevents immune evasion during metastatic progression and provides a synergistic combination strategy with immune-checkpoint blockade to treat metastasis.

Zhang and colleagues report a function of the glycolytic enzyme α-Enolase 1 in iron homeostasis. In this setting it promotes the mRNA decay of IRP1, thereby suppressing ferroptosis in hepatocellular carcinoma.

Bravo-Cordero and colleagues demonstrate that disseminated tumor cells remodel the extracellular matrix by secreting collagen III and generate a stromal architecture that favors dormancy through DDR1 and STAT1 signaling.

Zhang and colleagues analyzed patients with lung cancer treated with anti-PD-1 with single-cell methods, finding the presence of precursor exhausted T cells in responders that accumulated through local expansion and clonal revival from peripheral T cells.

Bodenmiller and colleagues present a method for three-dimensional analysis of tissue architecture using imaging mass cytometry and demonstrate the utility in resolving cellular interactions in the tumor microenvironment, in human breast cancer samples.