Volume 2 Issue 7, July 2021

Institutional clinical data repositories provide a depth and consistency of data elements that is difficult to match even with data pooled from diverse sources. A study now demonstrates how real-world data and clinical encounters can be captured in an integrated ‘data story’ to enable continuous learning and hypothesis generation in oncology.

Immuno-oncology approaches have shown little efficacy against high-grade glioma, a devastating manifestation of brain cancer. A new study now finds a metabolic vulnerability in IDH1-mutant glioma that can be targeted to reprogram tumor-infiltrating macrophages and create a tumor microenvironment that is more responsive to immune-checkpoint therapy.

Pasha and Turner review recent insights into the role of intratumoral heterogeneity in therapeutic resistance in metastatic breast cancer and discuss forward-looking strategies to overcome this hurdle.

Obenauf and colleagues report that acquired resistance to BRAF and MEK inhibitors in melanoma confers cross-resistance to immune checkpoint blockade by fostering a cancer cell–instructed, immune-evasive tumor microenvironment.

Morin and colleagues develop a data-integration framework capable of performing continuous learning from electronic health records on clinical, social and demographic data collected over a decade to estimate pan-cancer survival prognosis.

Platten and colleagues find that tryptophan metabolism by myeloid cells contributes to immunosuppressive microenvironment uniquely in IDH-mutant gliomas, which can be overcome by inhibiting this pathway in murine tumor models.

Kharas and colleagues identify the RNA-binding proteins RBMX and RBMXL1 as AML tumor promoters that alter chromatin compaction and hence cell survival via transcriptional regulation of the heterochromatin protein encoded by CBX5.

Wu and colleagues develop a barcoding tool, ClonMapper, which permits single-cell lineage tracing and clonal isolation and demonstrate its utility to study clonal dynamics in human CLL cells in the context of chemotherapy treatment and resistance.