Combining causal and correlative approaches to discover biomarkers of response to paclitaxel.

We recently discovered a putative paclitaxel response predictive biomarker for glioblastoma and breast cancer using the whole genome CRISPR knockout screen. The biomarker candidate was validated in two independent breast cancer patient cohorts that received taxane treatment. To further evaluate the potential application of this biomarker in the clinic for patients with glioblastoma, a prospective validation in cohorts of patients with glioblastoma is essential and will be performed as part of our ongoing phase II clinical trial (NCT04528680). The validation of novel biomarkers of susceptibility to therapy is critical to elucidate the efficacy signal of therapeutic agents. This is especially important in the context of glioblastoma, where therapeutic benefit is variable and unpredictable, leading to negative trials, yet the outcome of subset of patients has outperformed expectations.

The possibility of cancer immune editing in gliomas. A critical review.

The relationship between anti-tumoral immunity and cancer progression is complex. Recently, immune editing has emerged as a model to explain the interplay between the immune system and the selection of genetic alterations in cancer. In this model, the immune system selects cancer cells that grow as these are fit to escape immune surveillance during tumor development. Gliomas and glioblastoma, the most aggressive and most common of all primary malignant brain tumors are genetically heterogeneous, are relatively less antigenic, and are less responsive to immunotherapy than other cancers. In this review, we provide an overview of the relationship between glioma´s immune suppressive features, anti-tumoral immunity and cancer genomics. In this context, we provide a critical discussion of evidence suggestive of immune editing in this disease and discuss possible alternative explanations for these findings.