Using prognostic signatures and machine learning to identify core features associated with response to CDK4/6 inhibitor-based therapy in metastatic breast cancer.

CDK4/6 inhibitors in combination with endocrine therapy are widely used to treat HR+/HER2- metastatic breast cancer leading to improved progression-free survival (PFS) compared to single agent endocrine therapy. Over 300 patients receiving standard-of-care CDK4/6 inhibitor combination therapy for metastatic disease were enrolled at a single institution. Clinical, pathological, and gene expression data were employed to define determinants for PFS duration.

p16 expression confers sensitivity to CDK2 inhibitors.

Blocking the cell cycle is a promising avenue for cancer therapy, with Cyclin-Dependent Kinase 2 (CDK2) emerging as a key target. However, in multiple cell types, CDK4/6 activity compensates for CDK2 inhibition and sustains the proliferative program, enabling CDK2 reactivation. Thus, we hypothesized that sensitivity to CDK2 inhibition is linked to the absence of this CDK4/6-mediated compensatory mechanism.

Targeting FGFR4 Abrogates HNF1A-driven Metastasis in Pancreatic Ductal Adenocarcinoma.

Purpose: We previously identified an oncogenic role for the transcription factor HNF1A in pancreatic ductal adenocarcinoma (PDAC). However, the role of HNF1A in the metastatic progression of PDAC remains unknown and targeting modalities for HNF1A -dependent phenotypes have yet to be identified.

Experimental Design: Transwell chambers were used to assess the effects of HNF1A and FGFR4 modulation on the migration and invasion of ATCC and patient-derived PDAC cells .

Tumor Suppressors Condition Differential Responses to the Selective CDK2 Inhibitor BLU-222.

CDK2 inhibitors have recently been developed and entered clinical trials. Combination approaches can help broaden the use of therapeutic agents and establish more effective treatments. Here, we evaluated the selective CDK2 inhibitor BLU-222 for mechanisms of response in the context of ovarian and breast cancer models.

Dynamics of molecular heterogeneity in high-risk luminal breast cancer-From intrinsic to adaptive subtyping.

We evaluate therapy-induced molecular heterogeneity in longitudinal samples from high-risk, hormone-receptor positive/HER2-negative breast cancer patients with residual tumor after neoadjuvant chemotherapy from the Penelope-B trial (NCT01864746; EudraCT 2013-001040-62). Intrinsic subtypes are prognostic in pre-therapeutic (Tx) samples (n = 629, p < 0.0001) and post-Tx residual tumors (n = 782, p < 0.