POLE (DNA Polymerase Epsilon)

These molecular tools have the potential to change how CRC is managed by earlier detection and more precise predictive biomarkers. However, large-scale validation and clinical standardization are still crucial for their extensive utilization.

P2/3, N=260, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P2, N=197, Recruiting, Gruppo Oncologico del Nord-Ovest | N=140 --> 197

Partial response (PR) was achieved after six cycles of albumin-bound paclitaxel plus carboplatin (nab-TC) combined with bevacizumab (Bev), followed by maintenance therapy with the PARP inhibitor niraparib. This case demonstrates that Bev combined with chemotherapy may be an effective first-line regimen for this rare PTC variant. Maintenance therapy with a PARP inhibitor may prolong progression-free survival.

P=N/A, N=1500, Active, not recruiting, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Clonal evolution model indicated early POLE/POLD1 events and survival of founding clone during tumor recurrence. These findings provide valuable insights into the genomic landscape and clinical outcomes of CMMRD-associated HGGs, emphasizing the critical role of mutational signature and tumor evolution in tumorigenesis and patient prognosis.

We highlight the utility of a liquid biopsy approach to aid selection of GI cancer patients harbouring rare POLE mutations for immunotherapy, leading to complete metabolic response in addition to radiologic responses and extended survival in all three patients. This study advocates for specialised multi-disciplinary teams performing shared clinical decision making to advance personalised care and improve outcomes of a subset of GI cancer patients with a poor prognosis.

This study demonstrates a high concordance in molecular classification, histotype, tumor grade and risk group between hysteroscopic biopsy and hysterectomy specimens. These findings establish that a personalized surgical approach to EC patients can be guided by molecular classification on pre-operative biopsy.

P=N/A, N=27, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

This review evaluates the evidence supporting de-escalated therapy in carefully selected patients with POLE mutated endometrial carcinoma. We highlight the critical considerations to make effective and safe treatment decisions for patients with these tumors.

The study's findings diverge from prognostic implications of TCGA-surrogate molecular types, suggesting genetic diversity and ethnicity as potential outcome determinants in South Indian endometrial cancer patients.

POLE mutations in endometrial cancer are associated with a favorable prognosis and show promising potential for immunotherapy. Molecular subtyping that incorporates POLE mutation status should be considered standard practice for risk stratification and treatment planning.