Prospects of POLD1 in Human Cancers: A Review.

Cancer is the second leading cause of death globally, exceeded only by cardiovascular disease. Despite the introduction of several survival-prolonging treatment modalities, including targeted therapy and immunotherapy, the overall prognosis for the metastatic disease remains challenging. Therefore, the identification of new molecular biomarkers and therapeutic targets related to cancer diagnosis and prognosis is of paramount importance. DNA polymerase delta 1 (POLD1), a catalytic and proofreading subunit of the DNA polymerase δ complex, performs a crucial role in DNA replication and repair processes. Recently, germline and somatic mutations of the POLD1 gene have been acknowledged in several malignancies. Moreover, diversified POLD1 expression profiles have been reported in association with clinicopathological features in a variety of tumor types. With this review, we aim to summarize the current knowledge on the role of POLD1 in cancers. In addition, we discuss the future prospects and clinical applications of the assessment of POLD1 mutation and expression patterns in tumors.

Neural Component of the Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive primary malignancy of the pancreas, with a dismal prognosis and limited treatment options. It possesses a unique tumor microenvironment (TME), generating dense stroma with complex elements cross-talking with each other to promote tumor growth and progression. Diversified neural components makes for not having a full understanding of their influence on its aggressive behavior. The aim of the study was to summarize and integrate the role of nerves in the pancreatic tumor microenvironment. The role of autonomic nerve fibers on PDAC development has been recently studied, which resulted in considering the targeting of sympathetic and parasympathetic pathways as a novel treatment opportunity. Perineural invasion (PNI) is commonly found in PDAC. As the severity of the PNI correlates with a poorer prognosis, new quantification of this phenomenon, distinguishing between perineural and endoneural invasion, could feature in routine pathological examination. The concepts of cancer-related neurogenesis and axonogenesis in PDAC are understudied; so, further research in this field may be warranted. A better understanding of the interdependence between the neural component and cancer cells in the PDAC microenvironment could bring new nerve-oriented treatment options into clinical practice and improve outcomes in patients with pancreatic cancer. In this review, we aim to summarize and integrate the current state of knowledge and future challenges concerning nerve-cancer interactions in PDAC.

Conventionally fractionated radiotherapy versus CyberKnife hypofractionated radiotherapy for painful vertebral haemangiomas - A randomized clinical trial.

BACKGROUND AND PURPOSE: The outcomes of conventional radiotherapy for painful vertebral haemangiomas have been improved through dose escalation at the expense of overall treatment time. We hypothesized that with the aid of precise hypofractionated radiotherapy, it is possible to safely deliver a similar biological equivalent dose over a significantly shorter course of treatment with a comparable efficacy and safety. MATERIALS AND METHODS: In this prospective, single-institution unblinded randomized clinical trial (NCT02332408) patients with painful vertebral haemangiomas were allocated one-to-one either to 25 Gy delivered in five fractions (CK) or conventionally fractionated radiotherapy up to 36 Gy (conv.). The main endpoint was pain relief at two years, measured on a subjective and numerical scale (NRS). RESULTS: The trial was finished yielding 74 evaluable patients, including 38 in the CK arm. Adverse events were infrequent and the treatment was well tolerated. The overall treatment time was significantly shorter in the CK arm (median of 13 days vs 25 days). At two years, more than half of the patients reported improvement (46; 62.2 %) , in 21 cases the pain symptoms were stable (28.4 %), and in seven cases worse (9.5 %). There were significantly more patients reporting improvement in the CK arm (73.7 % vs 50 %; p = 0.036). The median decrease in NRS was 4 (IQR 1-5) or 59 % (IQR 20-86 %), and the difference between arms was not statistically significant. CONCLUSION: Five fractions hypofractionated radiotherapy for painful vertebral haemangiomas up to a total dose of 25 Gy is a safe treatment modality, significantly shorter compared to conventional fractionation, and possibly more effective.