Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology

Patient-derived in vivo models of human cancer have become a reality, yet their turnaround time is inadequate for clinical applications. Therefore, tailored ex vivo models that faithfully recapitulate in vivo tumour biology are urgently needed. These may especially benefit the management of pancreatic ductal adenocarcinoma (PDAC), where therapy failure has been ascribed to its high cancer stem cell (CSC) content and high density of stromal cells and extracellular matrix (ECM). To date, these features are only partially reproduced ex vivo using organoid and sphere cultures. We have now developed a more comprehensive and highly tuneable ex vivo model of PDAC based on the 3D co-assembly of peptide amphiphiles (PAs) with custom ECM components (PA-ECM). These cultures maintain patient-specific transcriptional profiles and exhibit CSC functionality, including strong in vivo tumourigenicity. User-defined modification of the system enables control over niche-dependent phenotypes such as epithelial-to-mesenchymal transition and matrix deposition. Indeed, proteomic analysis of these cultures reveals improved matrisome recapitulation compared to organoids. Most importantly, patient-specific in vivo drug responses are better reproduced in self-assembled cultures than in other models. These findings support the use of tuneable self-assembling platforms in cancer research and pave the way for future precision medicine approaches.

Ovarian Cancer Tumour Biology: Genesis

Ovarian cancer (OC) is the fifth leading cause of cancer deaths among women, thus early diagnosis is of paramount importance to survival. A clear OC etiopathogenesis is not yet fully understood. Large histopathological variability predicts more initial tissue for carcinogenesis. Many connections of biologically different tissue as locus minoris resistentiae for carcinogenesis have been confirmed. Expansion of knowledge about OC etiopathogenesis may help to construct an algorithm for early diagnosis. Ovarian surface epithelium, ectopic Müllerian epithelium, and fallopian tubes, along with endometriosis, are significant in the process of OC development. An oxidative microenvironment caused by recurrent ovulation or arising due to a degradative process in ectopic endometrium, mainly endometriomas, play a prominent role in the development of OC.

Treatment of Ipsilateral Breast Cancer Recurrence (IBCR) after Breast Conservation Therapy (BCT)

In-breast recurrence or ipsilateral breast cancer recurrence (IBCR) suspected by imaging or palpation, second primary carcinoma and any distant metastases should be ruled out by core biopsy prior to breast surgery. The surgical standard in IBCR management is salvage mastectomy. Increasingly, however, patients express a justified desire for breast conservation in IBCR. In favourable relations of tumour and breast size, long interval between primary disease and IBCR recurrence, favourable tumour biology and ruled out distant metastases, re-BCT may be an option. As patients usually have undergone adjuvant radiotherapy already, re-radiotherapy (brachytherapy/percutaneous RT) should be explored. Systemic management must be based on tumour biology and prior treatment. While the risk of local recurrence increases following re-BCT, overall survival is not compromised.