Development of Novel Models of Aggressive Variants of Castration-resistant Prostate Cancer.

Background: Genomic studies have identified new subsets of aggressive prostate cancer (PCa) with poor prognosis (eg, neuroendocrine prostate cancer [NEPC], PCa with DNA damage response [DDR] alterations, or PCa resistant to androgen receptor pathway inhibitors [ARPIs]). Development of novel therapies relies on the availability of relevant preclinical models.

Objective: To develop new preclinical models (patient-derived xenograft [PDX], PDX-derived organoid [PDXO], and patient-derived organoid [PDO]) representative of the most aggressive variants of PCa and to develop a new drug evaluation strategy.

Modelling the impact of liver regeneration on hepatoblastoma patient-derived-xenograft tumor growth.

Background: Twenty percent of children with hepatoblastoma (HB) have lung metastasis at diagnosis. Treatment protocols recommend surgical removal of chemotherapy-refractory lung nodules, however no chronological order is established. As hepatectomy is followed by release of growth factors, it has been proposed that partial hepatectomy (PH) could boost local or distant residual tumor growth.

Targeting genome integrity dysfunctions impedes metastatic potency in non-small cell lung cancer circulating tumor cell-derived explants.

DNA damage and genomic instability contribute to non-small cell lung cancer (NSCLC) etiology and progression. However, their therapeutic exploitation is disappointing. CTC-derived explants (CDX) offer systems for mechanistic investigation of CTC metastatic potency and may provide rationale for biology-driven therapeutics.

STING protects breast cancer cells from intrinsic and genotoxic-induced DNA instability via a non-canonical, cell-autonomous pathway.

STING (Stimulator of Interferon Genes) is an endoplasmic reticulum-anchored adaptor of the innate immunity best known to trigger pro-inflammatory cytokine expression in response to pathogen infection. In cancer, this canonical pathway can be activated by intrinsic or drug-induced genomic instability, potentiating antitumor immune responses. Here we report that STING downregulation decreases cell survival and increases sensitivity to genotoxic treatment in a panel of breast cancer cell lines in a cell-autonomous manner.