Clinical and molecular features of early onset pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PDAC) is a major health burden and may become the second cause of death by cancer in developed countries. The incidence of early-onset pancreatic cancer (EOPC, defined by an age at diagnosis <50 years old) is increasing. Here, we conducted a study of all PDAC patients followed at our institution.

Role of molecular biology in the management of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in patient management due to a dismal prognosis, increasing incidence, and limited treatment options. In this regard, precision medicine, which personalizes treatments based on tumour molecular characteristics, has gained great interest. However, its widespread implementation is not fully endorsed in current recommendations.

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.

Precision medicine for KRAS wild-type pancreatic adenocarcinomas.

Background: KRAS mutation is the most common molecular alteration in pancreatic adenocarcinoma (PDAC), and around 10% of patients harbor KRAS wild-type tumors (KRAS).

Methods: A retrospective chart review of clinical/molecular data was performed including all PDAC patients with a determined KRAS status (tumor molecular profiling on tissue or liquid biopsy).

Results: 342 patients were included with 54 KRAS PDAC (16%) compared to 288 patients with KRAS PDAC.

Precision Medicine in Pancreatic Ductal Adenocarcinoma: The Impact of Targeted Therapies on Survival of Patients Harboring Actionable Mutations.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC, some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and improved outcomes.

Targetable Molecular Alterations in the Treatment of Biliary Tract Cancers: An Overview of the Available Treatments.

Biliary tract cancers (BTCs) are rare tumours, most often diagnosed at an unresectable stage, associated with poor prognosis, with a 5-year survival rate not exceeding 10%. Only first- and second-line treatments are well codified with the combination of cisplatin-gemcitabine chemotherapy and immunotherapy followed by 5-FU and oxaliplatin chemotherapy, respectively. Many studies have shown that BTC, and more particularly intrahepatic cholangiocarcinoma (iCCA), have a high rate of targetable somatic alteration.

Prognostic Value of the Lung Immune Prognosis Index Score for Patients Treated with Immune Checkpoint Inhibitors for Advanced or Metastatic Urinary Tract Carcinoma.

Few prognostic factors have been identified in patients with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). The Lung Immune Prognostic Index (LIPI) was associated with clinical outcomes for ICIs in several tumor types. We aim to assess the value of the LIPI in patients with mUC treated with ICIs.

Intra-arterial hepatic bevacizumab and systemic chemotherapy in hepatic metastasis of colorectal cancer: A phase II multicentric trial in second-line treatment.

Introduction: Intra-arterial hepatic (IAH) treatment has shown promising results in the management of patients with unresectable colorectal liver metastases (CRLM) the prognosis of which is poor. Bevacizumab adjunction to standard chemotherapy has been shown to improve survival of this patient population. This prospective study was conducted to assess the efficacy and safety of IAH bevacizumab combined to systemic chemotherapy after first-line treatment failure in patients with CRLM.

Immunotherapy and Hepatocellular Cancer: Where Are We Now?

Immunotherapy has demonstrated its effectiveness in many cancers. In hepatocellular carcinoma (HCC), promising results shown in the first phase II studies evaluating anti-PD-1 or anti-PD-L1 monotherapies resulted in their approval in the United States. Approval was not obtained in Europe; subsequent randomized studies in first- or second-line treatment did not confirm these initial results.

PARP Inhibition, a New Therapeutic Avenue in Patients with Prostate Cancer.

Up to 25% of patients with metastatic prostate cancer present with germline or somatic DNA damage repair alterations, some of which are associated with aggressive disease and poor outcomes. New data have brought poly(ADP-ribose) polymerase (PARP) inhibitors into sharp focus in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Olaparib improved survival after at least one new hormonal therapy (NHT) in a cohort of patients harboring BRCA1, BRCA2 or ATM mutations in the PROfound trial, while rucaparib, talazoparib and niraparib demonstrated compelling activity in phase II trials.

Next-generation androgen receptor inhibitors in non-metastatic castration-resistant prostate cancer.

Until recently, continuing androgen deprivation therapy (ADT) and closely monitoring patients until evolution towards metastatic castration-resistant prostate cancer (CRPC) were recommended in men with non-metastatic CRPC (nmCRPC). Because delaying the development of metastases and symptoms in these patients is a major issue, several trials have investigated next-generation androgen receptor (AR) axis inhibitors such as apalutamide, darolutamide, and enzalutamide in this setting. This review summarizes the recent advances in the management of nmCRPC, highlighting the favourable impact of next-generation AR inhibitors on metastases-free survival, overall survival and other clinically meaningful endpoints.

Efficacy of histology-agnostic and molecularly-driven HER2 inhibitors for refractory cancers.

A targeted therapy is recommended in case of alteration for breast and gastric carcinomas, but miscellaneous other tumor types are altered at low prevalence. Broadening the administration of HER2 inhibitors across tumor types and genomic alterations could benefit to patients with refractory metastatic tumors. Targeted next-generation-sequencing (tNGS) and comparative genomic hybridization array (CGH) have been performed on fresh tumor biopsies of patients included in the MOSCATO-01 and ongoing MOSCATO-02 trials to administrate HER2 inhibitors in case of pathogenic mutation of amplification.

Early PSA response is an independent prognostic factor in patients with metastatic castration-resistant prostate cancer treated with next-generation androgen pathway inhibitors.

Background: The optimal use of new therapies in metastatic castration-resistant prostate cancer (mCRPC) remains to be clarified. Prostate-specific antigen (PSA) response used as a pharmacodynamic end-point may help identify patients with early resistance to new androgen receptor-pathway inhibitors. We aimed to determine the clinical significance of early PSA response (EPR) during therapy with enzalutamide, abiraterone acetate (AA) and orteronel in mCRPC.