Antibody-Drug Conjugates and Their Potential in the Treatment of Patients with Biliary Tract Cancer.

Biliary tract cancers (BTCs) are aggressive in nature, often presenting asymptomatically until they are diagnosed at an advanced stage. Surgical resection or liver transplantation are potential curative options. However, a large proportion of patients present with incurable locally advanced or metastatic disease and most of these patients are only eligible for palliative chemotherapy or best supportive care.

Functional Characterisation of the ATOH1 Molecular Subtype Indicates a Pro-Metastatic Role in Small Cell Lung Cancer.

Molecular subtypes of Small Cell Lung Cancer (SCLC) have been described based on differential expression of transcription factors (TFs) , and immune-related genes. We previously reported an additional subtype based on expression of the neurogenic TF within our SCLC Circulating tumour cell-Derived eXplant (CDX) model biobank. Here we show that ATOH1 protein was detected in 7/81 preclinical models and 16/102 clinical samples of SCLC.

Current Evidence for Immune Checkpoint Inhibition in Advanced Hepatocellular Carcinoma.

The treatment of advanced unresectable HCC (aHCC) remains a clinical challenge, with limited therapeutic options and poor prognosis. The results of IMbrave150 and HIMALAYA have changed the treatment paradigm for HCC and established immune checkpoint inhibition (ICI), either combined with anti-angiogenic therapy or dual ICI, as preferred first-line therapy for eligible patients with aHCC. Numerous other combination regimens involving ICI are under investigation with the aim of improving the tumour response and survival of patients with all stages of HCC.

The AGAMENON-SEOM model for prediction of survival in patients with advanced HER2-positive oesophagogastric adenocarcinoma receiving first-line trastuzumab-based therapy.

Background: Trastuzumab and chemotherapy is the standard first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastro-oesophageal cancer. The objective was to develop a predictive model for overall survival (OS) and progression-free survival (PFS) in patients treated with trastuzumab.

Methods: Patients with HER2-positive advanced gastro-oesophageal adenocarcinoma (AGA) from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry and treated first line with trastuzumab and chemotherapy between 2008 and 2021 were included.

cfDNA methylome profiling for detection and subtyping of small cell lung cancers.

Small cell lung cancer (SCLC) is characterized by morphologic, epigenetic and transcriptomic heterogeneity. Subtypes based upon predominant transcription factor expression have been defined that, in mouse models and cell lines, exhibit potential differential therapeutic vulnerabilities, with epigenetically distinct SCLC subtypes also described. The clinical relevance of these subtypes is unclear, due in part to challenges in obtaining tumor biopsies for reliable profiling.

EPAC-lung: European pooled analysis of the prognostic value of circulating tumour cells in small cell lung cancer.

Background: Circulating tumour cell (CTC) number is an independent prognostic factor in patients with small cell lung cancer (SCLC) but there is no consensus on the CTC threshold for prognostic significance. We undertook a pooled analysis of individual patient data to clinically validate CTC enumeration and threshold for prognostication.

Methods: Four European cancer centres, experienced in CellSearch CTC enumeration for SCLC provided pseudo anonymised data for patients who had undergone pre-treatment CTC count.

Profiling of Circulating Free DNA Using Targeted and Genome-wide Sequencing in Patients with SCLC.

Introduction: SCLC accounts for approximately 250,000 deaths worldwide each year. Acquisition of adequate tumor biopsy samples is challenging, and liquid biopsies present an alternative option for patient stratification and response monitoring.

Methods: We applied whole genome next-generation sequencing to circulating free DNA (cfDNA) from 39 patients with limited-stage (LS) SCLC and 30 patients with extensive-stage SCLC to establish genome-wide copy number aberrations and also performed targeted mutation analysis of 110 SCLC associated genes.

Targeting DNA damage in SCLC.

SCLC accounts for 15% of lung cancer worldwide. Characterised by early dissemination and rapid development of chemo-resistant disease, less than 5% of patients survive 5 years. Despite 3 decades of clinical trials there has been no change to the standard platinum and etoposide regimen for first line treatment developed in the 1970's.

The clinical utility of circulating tumour cells in patients with small cell lung cancer.

Small cell lung cancer (SCLC) accounts for 15% of lung cancer diagnosed worldwide. It is aggressive and characterised by early metastatic spread with rapid development of chemo resistance such that less than 5% of patients diagnosed survive 5 years. Surgery is rarely performed and failure to identify new effective treatments has been attributed in a large part to lack of good quality tumour biopsies available for translational research.