A Phase Ia/b study of MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in patients with RAS mutant advanced colorectal cancer (MErCuRIC).

Background: Targeting RAS mutant (MT) colorectal cancer (CRC) remains a difficult challenge, mainly due to the pervasiveness of RAS/MEK-mediated feedback loops. Preclinical studies identified MET/STAT3 as an important mediator of resistance to KRAS-MEK1/2 blockade in RASMT CRC. This dose escalation/expansion study assessed safety and initial efficacy of the MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in RASMT advanced CRC patients.

A phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers.

Background: Single-agent MEK1/2 inhibition has been disappointing in clinical trials targeting RAS mutant (MT) cancers, probably due to upstream receptor activation, resulting in resistance. We previously found that dual c-MET/MEK1/2 inhibition attenuated RASMT colorectal cancer (CRC) xenograft growth. In this study, we assessed safety of MEK1/2 inhibitor PD-0325901 with c-MET inhibitor crizotinib and determined the optimal biological doses for subsequent clinical trials.

Cancer inequalities in the United Kingdom and the data used to measure them: a scoping review.

Significant cancer inequalities may exist across the United Kingdom (UK). Data are required to delineate and quantify these inequalities. This scoping review was undertaken to map the research evidence on UK cancer inequalities and determine the current data available, and the data gaps, that, if filled, could inform a strategy to reduce them.

Ensuring equitable and affordable access to clean water for people living with cancer in a rural and coastal setting.

Background: The UN General Assembly (UNGA) stated that the right-to-water entitles everyone to accessible and affordable water. People living with cancer (PLWC) need water for numerous reasons including hydration, personal hygiene and infection control. In 2023, reports emerged of PLWC in Lincolnshire (UK) disconnecting their water supply from cost fears.

A Comparison of International Modeling Methods for Evaluating Health Economics of Colorectal Cancer Screening: A Systematic Review.

Objectives: Cost-effectiveness analysis (CEA) is an accepted approach to evaluate cancer screening programs. CEA estimates partially depend on modeling methods and assumptions used. Understanding common practice when modeling cancer relies on complete, accessible descriptions of prior work.

Dual gene set enrichment analysis (dualGSEA); an R function that enables more robust biological discovery and pre-clinical model alignment from transcriptomics data.

Gene set enrichment analysis (GSEA) tools can identify biological insights within gene expression-based studies. Although their statistical performance has been compared, the downstream biological implications that arise when choosing between the range of pairwise or single sample forms of GSEA methods remain understudied. We compare the statistical and biological results obtained from various pre-ranking methods/options for pairwise GSEA, followed by a stand-alone comparison of GSEA, single sample GSEA (ssGSEA) and gene set variation analysis (GSVA).

Improving cancer outcomes through enhanced leadership and strategy training for cancer healthcare professionals - A course developed by the European School of Oncology (ESO), the European Cancer Organization (ECO) and Sharing Progress in Cancer Care (SPCC).

Leadership as a key building block of a health system plays a crucial role in achieving high performance and helps deliver change and shape the policy agenda and its implementation. Echoing the emerging need for effective leaders in Oncology, the "Improving Cancer Outcomes and Leadership Course" was developed jointly by the European School of Oncology (ESO), the European Cancer Organization (ECO) and Sharing Progress in Cancer Care (SPCC). The course was offered as a hybrid event online and in Warsaw in June 2022.

Empowering effective biomarker-driven precision oncology: A call to action.

Precision oncology has a significant role to play in delivering optimal patient care. Biomarkers are critical enablers for precision oncology across the continuum of cancer diagnosis, in defining patient prognosis, and in predicting the response to treatments and their potential toxicities, as well as delineating the risk of hereditary cancer syndromes. Biomarkers also potentiate cancer drug development, accelerating patient access to safe and effective therapies.

Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer.

Molecular stratification using gene-level transcriptional data has identified subtypes with distinctive genotypic and phenotypic traits, as exemplified by the consensus molecular subtypes (CMS) in colorectal cancer (CRC). Here, rather than gene-level data, we make use of gene ontology and biological activation state information for initial molecular class discovery. In doing so, we defined three pathway-derived subtypes (PDS) in CRC: PDS1 tumors, which are canonical/LGR5 stem-rich, highly proliferative and display good prognosis; PDS2 tumors, which are regenerative/ANXA1 stem-rich, with elevated stromal and immune tumor microenvironmental lineages; and PDS3 tumors, which represent a previously overlooked slow-cycling subset of tumors within CMS2 with reduced stem populations and increased differentiated lineages, particularly enterocytes and enteroendocrine cells, yet display the worst prognosis in locally advanced disease.

Skin in the game: The cost consequences of skin cancer diagnosis, treatment and care in Northern Ireland.

Background: Skin cancer is a prevalent cancer in the UK. Its rising incidence and mortality rates are expected to result in substantial financial implications, particularly on diagnostic and treatment services for skin cancer management in Northern Ireland (NI). Such anticipated disease increases underscore the need for prevention and control measures that should help guide policymaking and planning efforts.

Implementing the European code of cancer practice in rural settings.

Existing evidence often indicates higher cancer incidence and mortality rates, later diagnosis, lower screening uptake and poorer long-term survival for people living in rural compared to more urbanised areas. Despite wide inequities and variation in cancer care and outcomes across Europe, much of the scientific literature explicitly exploring the impact of rurality on cancer continues to come from Australia and North America. The European Code of Cancer Practice or "The Code" is a citizen and patient-centred statement of the most salient requirements for good clinical cancer practice and has been extensively co-produced by cancer patients, cancer professionals and patient advocates.

surviveR: a flexible shiny application for patient survival analysis.

Kaplan-Meier (KM) survival analyses based on complex patient categorization due to the burgeoning volumes of genomic, molecular and phenotypic data, are an increasingly important aspect of the biomedical researcher's toolkit. Commercial statistics and graphing packages for such analyses are functionally limited, whereas open-source tools have a high barrier-to-entry in terms of understanding of methodologies and computational expertise. We developed surviveR to address this unmet need for a survival analysis tool that can enable users with limited computational expertise to conduct routine but complex analyses.

The future of cancer care in the UK-time for a radical and sustainable National Cancer Plan.

Cancer affects one in two people in the UK and the incidence is set to increase. The UK National Health Service is facing major workforce deficits and cancer services have struggled to recover after the COVID-19 pandemic, with waiting times for cancer care becoming the worst on record. There are severe and widening disparities across the country and survival rates remain unacceptably poor for many cancers.