The Worldwide Innovative Networking (WIN) Consortium in personalized cancer medicine was initiated in 2010 with leadership from leading cancer centers worldwide. WIN is a non-profit, non-governmental organization headquartered in Paris.

WIN was created to accelerate the pace and reduce the cost of translating novel cancer treatments to the bedside by developing and applying, through worldwide clinical trials and research projects, the most promising advances in genomic-based cancer research. WIN aims to initiate research projects each year in a global consortium guided by an independent scientific advisory board.

WIN now includes 32 institutional members. These stakeholders have come together from all parts of the world to address the challenge of increasing the efficacy of cancer diagnostics and therapeutics by understanding the genetics and biology of each individual’s tumor and accounting for genetic differences across diverse populations—from North and South America, Europe, Asia, Middle East and Australia.

Our goal is to significantly improve outcomes for patients around the globe. We aim to increase the number of patients worldwide that have access to innovative, global clinical trials in the area of genomic-based cancer therapeutics. Global diversity and inclusion of all stakeholders is WIN’s most important and differentiating asset.

WIN enables cross-sector collaborations designed to accelerate the speed and efficacy with which breakthroughs in personalized cancer medicine can be realized and brought to patients worldwide.

Our members include leading academic, pharmaceutical, life science, not-for-profit, health, patient advocacy and IT organizations.

The response to a genetically-targeted therapy can vary due to differences in ethnicity and environment. WIN's global studies are designed to identify and account for this variability, enhancing the speed and efficacy with which novel discoveries can be made and brought to patients around the world.

WIN Symposia, held annually, brings together hundreds of leaders representing all stakeholders from around the world in a forum designed to promote the exchange of ideas and information.

WIN's article “Digital Display Precision Predictor: the prototype of a global biomarker model to guide treatments with targeted therapy and predict progression-free survival” published by NPJ Precision Oncology, a Nature Research journal.

The WIN SPRING trial was conducted in the USA, France, Spain, Luxembourg and Israel in the following cancer centers: University of California - San Diego's Moores Cancer Center, Avera Cancer Center (Sioux Falls, Arizona), Institut Curie (Paris), Centre Léon Bérard (Lyon), Vall d'Hebron Institute of Oncology (Barcelona), Centre Hospitalier de Luxembourg (Luxembourg), and Chaim Sheba Medical Center (Israel).

The trial was sponsored by the WIN Consortium and funded by ARC Fondation for cancer research (France). The drugs were donated by Pfizer Inc.

Published in Nature Medicine, results of WINTHER, the first study pioneered by the WIN Consortium.

Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial - shows that RNA profiling together with DNA testing matches more patients with advanced cancer to personalized therapies than DNA profiling for tumor mutations alone.

European funded trials WINTHER EU FP7 funded and CHEMORES EU FP6 funded established foundations for WIN future global strategy for lung cancer currently under development.

The concept underlying the new strategy is developed in the following publications:

Therapeutic Advances in Medical Oncology
March 31, 2023

Abstract
Background:
The current model of clinical drug development in oncology displays major limitations due to a high attrition rate in patient enrollment in early phase trials and a high failure rate of drugs in phase III studies.

Objective:
Integrating transcriptomics for selection of patients has the potential to achieve enhanced speed and efficacy of precision oncology trials for any targeted therapies or immunotherapies.

Methods:
Relative gene expression level in the metastasis and normal organ-matched tissues from the WINTHER database was used to estimate in silico the potential clinical benefit of specific treatments in a variety of metastatic solid tumors.

Results:
As example, high mRNA expression in tumor tissue compared to analogous normal tissue of c-MET and its ligand HGF correlated in silico with shorter overall survival (OS;p < 0.0001) and may constitute an independent prognostic marker for outcome of patients with metastatic solid tumors, suggesting a strategy to identify patients most likely to benefit from MET-targeted treatments. The prognostic value of gene expression of several immune therapy targets (PD-L1, CTLA4, TIM3, TIGIT, LAG3, TLR4) was investigated in non-small-cell lung cancers and colorectal cancers (CRCs) and may be useful to optimize the development of their inhibitors, and opening new avenues such as use of anti-TLR4 in treatment of patients with metastatic CRC.

Conclusion:
This in silico approach is expected to dramatically decrease the attrition of patient enrollment and to simultaneously increase the speed and detection of early signs of efficacy. The model may significantly contribute to lower toxicities. Altogether, our model aims to overcome the limits of current approaches.

Keywords: analogous normal tissue biopsies, clinical trials, oncology, transcriptomics, tumor biopsies

View the full article here: Download pdf

https://youtu.be/Uxicpg6Fb98

SAGE Journals: Therapeutic Advances in Medical Oncology:
October 3, 2022

Abstract:
Background: SARS-CoV-2 (COVID-19) elicits a T-cell antigen-mediated immune response of variable efficacy. To understand this variability, we explored transcriptomic expression of angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) and of immunoregulatory genes in normal lung tissues from patients with non-small cell lung cancer (NSCLC).

Methods:
This study used the transcriptomic and the clinical data for NSCLC patients generated during the CHEMORES study [n = 123 primary resected (early-stage) NSCLC] and the WINTHER clinical trial (n = 32 metastatic NSCLC).

Results:
We identified patient subgroups with high and low ACE2 expression (p = 1.55 × 10−19) in normal lung tissue, presumed to be at higher and lower risk, respectively, of developing severe COVID-19 should they become infected. ACE2 transcript expression in normal lung tissues (but not in tumor tissue) of patients with NSCLC was higher in individuals with more advanced disease. High-ACE2 expressors had significantly higher levels of CD8+ cytotoxic T lymphocytes and natural killer cells but with presumably impaired function by high Thymocyte Selection-Associated High Mobility Group Box Protein TOX (TOX) expression. In addition, immune checkpoint-related molecules – PD-L1, CTLA-4, PD-1, and TIGIT – are more highly expressed in normal (but not tumor) lung tissues; these molecules might dampen immune response to either viruses or cancer. Importantly, however, high inducible T-cell co-stimulator (ICOS), which can amplify immune and cytokine reactivity, significantly correlated with high ACE2 expression in univariable analysis of normal lung (but not lung tumor tissue).

Conclusions:
We report a normal lung immune-tolerant state that may explain a potential comorbidity risk between two diseases – NSCLC and susceptibility to COVID-19 pneumonia.

Further, a NSCLC patient subgroup has normal lung tissue expressing high ACE2 and high ICOS transcripts, the latter potentially promoting a hyperimmune response, and possibly leading to severe COVID-19 pulmonary compromise.

Keywords: ACE2 expression, cancer, COVID-19, normal lung, transcriptomics

View the full article here: Download pdf

Ther Adv Med Oncol
2022, Vol.14:1-15
DOI: 10.1177/
17588359221133893
Article reuse guidelines: sagepub.com/journals-permissions

September 20, 2022

https://www.youtube.com/watch?v=1sXMWuoZbI0