3D Organoids: unmasking mechanisms of resistance and accelerating precision medicine against metastatic colorectal cancer

In addition to marking the launch of World Cancer Research Day, last week´s AECC Institutional Act presided by Her Majesty Queen Leticia of Spain, also President of AECC, awarded 22 projects promising scientific excellence as well as the accelerated translation of cancer discovery at clinical level.

Allocating a total of €8 million to support these endeavors, among AECC´s awardees for 2016 is VHIO´s Guillem Argilés, Physician Scientist of VHIO´s Gastrointestinal and Endocrine Tumors Group – headed by Josep Tabernero, and Medical Oncologist at the Vall d´Hebron University Hospital (HUVH).

Fueled by AECC funding, his research will center on genotyping and screening efforts using 3D organoid models to more rapidly establish mechanisms of resistance in metastatic colorectal cancer and precisely predict sensitivity to targeted experimental therapies.

Over the last forty years mortality from colorectal cancer has risen by almost 30% and unfortunately this tumor type generally remains undetected until it reaches an advanced stage. Despite the tremendous progress made over the last decade in the diagnosis, treatment and care for cancer patients — also resulting in a transformative new model of healthcare, two of the major remaining obstacles in the collective quest to outsmart cancer are resistance to anti-cancer agents and metastatic spread.

For the majority of metastatic colorectal cancer patients current therapies ultimately cease to be effective due to the development of secondary drug resistance, with few other therapeutic options available. Identifying the mechanisms behind such resistance, as well as better predicting response to novel experimental therapies will provide fresh hope for these patients.

This AECC-funded project, under the senior direction of Elena Élez, Physician Scientist and Medical Oncologist of the same group, will focus on identifying mechanisms of acquired resistance to therapy and in so doing, seek to develop more powerful combinatorial, experimental strategies aimed at reversing resistance in patients with advanced disease.

By generating patient-derived tumor organoids from tumor biopsies, this purely translational and novel approach will more rapidly enable Guillem and co-researchers to decipher the drivers of resistance specific to each individual patient, and establish sensitivity to therapy using these models.

“Organoids are proving increasingly valuable since they faithfully recapitulate the cellular and molecular features of each patient´s cancer, as well as rapidly deliver essential insights for predicting individual drug sensitivity,”
observes Guillem Argilés, Principal Investigator of the study.

This approach could therefore represent an important forward step in more precisely selecting combinations of experimental targeted therapies matched to the specificities of each patient, each individual tumor, and significantly contribute to reversing cancer drug resistance in advanced disease.

“I am truly grateful to the Spanish Association Against Cancer for its invaluable support and backing of this timely and essential research project. Without the generous funding received from entities such as the AECC, we would not be able to pursue our determined efforts aimed at solving cancer sooner,”
he concludes.


For more information please contact: Amanda Wren, Director of Communications, Vall d´Hebron Institute of Oncology (VHIO), Tel: +34 695 207 886, Email: awren@vhio.net.


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