Cancer heterogeneity and hierarchies

Program

Genesis of cancer

Preclinical models

Belongs to

IJC Can Ruti

Contact

OVERVIEW

Our laboratory studies the key signals governing stem cell and cell fate specification during malignant progression and the mechanisms by which different signaling pathways control cell plasticity in cancer. Specifically, we use in vivo lineage tracing, live imaging, cytometry and expression profile analysis as experimental tools to achieve our goals. Our group combines murine transgenic models, patient-derived xenografts and 3D organoids to unravel cellular hierarchies within tumors, to gain a better understanding of cancer heterogeneity and drug resistance.
 

OUR RESEARCH

Cancer is a heterogeneous disease with a cellular hierarchical organization that is largely unexplored in many tumor subtypes. Moreover, in some cases hierarchical relationships among stem cells, progenitors and differentiated cells remain unsolved due to the high degree of cellular plasticity, which allows cells to switch between different cellular stages.

 

OUR GOALS

We are a newly created group passionate about cellular hierarchies and tumor heterogeneity. Our main lines of research and specific goals are:
 
1.      To illustrate cellular hierarchies within tumors. We use a well-established hierarchical model to study multipotency in tumors. Now, we are separately monitoring three mammary epithelial compartments to measure the presence of multipotency within breast tumors. Our hypothesis is that breast tumors are indeed sustained by different subpopulations, which self-maintain independently
2.      To discover cytotoxic agents for specific cellular subpopulations. A therapy based on a combination of several drugs to target different cellular populations could eradicate primary tumors, thereby preventing relapse and metastasis. We want to screen for natural compounds that selectively kill specific subsets of cells that are responsible for tumor maintenance and/or intrinsically resistant to current therapies. 
3.      To target the tumor niche to prevent the spread of cancer. One of our main objectives is to generate in vivo tools that will allow us to study new therapeutic targets to prevent relapses in hematological cancer. To that end, our lab works on different strategies, which include murine and human models, to test a panel of drugs currently used as a standard of care for non-Hodgkin’s lymphoma (NHL) and explore the role of senescence in tumors cells, as well as in their microenvironment. 
 
Our ultimate mission is to understand the tumor heterogeneity between different patients with a view to improving their treatment of choice by searching for novel and personalized therapeutic strategies.
 

OUR CHALLENGES

We hope to answer the following questions through our research:
1.      How can cellular plasticity improve treatment for cancer patients?
2.      Can we achieve truly personalized medicine by identifying single or combinatorial therapies to target different cellular populations at the same time?
3.      Can we prevent metastasis and/or relapses by targeting the most frequently colonized tissues? 

Video

Selected Publications

Current Grants

LABAE211626RODI

Fundación científica de la asociación española contra el cáncer

BreastCan-ID Tumor heterogeneity comprehension for an improved diagnosis and treatment choice for Triple Negative Breast Cancer (TNBC)

PID2020-114647RA-I00

Ministerio de ciencia e innovación

Estudio de linajes celulares en cáncer de mama para entender las dinámicas de crecimiento tumoral y su plasticidad celular

PFERO2021.01

Fundació d'estudis i recerca oncològica

BreastCan-ID Tumor heterogeneity comprehension for an improved diagnosis and treatment choice for Triple Negative Breast Cancer (TNBC)

RYC2018-024099-I

Ministerio de ciencia, innovación y universidades

RYC2018-024099-I In vivo models to study cellular hierarchies and cancer

FJC2021-047741-I

Ministerio de ciencia e innovación

BreastCan-ID Tumor heterogeneity comprehension for an improved diagnosis and treatment choice for Triple Negative Breast Cancer (TNBC)

SLT017/20/000140

Generalitat de catalunya

BreastCan-ID Tumor heterogeneity comprehension for an improved diagnosis and treatment choice for Triple Negative Breast Cancer (TNBC)