Abstract 5725
Background
One limitation in the breast cancer research field is that there are few in vitro models of breast cancer able to predict drug response and thus clinical patients’ outcome, mainly because the present models do not take account of the tumor heterogeneity. To address this issue, we developed an in vitro 3D organoid culture system using primary human breast cancer tissue that could be used to recapitulate in vivo organs. A major difficulty in the development of such models is to identify in vitro conditions that preserve the breast cancer phenotypes observed in vivo.
Methods
We isolated organoids from breast cancer patients and optimized the organoids growing conditions. By immunofluorescence assay we confirmed the receptor status, and the preservation of epithelial (E-cadherin) or the fibroblasts components included in the tissue microenvironment (TME) (alfa-SMA and FAP). Here we used organoids as mimic of tumor burden for drug penetration studies. In particular, we studied doxorubicin (DOX) penetration and biodistribution, by several means: immunofluorescence studies, caspase assay, and cell viability.
Results
We demonstrated by IF studies, that miR-340, an oncosuppressor miR, was able to modulate DOX penetration. At the same time, miR-340 induced an increase in DOX sensitivity assessed by caspase-3 assay, PARP cleavage, as well as p38 phosphorylation. Breast cancer organoids have also been used to better understand the role of the TME in breast cancer response to therapy. We assessed drug sensitivity in the presence or absence of conditioned media obtained from cancer activated fibroblasts (CAFs). We found that organoids treated with conditioned media exhibit lower level of caspase 3 activation compared to the control upon palbociclib treatment, suggesting the importance role of TME in drug resistance.
Conclusions
Thus, organoids can be considered as a new tool for studying breast cancer and developing personalized medicine approaches and to test possible use of RNA therapeutics.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Gerolama Condorelli.
Funding
AIRC.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4883 - A New Population Model Validated Pharmacokinetic Similarity of HLX01 and Rituximab in B-Cell Lymphoma
Presenter: Yuankai Shi
Session: Poster Display session 1
Resources:
Abstract
4908 - Efficacy of salvage therapy in the treatment of Helicobacter pylori-positive gastric low-grade mucosa-associated lymphoid tissue lymphoma
Presenter: Sung-Nam Lim
Session: Poster Display session 1
Resources:
Abstract
2360 - Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing
Presenter: Seok Jae Huh
Session: Poster Display session 1
Resources:
Abstract
2430 - Clinical features, treatment and outcomes of colon and rectum mucosa-associated lymphoid tissue (MALT) lymphoma: Literature reviews published in English between 1993 and 2017
Presenter: Jeong Yeon Kim
Session: Poster Display session 1
Resources:
Abstract
4654 - Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 52 patients
Presenter: Guldane Cengiz Seval
Session: Poster Display session 1
Resources:
Abstract
1732 - Safety and efficacy of Bendamustine and Rituximab (BR) regimen in Indian Chronic Lymphocytic Leukemia patients
Presenter: Ajay Gogia
Session: Poster Display session 1
Resources:
Abstract
5784 - N-terminal B-type natriuretic peptide (NT-proBNP) as an independed prognostic marker for patients with newly diagnosed multiple myeloma complicated by dialysis-dependent renal failure
Presenter: Sergey Semochkin
Session: Poster Display session 1
Resources:
Abstract
836 - The first-line effect of Bortezomib-based Therapy on Clinical Outcomes for Taiwanese Patients with multiple myeloma
Presenter: Ching-Liang Ho
Session: Poster Display session 1
Resources:
Abstract
2085 - Impact of Donor Lymphocyte Infusion in Relapsing Myeloid Neoplasms Post Allogeneic Hematopoietic Stem Cell Transplantation
Presenter: Hanafy Hafez
Session: Poster Display session 1
Resources:
Abstract
6079 - Invasive fungal diseases in patients with Hodgkin’s lymphoma before and after allogeneic hematopoietic stem cell transplantation
Presenter: Marina Popova
Session: Poster Display session 1
Resources:
Abstract