Breast cancer metastasis: Is it a matter of OMICS and proper ex-vivo models?

Abstract

Genomics has greatly increased the understanding of the study of breast cancer (BC) and has shaped the concept of intra-tumor heterogeneity, currently recognized as a propelling force for cancer progression. In this context, knowledge and understanding of metastatic breast cancer (mBC) has somehow lagged behind that of primary breast cancer. This may be explained by the relative scarcity of matched mBC samples, however it is possible that the mutation spectrum obtained from primary BC does not capture the full complexity of the metastatic disease. Here, we provide a few examples supporting this possibility, from public databases. We evoke the need to perform an integrated multi-OMICS characterization of mBC, to obtain a broad understanding of this complex disease, whose evolution cannot be explained solely by genomics. Pertinent to this, we suggest that rather an infrequent use of Patient-Derived -Tumor-Organoids (PDTOs) may be influenced by assuming that the metastatic conditions of PDTOs growth (mPDTOs) should be similar to those of the tissue of origin. We challenge this view by suggesting that the use of "target-organ inspired" growth conditions for mPDTOs, may better fit the emerging knowledge of metastatic disease. Thus, the integrated use of multi-OMICS and of clinically relevant mPDTOs may allow a further understanding of such disease and foster therapeutically relevant advances. We believe that our points may be valid for other solid cancers.

Keywords: Genomic; Metastatic breast cancer; Organoids; PDTO; Proteomic; multi-OMICS.

Fig. 1

Genomic alterations in metastatic breast and colorectal cancer. A. Frequency of the top 13 mutated genes in Breast Cancer (n = 918), Breast Cancer Metastases (n = 1000) and in Metastatic Breast Cancer (n = 1365). Data were retrieved from the Breast Cancer MSK databases , . B. Genomic alteration in colorectal cancer. The top 8 genomic alterations in Matched Primary and Metastatic colorectal cancer lesions (n = 14). Data derived from the Metastatic Colorectal Cancer MSK database , n = 1134 total samples. MUT: mutated; NS: not sequenced; WT: wild type.

Fig. 2

An integrative multi-OMICS approach directed at capturing the mBC complexity through the use of target tissue-directed culture conditions of PDTOs from mBC.