Genomic studies have revealed that
breast cancer consists of a complex biological process with patient-specific genetic variations, revealing the need for individualized
cancer diagnostic testing and selection of patient-specific optimal
therapies. One of the bottlenecks in translation of genomic breakthroughs to the clinic is the lack of functional genomic assays that have high clinical translatability. Anchorage-independent three-dimensional (3D) growth assays are considered to be the gold-standard for chemosensitivity testing, and leads identified with these assays have high probability of clinical success. The
Cancer BioChip System (CBCS) allows for the simultaneous, quantitative, and real time evaluation of multitudes of anchorage-independent
breast cancer cell growth inhibitors. We employed a Test
Cancer BioChip that contains silencing RNAs (siRNAs) targeting
cancer-related genes to identify 3D-specific effectors of
breast cancer cell growth. We compared the effect of these siRNAs on colony growth of the
hormone receptor positive (MCF7) and
Human Epidermal Growth Factor Receptor 2/c- Erythroblastic
Leukemia Viral Oncogene Homolog 2 (HER2/c-erb-b2) positive (SK-BR-3) cells on the Test
Cancer BioChip. Our results confirmed cell-specific inhibition of MCF7 and SK-BR-3 colony formation by
estrogen receptor α (ESR1) and (ERBB2)
siRNA, respectively. Both cell lines were also suppressed by
Phosphoinositide-3-kinase Catalytic, alpha Polypeptide (PIK3CA)
siRNA. Interestingly, we have observed responses to
siRNA that are unique to this 3D setting. For example, ß-actin (ACTB)
siRNA suppressed colony growth in both cell types while
Cathepsin L2 (CTSL2)
siRNA caused opposite effects. These results further validate the importance of the CBCS as a tool for the identification of clinically relevant
breast cancer targets.