Impact of Chemotherapeutic Stress Depends on The Nature of Breast Cancer Spheroid and Induce Behavioral Plasticity to Resistant Population

Cellular or tumor dormancy, identified recently as one of the main reasons behind post‐therapy recurrence, can be caused by diverse reasons. Chemotherapy has recently been recognized as one of such reasons. However, in‐depth studies of chemotherapy‐induced dormancy are lacking due to the absence of an in vitro human‐relevant model tailor‐made for such a scenario. This report utilized multicellular breast cancer spheroid to create a primary platform for establishing a chemotherapy‐induced dormancy model. It is observed that extreme chemotherapeutic stress affects invasive and non‐invasive spheroids differently. Non‐invasive spheroids exhibit more resilience and maintain viability and migrational ability, while invasive spheroids display heightened susceptibility and improved tumorigenic capacity. Heterogenous spheroids exhibit increased tumorigenic capacity while show minimal survival ability. Further probing of chemotherapeutically dormant spheroids is needed to understand the molecular mechanism and identify dormancy‐related markers to achieve therapeutic success in the future. The study provides a glimpse to the behavior of multicellular breast tumor spheroids against single and combined chemotherapeutic stress of extreme level. Non‐invasive spheroids resist the stress in the cost of temporary dormancy. Invasive and hetero‐culture spheroids exhibit significant cellular death but heightened clonogenic efficiency. This work will be a viable platform to study chemotherapy induced dormancy and metastatic plasticity.