Therapeutic resistance and cancer recurrence mechanisms: Unfolding the story of tumour coming back

Cancer recurrence is believed to be one of the major reasons for the failure of cancer treatment strategies. This biological phenomenon could arise from the incomplete eradication of tumour cells after chemo-and radiotherapy. Recent developments in the design of models reflecting cancer recurrence and in vivo imaging techniques have led researchers to gain a deeper and more detailed insight into the mechanisms underlying tumour relapse. Here, we provide an overview of three important drivers of recurrence including cancer stem cells (CSCs), neosis, and phoenix rising. The survival of cancer stem cells is well recognized as one of the primary causes of therapeutic resistance in malignant cells. CSCs have a relatively latent metabolism and show resistance to therapeutic agents through a variety of routes. Neosis has proven to be as an important mechanism behind tumour self-proliferation after treatment which gives rise to the expansion of tumour cells in the injured site via production of Raju cells. Phoenix rising is a pro-recurrence pathway through which apoptotic cancer cells send strong signals to the neighbouring diseased cells leading to their multiplication. The mechanisms involved in therapeutic resistance and tumour recurrence have not yet been fully understood and mostly remain unexplained. Without doubt, an improved understanding of the cellular machinery contributing to recurrence will pave the way for the development of novel, sophisticated and effective antitumour therapeutic strategies which can eradicate tumour without the threat of relapse.