Abstract
Metastatic cancer is the final frontier in disease progression with few avenues of treatment open to patients. The failure of therapeutic options at the end-stage disease is confounded by the presence of diverse clones in the metastatic tumor which contributes to intratumoral heterogeneity (ITH), resulting in intrinsic and acquired drug resistance. We aim to elucidate the contribution of ITH to the development of metastasis with a focus on the origins and molecular mechanisms driving ITH, as well as the clinical and technical challenges of acquiring and studying metastatic cohorts in which we can investigate this phenomenon. Bioinformatic approaches that could help in silico analysis will be discussed, which could shed light on how to design new therapeutic strategies for metastatic cancer and give hope to patients living under the shadow of the sword of Damocles.