In solid tumours, the presence of regions of abnormally low oxygen levels (i.e., hypoxia) is recognised as a major driver of tumour progression and therapeutic resistance. Yet, how exactly oxygen levels shape cancer cell responses and disease dynamics in vivo remains poorly understood. While in vitro models of hypoxia exist, they often fail to capture the complex oxygenation dynamics of real...
Tumor growth and angiogenesis drive complex spatiotemporal variation in micro-environmental oxygen levels. Previous experimental studies have observed that cancer cells exposed to chronic hypoxia retained a phenotype characterized by enhanced migration and reduced proliferation, even after being shifted to normoxic conditions, a phenomenon which we refer to as hypoxic memory. However, because...
Cancer populations evolve in response to dynamic microenvironments, and the adaptive immune system responds by attempting to recognize and eliminate cancer cells by targeting tumor-associated antigens. The interplay between an evading cancer and recognizing immune compartment is quite dynamic and results in cancer elimination or ultimate immune escape preceded by a period of sustained...
Tumours are subject to external environmental variability. However, in vitro tumour spheroid experiments, used to understand cancer progression and develop cancer therapies, have been routinely performed for the past fifty years in constant external environments. Furthermore, spheroids are typically grown in ambient atmospheric oxygen (normoxia), whereas most in vivo tumours exist in hypoxic...
Tumor microenvironmental factors change over time, and these factors include hypoxia and the extracellular matrix (ECM). Experimental studies demonstrated that oxygen levels fluctuate between normoxic and hypoxic levels, a phenomenon known as cyclic hypoxia. This fluctuation facilitates intratumoral cellular heterogeneity. However, how cyclic hypoxia shapes the landscape of tumor invasion is...