Hypoxia has been a hot topic of research in recent years. Its strong association with tumour propagation, progression, and particularly resistance to therapy has made it one of the most interesting issues in oncology. Read our blog below to find out more about hypoxia, its role in cancer development, and a promising drug target for anti- cancer agents.
What is Hypoxia?
Hypoxia refers to diminished availability of oxygen to the body tissues. It can be ‘generalised’, affecting the whole body or ‘localised’ to a specific tissue or region of the body. Although not as threatening as anoxia (absence of oxygen), hypoxia can also lead to serious complications if not checked in time. Some common symptoms include disorientation, hallucinations and cyanosis or bluish discolouration of skin.
Hypoxia evokes a complex molecular response on a cellular level, forcing poorly oxygenated cells to adapt. However, in some cases, this seemingly obvious behaviour can have very dramatic consequences. Below we have discussed one such problem and the impact it has on cancer patients.
Hypoxia in tumour cells:
Tumour tissues quickly outgrow their blood supply and are therefore less oxygenated than the rest of the body. Such low oxygen concentrations not only enhance malignant progression, but also increase resistance to radiotherapy, a major concern for oncologists. Tumour tissues recruit monocytes where they differentiate to form tumour-associated macrophages (TAM) under hypoxic conditions. These differentiated macrophages or TAMs exhibit pro-tumoural activity and actively promote all aspects of tumour initiation, growth, and development. Growth factors released by TAMs attract more TAMs and other tumour promoting immune cells to the tumour, amplifying a feed- forward loop.
Depending upon the microenvironment, monocytes can be polarised to either M1 or M2 macrophages. Hypoxic tumour cells produce cytokines that direct macrophage polarisation to the M2 phenotype (displayed by TAMs). The M2 phenotype is known to be associated with pro-tumoural function, as opposed to M1 macrophages that show anti-tumoural features. Reprogramming TAMs to M1-like macrophages would thus be an efficient way to prevent tumour progression. As TAMs are so crucial to disease evolution, they are being increasingly recognised as promising drug targets for anti- cancer agents. Fit- for purpose bioassays are required to screen therapeutic compounds that can act on these cells and stop the disease from progressing.
Our experienced team of scientists have developed a physiologically relevant human cell-based assay to screen a panel of small molecules for anti-tumour effects. Follow the link to our poster and find out more about this assay.
Are you looking for a suitable bioassay to develop novel anti-cancer drugs? Get in touch with our team to discuss your project and take your compound to the next stage.