Abstract
Cancer is a heterogeneous group of disorders linked by unregulated growth of abnormal cells characterized by several genetic aberrations. Hypoxia is a phenomenologic concept produced by lack of oxygen. It depends on the demand of the cells and tissues of the organ. Approximately 90% of cancers are solid tumors; the rest are hematologic cancers. Hypoxia seems to play a major role in most solid tumors in their characteristic behaviors.
A cancer cell is the most evolved, rapidly adapting moiety, probably in the universe. The evolutionary abilities of the cancer cell program it to continue to grow and multiply even under adverse conditions. Hypoxia occurs in a tumor even when it is as small as 5 mm. The genetic alterations in the hypoxic cell are several. Equally important are the production and release of cytokines such as vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF-1), and mutation in the p53 gene. The HIF-1 is known to bind to hypoxia response elements, which aid in angiogenesis and metastasis.
We know that the tumor stage grade can predict hypoxia. Why is hypoxia important for the oncology community? It is important because it has several implications for imaging and therapy, including radiotherapy and chemotherapy. There have been elegant intratumoral oxygen measurements to correlate this concept of hypoxia and its clinical relevance. One of the newer imaging modalities is the positron emission tomography scan that uses the principle of increased fluorodeoxyglucose by metabolic cancer cells. In hypoxia, this modality can be misleading and warrants use of other 18F- fluoromisnidazole (FIMSA), FAZA, FETA, EF5, and Cu-ATSM that can accurately image even hypoxic tumors. The studies with FIMSA have shown that it can predict survival based on the delineation of the tumor vasculature and hypoxia. Hypoxic cells are resistant to radiotherapy, and several other techniques and the addition of hypoxic sensitizers need to be used concomitantly.
Understanding the molecular biology of the hypoxia-induced substances, we now have engineered molecules such as bevacizumab—a monoclonal antibody to target VEGF. We also have several other monoclonal antibodies and tyrosine kinase inhibitors that target this VEGF pathway and others activated by hypoxia. Thus, an understanding of hypoxia and its consequences is vital to tackle the epidemic of cancer. Although cancer is a genetic disorder involving interplay between dominant oncogenes, tumor suppressor genes, and housekeeping genes, we also understand the profound role hypoxia plays in the subsequent progression and metastasis.
How is this relevant to our community of high altitude hypoxia? We could use the knowledge gained from the oncology community to apply the same principles to fathom high altitude hypoxia. Cross-community collaboration can bring about more meaningful information. As I mentioned earlier, the cancer cell is the most evolved moiety in this universe; we could learn from it its survival tactics and apply them to the larger moiety—human beings—in their quest for adaptation and survival in extremes of conditions.