Interesting Effects of Hypoxia in Cancer

The Effects of Hypoxia in Cancer

The hypoxia is due to the following mechanism: a decrease in breathable oxygen, reduced or cardiopulmonary failure. The lungs are unable to transfer oxygen from the alveoli to the blood efficiently. If blood oxygen levels are too low, your body may not work correctly. Diseases of the blood, heart, circulation, and lungs may be the most common causes of hypoxia.

A variety of conditions can interfere with the body's ability to send normal oxygen levels to the blood. Still, the hypoxia side effects can be fatal if severe in the short term and can affect the heart or brain if it persists over a long period. Hypoxia or deficient oxygen supply to tissues characterize a series of pathological situations, including cancer.

The hypoxia in cancer is a common feature in solid tumors, contributing locally and systemically to tumor progression. Hypoxia alters cancer cell metabolism and contributes to therapy resistance. As evident in advanced metastatic cancer, a hypoxic environment is often established, which plays an essential role in cancer evolution.

Cancer is a significant public health problem worldwide with few effective treatment choices, poor prognosis, and high mortality rates. The rapid growth of a tumor leads to depletion of its oxygen supply. This results in a reduction in oxygen supply to some regions of the tumor, which is significantly lower than the supply level to healthy tissue.

Hypoxia is due to any condition that reduces or impedes blood circulation in any area of the body. Hypoxia alters cancer cell metabolism and contributes to therapy resistance. Hypoxia side effects generate intratumoral oxygen gradients, contributing to the plasticity and heterogeneity of tumors and promoting a more aggressive and metastatic phenotype.

The rapid growth of tumors means that their increase in size is not accompanied by adequate vascular development, which generates hypoxia within the tumor mass. Due to the insufficient blood supply, these areas are impervious to chemotherapy and ionizing radiation. There are a series of factors that increase or decrease cellular radiosensitivity, O2 being very important since oxygen is the universal radiosensitizer and enhances the action of radiation in all types of cells, which has a very great therapeutic value.

Cancer cells have developed adaptive mechanisms that allow them to survive in these unfavorable conditions. Initial or moderate increase of hypoxia-inducible factor (HIF) α levels could lead to cell adaptation, and in the absence of oxygen, cancer cells adjust to their new microenvironment mainly by angiogenesis stimulation by vascular endothelial growth factor.

Currently, to combat hypoxia, clinical trials are being conducted in which the increase of hemoglobin is promoted, and techniques are used to increase its concentration. Treating both hypoxia and anemia in cancer patients has been shown to result in greater local-regional tumor control, more prolonged survival, and improved quality of life.

In cancer treatments, it is essential to avoid tumor hypoxia since oxygen is a powerful radio-sensitizer, so preventing or neutralizing it will ensure more significant destruction of the tumor mass. The use of cell-based targeted nanoparticles for effective therapy has been highlighted as a dual-mode treatment strategy to combat drug resistance and improve the efficacy of chemotherapy. Some anticancer drugs targeting HIF have proven successful in slowing or halting tumor growth. Hypoxic prodrugs are activated by cellular reductases, reoxidized into initial drug progenitors in anoxic cells, and converted into cytotoxic substances.

Several proteins have been determined to be over-expressed during hypoxia in cancer cells. Many studies have concluded that HIF-1α, BNIP3, PDK1, and GLUT1 proteins can be used as markers to uncover hypoxia. HIF-1a has been found to stabilize under hypoxia. It then moves to the cell nucleus and increases the transcription rate of genes that control oxygen release, helping the cancerous cells become accustomed to the lack of oxygen. These proteins are considered potential biomarkers of hypoxia and can be recognized with various imaging techniques.

Research is ongoing to discover how this information can be used to develop new forms of therapy and measurement of hypoxia in cancer. There is a promising complementary treatment in the form of a cream that has been shown to target and kill diseased cells. Read some inspiring stories from people that already used this new treatment. Visit the testimonials page.

Sources

• Francisco Arvelo y Carlos Cotte. (2008) hipoxia en la malignidad del cáncer, Laboratorio de Cultivo de Tejidos y Biología de Tumores. http://ve.scielo.org/pdf/ic/v50n4/art12.pdf

• Fredrik Bajer (2009) Targeting newly discovered oxygen-sensing cascades for novel cancer treatments Biology, equipment, drug candidates. cordis. https://cordis.europa.eu/project/id/502932/es
• Jing, X., Yang, F., Shao, C. (2019) Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Molecular cancer https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-1089-9#article-info

• An. R. Acad. Nac. Farm (2010) Hipoxia y cáncer, analesranf. https://analesranf.com/wp-content/uploads/2010/76_03/7603_01.pdf

• Sara Strese, Mårten Fryknäs, Rolf Larsson and Joachim Gullbo (2013) Effects of hypoxia on human cancer cell line chemosensitivity, BMC Cancer. https://www.researchgate.net/publication/247154112_Effects_of_hypoxia_on_cancer_cell_line_chemosensitivity