Understanding the Genius that is Cancer

As a cancer tumor grows, it needs to receive adequate nutrients (which are carried through the blood) and thus angiogenesis, or the growth of new blood vessels, is a vital element of the tumor's survival. This principle became the focus of many antiangiogenic drugs, which aim to inhibit vascular endothelial growth factor (VEGF), a promoter of angiogenesis. This strategy would stunt primary tumor growth and effectively prolong the patient's life. The review "Silencing of Fueling Metastasis with VEGF Inhibitors: Antiangiogenesis Revisted" by Loges et. al (full text can be accessed here), explains that contrary to popular belief, inhibition of angiogenesis often promotes tumor invasiveness and metastasis.


As part of the cancer defense against antiangiogenic drugs, the cells undergo a natural selection of the cells that can survive hypoxic conditions (these cells rely on glycolysis for energy and thus are glucose addicted). Metastasis is induced, in part, because the tumor vessels themselves become leaky and cells then traverse the circulatory system, but also because the cells themselves look for new, oxygenated tissue to call home.



I found this review rather thought provoking; it leads us further into the core of cancer growth. It is often said that you learn a lot more from a mistake than you do from anything else. By no means are VEGF-inhibiting drugs "mistakes", but understanding how cancer cells evade and metastasize in response to the drug will enable scientists to perhaps pinpoint factors that contribute to metastasis.

Here are some things that really got me curious:

1) As the cancer cells that cannot survive hypoxia experience apoptosis, is it possible to mimic this signal to, in a sense, outsmart all cancer cells?

2) Does the cancer's ability to survive without angiogenesis minimize the importance of angiogenesis? In other words, can scientists create a hierarchy of hallmarks and therefore develop more effective treatments by following a systematic approach based on the most critical to least important pathways?

3) Is concomitant drug treatment beneficial or does it promote the cancer to develop better mechanisms of evasion?

4) The genius of cancer is really intriguing and poses the dilemma of treating the cancer directly versus giving the cancer more treatments to select against, thus evolving into an indestructible tumor.

5) With the knowledge that antiangiogenic drugs causes metastasis at a faster rate, is there a way to use this to our advantage and in a sense "direct" the metastasizing cells to certain locations?

There are many different ideas that can stem from this review, and these were just a few. Feel free to bring up any other important questions/concerns!