Scraped knees, leukemia, sore throats, and lymphomas have more in common than you would think. All of them are biological wounds that manipulate the body’s intrinsic wound healing pathways. There are many parallels between tumours and aberrant wound healing processes, to such an extent that a new hypothesis for cancer proliferation has been postulated (Meng et al., 2012). The proposed immunosurveillance theory highlights the similarities between cancer progression and innate wound healing (Meng et al., 2012). This hypothesis suggests that tumours are akin to biological parasites, in that they can manipulate host immune systems to manufacture an ideal external environment for their survival and subsequent proliferation (Dvorak, 2015).
The current connotation of cancer is referred to as the “mutational theory” of cancer proliferation (Meng et al., 2012). While it is often sufficient in describing the prevailing manner in which tumours arise, there are several significant outliers that cannot be attributed to solely spontaneous mutations (Meng et al., 2012). One such outlier being the probability of developing cancer in the average human lifetime (Meng et al., 2012). Theoretically, if one mutation is all that is required to develop cancer, the probability of any individual developing cancer is much higher than the actual disease incidence (Meng et al., 2012). With 10^12 stem cell divisions per day in the average adult human and a point mutation rate of 1.1×10^-8, everyone would have the chance of forming 10,000 cancer cells, per day (Meng et al., 2012).
In addition to the discrepancies discussed, the mutational theory cannot account for the differences in time required before cancer incidence in different species. For instance, humans and rats have the same DNA replication time but greater than 50% of all Sprague-Dawley rats will develop cancer by age two, while human children less than two have chances less than one in a million of developing cancer in the same timeframe (Meng et al., 2012).
Following any injury to the body, platelets and their associated proteins regulate angiogenesis (the formation of new blood vessels during vascularization), a process that is essential to stimulate and engage the biological repair process (Meng et al., 2012). Similar processes have been exhibited with cancer, forming the basis of the immunosurveillance theory. It has been found that tumours, both benign and malignant, utilize platelets when constructing their micro-environments and vascular domains (Dvorak, 2015; Pietramaggiori et al., 2008). To survive, tumours need an influx of resources and nutrients and a means of eliminating their metabolic waste products (Dvorak, 2015; Pietramaggiori et al., 2008).
While liquid tumours like leukemias already have access to abundant nutrients and waste disposal pathways in the circulatory system, solid tumours require more complex techniques to survive and proliferate (Dvorak, 2019). Through the extortion of host platelets, solid cancerous masses are able to design their own vasculature, maximized for nutrient delivery and elimination (Dvorak, 2019). This interconnectedness between cancer and wound healing is seen above in Figure 1. Cancer incidence increases proportionally with wound incidence and does not start to slow until wound healing abilities are significantly reduced at advanced ages, indicating the reliance of cancer on host immune response pathways (Figure 1) (Dvorak, 2019).
The immunosurveillance theory views cancer as an emergent property of a hijacked immune response pathway and can address some of the statistical disparities encountered with the mutational model. This divergence from the mutational theory provides an alternate perspective into the disease mechanism as a whole, which may in turn catalyze future innovations in oncology.
References
Dvorak, H.F., 2015. Tumors: Wounds that do not heal–Redux. Cancer immunology research, 3(1), pp.1–11.
Dvorak, H.F., 2019. Tumors: Wounds That Do Not Heal—A Historical Perspective with a Focus on the Fundamental Roles of Increased Vascular Permeability and Clotting. Seminars in Thrombosis and Hemostasis, 45(06), pp.576–592.
Meng, X., Zhong, J., Liu, S., Murray, M. and Gonzalez-Angulo, A.M., 2012. A new hypothesis for the cancer mechanism. Cancer Metastasis Reviews, 31(1–2), pp.247–268.
Pietramaggiori, G., Scherer, S.S., Cervi, D., Klement, G. and Orgill, D.P., 2008. Tumors Stimulate Platelet Delivery of Angiogenic Factors in Vivo. The American Journal of Pathology, 173(6), pp.1609–1616.
Comments
5 Responses to “Cancer; Always healing, never healed”
Hey everyone!
I recently encountered an article that analyzed the widely-accepted mutational model of cancer and thought it would make for an interesting blog topic. I personally really enjoyed writing the probability section, seeing as mutations occur so frequently in our body and yet cancer incidence is not observed proportionally.
I’d appreciate any feedback you have on this post, thank you ahead of time!
Cheers,
Paige
Hi Paige,
Great blog post! It was really interesting and engaging, and well-written. I didn’t know about immunosurveillance theory before, so I definitely learned something new!
I have some suggestions:
– (P1,S3) The word “cancer mechanism” here is a bit ambiguous. Do you mean a new hypothesis for cancer proliferation?
– (P1, S4) Is the “new hypothesis for cancer mechanism” the immunosurveillance theory? if so, it would be best to directly state that, so that readers are able to make that connection.
– (P1, last sentence) I would rephrase this to say ” This hypothesis suggests that tumours are akin to biological parasites, in that they can manipulate host immune systems to manufacture an ideal external environment for their survival and subsequent proliferation.”
– (P2, S2) What is the “prevailing behaviour” of tumours. I suggest being specific. In addition, I would suggest splitting this sentence into two, with the second sentence stating “One such outlier is the probability of developing cancer in the average human lifetime.”
– (P2) You first introduce “Mutational Theory” with capitals on both words. However, later in the sentence, you write “mutational theory.” In order to be consistent, consider changing one of these. I would also begin a new paragraph with the words “In addition” as you are introducing a new idea that could be its own separate paragraph. This is up to you though!
– (Figure 1) I suggest placing this figure after it is mentioned in text, not before.
– (P3, S1) I suggest placing ” the formation of new blood vessels during vascularization” in brackets.
– (P3, last sentence) You mention that the decrease in cancer incidence decreases as the body’s capacity for wound healing decreases, however, it is not immediately clear how wound healing is related to the immune system. Consider specifying this to make the point clear.
– Your whole blog post is about the immunosurveillance theory, but there is no mention of this past the first paragraph. I suggest brining this up in later paragraphs as well, so that readers can make connections to the ideas you introduce in the first paragraph. At the very least, you should mention “immunosurveillance theory” in your conclusion paragraph.
– It would be good to directly state some future directions of this research in your conclusion, as it should be longer than one sentence.
– Some of your paragraphs are a bit long. It might be good to separate them into small paragraphs. However, this is definitely more of an individual choice, not something that you absolutely have to change!
Overall, great blog post! I liked learning about how cancer cells can be thought of as biological parasites as per the immunosurveillance theory. I hope you find my suggestions helpful. Thanks for an amazing read!
Happy editing,
Keshikaa
Hey Keshikaa!
Thank you so much for your helpful suggestions, I made sure to incorporate them into my final edits. I’m glad you enjoyed the read, I definitely found the premise fascinating, seeing as I had previously thought there was no disagreement on the origin of and mechanism of cancer proliferation.
Thanks again, much appreciated!
Paige
Hello Paige,
This was very interesting to read! I extremely appreciated the smooth transitions between each sentence and paragraph. Here are some suggestions:
1. As suggested by Keshikaa, I think splitting up the long paragraphs would be helpful.
2. In the figure caption, you may want to briefly state the specific trends towards which you want to draw the reader’s attention.
3. Although you have a good number of citations, I would suggest adding a greater variety of them in each paragraph. This way, the blog will seem to be an amalgamation of information from different sources as opposed to being a sequential compilation.
Overall, I enjoyed this very much! I hope the comments help.
Happy editing!
Lisa
Hey Lisa,
Thank you for taking the time to read this post and give feedback, I definitely took your comments into consideration when finalizing this post. Splitting up the paragraphs definitely help with the aesthetics of the post and discussing the trends in the figure caption were both helpful suggestions!
Cheers,
Paige