Cancer

tumblr_m8i0x4P2ob1qg1up7o1_500This blog post considers the modules relating to cancer from the recommended text book General Pathology by J.J. Rippey and how engagement with this material has changed my previous understanding of the disease. I explore how cancer is such a simple concept on a molecular basis and yet there is a high complexity to individual cancers making many of them very difficult to treat. I also briefly look into some of the molecular similarities between the pathogenesis of auto-immunity and cancer.

Before engaging with these modules my preconceived understanding of cancer was limited in that I didn’t really know much about the pathophysiology of cancer. I knew that cancerous tumours were due to abnormal cell growth and that these cells had the ability to spread in the body. I had a feeling for how complicated and difficult it was to treat cancer but had no clear understanding as to why.

I believe that in some way I thought that cancer was somehow something alien to the body even though I rationally knew that it came from within. But now, I see how intimately it is bound to the body, how it is a completely natural progression within the body when there is a loss of growth regulation, how the tumour cells are striving to survive with the same tenacity as physiologically normal cells. While reading in preparation for this blog there were certain things that jumped out for me in particular as they are new to me. One of these is that neoplasms seem to behave as parasites! “Tumour cells do not grow in isolation, but require a supporting connective tissue framework, which is not in itself tumourous” (Rippey, 1994: 244). They secrete growth factors that promote angiogenesis, attract and stimulate formation and penetration of vessels, lymphatics and nerves – creating this framework, that comes from the host, to support their nutritional and metabolic needs. (Rippey, 1994)(Leisegang, 2012) In doing so, they compete with normal cells and tissues. (Leisegang, 2012) This shows that all tumours have two basic components – the parenchyma cells of the neoplasm which dictates biological behaviour of the tumour, and the supporting framework that is derived from the host and is not neoplastic (this is crucial to the growth of tumours). (Leisegang, 2012) Another aspect of cancer pathophysiology that was new to me is that not all cancer cells are able to metastasise, that there are several stages necessary for metastasis to occur and for a tumour cell to be able to do this it must have certain attributes. (Rippey, 1994) This process is shown in the video below. (MechanismsMedicine, 2012)

 

molecular basisOn a molecular basis, cancer is such a simple concept. The diagram to the left, from our carcinogenesis module notes, is a simplified scheme of the molecular basis of cancer formation and clearly demonstrates this concept. (Leisegang, 2012: 6) Yet individual cancers are highly complex and many are difficult to treat. Why is this the case? The slides below show how cancer starts with multiple mutations involving many genes in cellular DNA; and how the mutations occur not only in the oncogenes, tumour suppressor genes and DNA repair genes but also in quite a few others, as can be seen below. (National Cancer Institute, 2013) Due to the build-up of mutations in these genes being a random and haphazard process, an individual evolution in response to the body’s selective pressures, cancers are actually extremely diverse diseases as every patient’s cancer is unique! (Evans, 2012) Also, ‘cancer cells adapt and evolve in response to treatment’, rendering drugs less effective over time in two ways – compensation and evolution. (Evans, 2012) They can compensate by working around the biological systems that are blocked by cancer treatment, and they can evolve if mutant daughter cancer cells resistant to the cancer treatment spontaneously come about. (Evans, 2012)

cancer49

cancer50

In reading the modules on auto-immunity I noticed that there were some molecular similarities between the pathogenesis of cancer and auto-immunity in that they both share very similar environmental factors as aetiologies for their initiation as well as a genetic predisposition not being enough of a trigger, they both need the environmental factors to trigger an autoimmune response or tumour development. The environmental factors I refer to above are hormones (oestrogen sensitivity), drugs (comparable mechanisms to molecular mimicry), UV radiation (can damage DNA and modify self-antigens) and infection (not as clearly implicated in auto-immunity as cancer but may be able to form immunogenic units that bypass T-cell tolerance). (Leisegang, 2012) There is even a very interesting review linking lymphocytes and cancer cells called The cancer stem cell: Evidence for its origin as an injured autoreactive T Cell – it is definitely worth a read! (It can be found here)

Cancer-CellIn conclusion, the study of these modules on cancer and auto-immunity has deepened my understanding of cancer and cleared up some murky areas in my perception of the pathophysiology of cancer. I now see why, due to their bewildering genetic variety, individual cancers are so difficult to treat; and that there are some interesting similarities between the pathogenesis of cancer and auto-immunity.

 
References

Evan, G., 2012. Expert Opinion: why are some cancers so difficult to treat? Cancer Research UK Science Update Blog, [blog] 26 January. Available at: <http://scienceblog.cancerresearchuk.org/2012/01/26/expert-opinion-why-are-some-cancers-so-difficult-to-treat/&gt; [Accessed 19 April 2013].

Leisegang, K., 2012. Tumours and their Classification, NAT311 General Pathology. University of the Western Cape, unpublished.

MechanismsMedicine, 2012. Introduction to Cancer Biology (Part 3): Tissue Invasion and Metastasis. Available at: <http://www.youtube.com/watch?v=bdWRZd19swg&gt; [Accessed 19 April 2013].

National Cancer Institute, 2013. Understanding Cancer Series. [online] Available at: <http://www.cancer.gov/cancertopics/understandingcancer/cancer/AllPages&gt; [Accessed 19 April 2013].

Rippey, J.J., 1994. General Pathology. Johannesburg: Witwatersrand University Press.

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s