Cancer has always fascinated me on both a scientific and non-scientific level. As a deranged cellular process, the disease reveals an intricate system of checks and balances and underscores how little we actually know about the maddeningly complex “cross-talk” that Bruce Alberts compared to cell “thinking.”
Until last year, I considered cancer to be an isolated biological process. It was easy to see how the cell cycle can be sabotaged, how certain checkpoints can be bypassed and normal cellular proliferation permitted to run amok. In my head, there was a solid cadre of proteins automatically associated with cancer…p53, Bcl-2, Rb.
However, a syllabus chapter on neoplasms last year changed my view of cancer cells by pulling together information in a suggestive fashion. In normal tissue like the gut or skin, we have stem cells that continually divide into daughter stem cells and cells destined to terminally differentiate and die. Only these stem cells enjoy limitless replicative potential, and differentiation means that the cell has a one-way ticket to dying without any heirs. The syllabus also talked about how cancers can be pathologically graded based on differentiation, and that less differentiated cancers are fiercer adversaries – as though the degree to which a cell has regressed back from its terminally differentiated state reflects how feral and uncontrollable the cell has become.
And then I wondered if cancer cells had achieved the impossible…did they manage to somehow reverse the laws of nature and learn how to de-differentiate in a misguided bid for “stem cell-hood” and immortality?
In another tangent, I had never been interested in the links between inflammation and cancer until an analysis from a pilot project at Stanford showed that the only proteins associated with survival were two cytokines, IL-1 and IL-7. Suddenly, I was interested in how inflammation can affect cancer survival. The connection had never been vitally interesting before, even though it was also mentioned in the syllabus in passing. Another event that sparked my interest in the connection between immunity and cancer was writing about an ongoing UCSF brain tumor vaccine trial for Synapse, which described harvesting the tumor cells and cultivating protein complexes to boost immune response to the tumor. Although it still seems unclear to me how the whole immune system vs. cancer situation exactly works, I really like the connections.
No one else will agree with me, but the most outstanding lectures in Cancer block so far were given by Dr. Doug Hanahan on the topics of angiogenesis and metastasis. For some reason, his lectures really seemed to address where my thoughts on cancer biology have been turning to. There was an interesting mention of an “angiogenic switch” and the idea that there are “bad” inflammatory cells, fibroblasts, etc. that somehow aid cancer cells. In the metastasis lecture, I was intrigued by the notion that metastasis resembles a “re-awakening” of the far-flung migratory habits of cells during embryonic development. Re-reading Hanahan’s syllabus chapters made me intellectually excited. In the end, these two processes – angiogenesis and metastasis – are two of the keys to fully understanding cancer and how to cure it.