on inducing apoptosis in cancer

the lecture i attended was quite complicated, therefore much to my liking, and extremely catalytic in terms of my commitment to continuing, self-directed, multidisciplinary studies.

here's the gist of Suzanne Cory's report: apoptosis is a constantly occurring, vital process in normal physiology, the mechanism of homeostasis. we're constantly producing new cells, for example, particularly in the liver, gut and immune system, and without this very complex process of apoptosis to regulate tissue formation and system ativities, we would, as professor Cory put it, explode.

when cell birth is equal to cell death, we have dynamic balance, which is what homeostasis means. but when cell death rates are higher than those of cell generation, we have the foundation for all the degenerative, wasting diseases; when cell birth prevails over cell death, a disposition to oncogenesis is created. it's this impairment of natural cell death that researchers term the "central step in tumour development."

apoptosis itself is an interesting mechanism. under its chain of influence, cells shrink, chromatin compacts, DNA is cleaved, cells 'bleb', and are engulfed by macrophages. the process has no lysis component and therefore produces no inflammatory response. apoptosis is a genetically programmed event that every human cell is capable of. it plays a key role, for example, in sculpting embryonic tissues, as when it deconstructs the webbing between our fingers and toes during later stage in-utero development.

apoptosis-inducing proteins have a hydrophilic tail that binds to mitochondrial membranes, creating leaks which spill contents into the cytoplasm and impair healthy regulation and cell translation, which in turn activates another family of proteins called caspases that trigger the cells to take an active hand in their own death.

current research (from late nineties onwards) is focusing on undoing the dominant pro-survival, oncogenetic proteins, creating various molecules to mimic the guardian, pro-death proteins that can bind to cell walls in their place, activating caspases which in turn trigger cell suicide. its not as simple as it sounds, since not every cancer has the same oncogenetic protein trigger, so at the moment they've only had success with a mimetic called ABT-737 which binds to only 3 of the pro-survival proteins, a class called BH3s. these appear most effective, for example, with follicular lymphomas [for example, the class of molecules called Bcl-XL has been fingered in lymphoid and epithelial cancers; A1 in stomach cancers; Mcl-l in multiple myelomas, etc].

sideeffects seem vastly more manageable than chemo or radiation: this kind of 'translational medicine', as she called it, which presumes to correct flaws in the copying of DNA information as cells replicate, can trigger unwanted platelet and lymphocyte death which she termed 'manageable...' [this is still an approach to medicine that tinkers with symptomatic consequence rather than eliminating root causes {ie. investigating why the DNA creates the copying errors in the first place as a holistic system wide event, not just a glitch at one level of cellular organization}, but as mechanical medicine gets more sophisticated one hopes patients have a better chance of surviving treatment and this is good news for fans of conventional treatment]