TEDxConejo - Dr. Glenn Begley - The Complex Biology of Cancer (or Why Haven't We Cured It Yet?)

[@brcarter1111]

The first part about understanding cancer is knowing you can never understand cancer. With nearly every "rule" in oncology, there are notable exceptions. This is due largely to the heterogeneity, or differing composition, of tumors and cancer. Many oncologists don't even agree on what causes cancer; some saying it's the Warburg effect, others say its viral infections, hypoxia, epigenetic alterations, mutations, vitamin and nutrient deficiencies, chromothripsis, etc etc, the list goes on. All these scientists will provide measurable data to support their conclusions, but at the end of the day we can only observe cancer in retrospect. When he states that tumors take many many years to form, most oncologists agree they take between 10-30 years to form. What about paediatric cancers? Scientists who study cancer need organisms with cancer to study. They frequently administer a chemical called 3-methylcholantrene, a powerful carcinogen, that can cause cancerous tumors to form in weeks. Cancer is the single greatest problem nature has ever thrown at us. It is the dark side of evolution that ushers in endless forms most hideous. We understand the inner workings of stars, we put a man on the moon, we communicate at the speed of light and understand the origin of our universe, yet we don't understand how cancer is spreading....

[@KumariKumari-fw7nc]

I think cancer is mostly genetic..

[@brcarter1111]

@@KumariKumari-fw7nc Difficult to say really. I would say with a high degree of certainty the formation of a tumor is genetic, but the progression to cancer is almost certainly not, as metastasis seems to be an event that relies on genetic conservation. The EMT program seems to be directed by epigenetic change.

[@brcarter1111]

@@KumariKumari-fw7nc I disagree adamantly. When we look at the process by which cancer forms, it often begins with the formation of a tumor. The problem is most members of the public, and also scientists, conflate "tumor" with "cancer", but the processes that govern these events are different. Clearly, mutations play a critical role in tumor formation. it is the loss of function in tumor suppressor genes that prevent intrinsic immune mechanisms from preventing the tumor from growing or killing them, and it is often gain of function mutations that create oncogenes that facilitate growth. The interesting thing though, is that new research is indicating pretty convincingly that the process of metastasis is not driven by mutation. Metastasis is the process by which cancer cells separate from the primary tumor, enter the circulatory and lymphatic system, exit, and generate new secondary tumors. This process separates a benign tumor from a cancerous one. What we are learning is that in contrast to tumor formation, this process is heavily genetically conserved and requires numerous genes to become activated in concert in a concise, step-wise progression where each step must correctly preceed the next, or the entire process fails. A major clue came from the discovery that cancer cells revert back to a stem-cell like state (driven by the activation of intact genes), as well as a complex cellular process called the epithelial mesenchymal transition. This is a complex cell program that allows cells to gain the ability to move, follow signalling molecules, then return to an achored state. Interestingly, one of the only times we see these genetic programs activate together is in embryogenesis and very early pregnancy. The activation of the stem cell and EMT programs are almost certainly driven by epigenetic events, not mutations.

[@ludicrousitymegan]

Such a brilliant talk. Totally changed my understanding of cancer. Thanks Glenn.

[@johnstewartvet]

Well explained. Those not previously exposed to the cellular basis of cancer may need to watch it 3 to 5 times before they get all the value out of it

[@RhondaLeeQ]

Thank you for helping me understand! xo

[@medichain]

It has been only 7 years ago since this TedMed lecture was held. The most effectieve therapy in 2011 was the combination of several unspecific anti-cancer chemotherapeutics, called adjuvent therapy. It is amazing how the progres in the knowledge of moleculair genetics has changed the Arsenal of personal therapeutic options in 2018.

[@kreteman777]

Yeah but outcomes aren't much better.

[@KumariKumari-fw7nc]

I think immunotherapy is the answer. Make a cancer patients immunity very strong, so that it is able to attack cancer cells successfully..( I am not a scientist -say

[@oibal60]

This explains everything. I am forwarding this to friends and social media.

[@lengtayguan1109]

Great talk

[@bigmacbricky4866]

There’s a prevention out there somewhere we just need to find it. Thinking caps on everyone!!

[@mrstevebournias]

Excellent!!

[@lucaspierce3328]

Evolutionary oncology and related fields, along with evo-devo, ecology and many other studies are what I'm studying.

[@robynelms4323]

Hello there. Thank you so much for this. It was very insightful. You say that the common misconception is that cancer develops quickly, but this is as we are taught to believe this in college. I believe you, but how come schools teach us cancer can be targeted because it develops quickly (like hair cells) if it is wrong? I just would like some clarification. Also, I believe you in that we will be able to address cancer, and I am intent on doing this in my career. This presentation has been a wake up call that I need to learn more about cancer and if I am finding out simple things I didn't already know, my knowledge in cancer isn't sufficient. Thanks again. :) (I'm from the UK BTW-maybe our curriculum content is different on cancer?)

[@davidaustin6962]

+RobYn with a Y I believe the masses grown quickly compared to the cells around it, precisely because the cells are immortal, but not because they reproduce quickly.

[@brcarter1111]

I've been researching cancer for about 9 years now so I might be able to help you understand it. The crux of cancer is what is written between the lines; what cancer truly is. We often see mutations in genes involved in DNA repair, the cell cycle (cell division), and responsiveness to immune signals that kill damaged cells. When you put these three things together, you get evolution incarnate. Because the ability to repair DNA is compromised, this leads to the slow accumulation of more mutations and changes over time. When a single cell acquires a mutation, only this cell and the cells that it divides into will have it. Many of the cells die, but others are able to maintain enough stability to survive, and the ever tinkering hand of natural selection decides which cancer cells survive and reproduce. This leads to a population of cells that are incredibly diverse and have different properties. We hear about many compounds that "kill cancer cells", but more realistically, these treatments kill SOME cancer cells. What remains will survive and replace the cells that have been killed, and the previous treatments will no longer be effective. This is like spraying for mosquitos; each time we do it the pesticide will kill a massive portion of the population, but some of the mosquitos have previously acquired random mutations that make them immune to the pesticide. If you apply the same pesticide the following year, it won't kill any of the mosquitos. This also leads scientists to have an extremely hard time characterizing cancer, because so much of it is driven randomly. Eventually, cancer cells are able to express genes they shouldn't, and some even revert back into stem cells. I was a forensic scientist and decided to push the reset button on my life and career to return to school to study this disease. I started out asking many of the same questions you are asking now, so I feel for ya. LMK if you have any questions and sorry for the novel ;) (and p.s., our hair is made of proteins, not cells)

[@IndigoMist44]

@@brcarter1111 Oh wow! That gave me the impression that pesticides and cancer treatments do seem to have quite a bit in common in regards to natural selection aiding those they target.

[@brcarter1111]

I think I can answer your question. I believe you are mixing up cancer development (oncogenesis) with cancer cell division. For most cancers, the process of oncogenesis typically takes between 10-30 years and is a slow process. Obviously, in the sad case of childhood cancers, this is not always the case, and some cancers can form in a period of weeks if induced by a carcinogen or virus. Cancer cells in reality actually divide much, much slower than healthy cells, as they often have over triple the amount of chromosomes. The reason they "divide faster" as people say is because normal cells have long periods of function after mitosis (G0 and growth phases), whereas cancer cells are repeatedly pushed back into the cell cycle by oncogenic signalling. As you said, cancer cells can be targeted, but this is a problem as much as it is a solution. There is incredible genetic diversity (heterogeneity) found within a tumor, and when we specifically target aspects of these cells such as corrupted pathways using drugs or proteins coming from mutations with the immune system, this merely imposes a selection on the cancer as a whole. Our cancer drugs work, but not for very long. If we apply a drug that kills cancer cells with a specific mutation, you will see remission (the tumor shrinks due to cells dying), then it will stabilize, then it will regrow. This is because the drug you have applied killed those susceptible, but left behind those that weren't to continue to grow. In other words, the tumor as a whole evolved out of the treatment because there was so much genetic diversity, some of the cancer cells did not contain the target and continued to survive and reproduce. On top of that, we have recently discovered that there is a hierarchy of cells within cancer. Sitting at the top of this hierarchy are what are called Cancer Stem Cells (CSCs). These cells dedifferentiate back into a stem cell state that closely resembles a human embryo. In fact, the same transcription factors (Oct4, Sox2, Klf-4, c-Myc, etc) than enable totipotency and pluripotency in embryonic stem cells get reactivated in this tiny sub-population of cancer cells. On top of that, stem cells are critical to bodily function and are ridiculously hard to kill. These cells have replicative immortality, are incredibly immune priviledged, and also contain These pumps are critical, when nearly any drug enters the cytosol of CSCs, these pumps just pump it back out into the extracellular space. It has also been shown that radiotherapy can induce non-CSCs to transform into CSCs in some cancers. So as we target cancer with drugs that cause cell death, the remission we see is almost solely the non-CSC dying. In time, this important sub-population of CSCs that makes up around 2% of the population is selected for, and will grow to be about 20% of the cells within the tumor. Most cells in cancer are kind of just "bulk"; they will divide and contribute to the tumor, but eventually hit their hayflick number and are incapable of metastasis and tumorigenesis (forming new tumors around the body). What is absolutely critical to cancer therapy is identifying and finding ways to kill this population of CSCs that are responsible for almost the entire disease. They are immortalized, responsible for self-renewal, heavily resistant to cytotoxic therapy, and are the cells that undergo metastasis, leading to over 90% of the mortality of cancer. Find a way to destroy these cells and you will cure cancer.

[@kagaria]

@@brcarter1111 wow so complicated.

[@yvonnehyatt8353]

Study Bruce Lipton please thanks.

[@cheapmovies25]

If only we could develop a drug that could be a harmless protein or enzyme that could sit in blood and when a cancer only cell floats around it can render it harmless. That way once antumor develops it couldn't spread so it would help alot

[@davidcabrera2018]

My question is, what do cancer cells have in common? Why can't we target that weakness? Can we supply humans with stem cells to recover from good cells deficiency?

[@lucaspierce3328]

Peggy Zucerman you're absolutely right, immunotherapy is one of the most effective treatments to cancer I've researched so far.The thing is it utilizes the adaptability of immune cell's to specifically target the cancer in question, and it can be artificially selected to do so. Though I also research how cancer evolves, how it influences evolution, and how mostly benign tumors can contribute to morphological and developmental evolution, starting out as structural spandrels or non-functional cell masses simular to set-aside cells, and gain function it would have to be extremely modular at first, then is can acquire a new function by exploratory behaviour and phenotypic/genetic accommodation and other processes. Also adaptive anti-cancer selection can allow it to further, refine it's stability and integrative functionality within the organisms. Though anti-cancer selection is also related to selective canalisation which can never be perfect, thus there is always a potential of cancer in multicellular organisms. Cancer is predominantly caused by epigenetic changes and therefore is related to developmental plasticity, which is inherent in all living systems. In essence anti-cancer selection can never be 100%, in actuality it can constrain the generation of evolutionary developmental and morphological novelty. Many cancers may actually be an evolved response to massive physiological stress and toxin build-up, where it is overwhelmed by the levels of intra-organismal pollution and PH imbalance etc, again it would be variable as well, making it vulnerable to overfunction and dysfunctionality.

[@brcarter1111]

Our immune system works largely by differentiating between self and non-self. This is much more rational than being able to recognize every possible pathogen that exists in nature. One of the great mysteries in medicine is why our mothers immune systems don't kill us in utero. Having a 50% DNA contribution from our fathers, this DNA and the proteins it encodes should be regarded as non-self. To hide from this mechanism, embryonic cells display surface molecules that inactivate or even kill maternal immune cells. Many of these embryonic/fetal cells in cancer become reactivated, allowing cancer to be invisible or lethal to our immune system.

[@reginaldmcnab3265]

Very informative!

[@beautyofnature4280]

Superb

[@AnnuAparajita]

There is a statement here "Primary doesn't kill,metastasis does".How's that true?

[@Jarmo187]

When cancer spread to other organs, they fail. And that kills you

[@davidaustin6962]

+Annu Aparajita Yeah, he didn't talk about that enough. Here's what he should have said. The primary tumor is usually contained within a hard shell that you body creates against it. It is contained. Once that shell is broken, the cancer cells there are mature and are thereby far more dangerous than the original tumor was when it first started out as a minor malignancy, maybe even as a non-malignant growth, and ... and ... they are mobile and can start 100 new sites, whereas before you were only starting with 1, which was well contained. Also, the metastasis happens when you are older, and weaker, and they lodge in areas whose functions are more fragile. A tumor in the breast is not going to present as great of impedance to human functioning as the same tumor growing in the pancreas.

[@brcarter1111]

over 90% of cancer mortality is caused by metastasis. As he mentioned, some primary or even benign tumors can kill by exhibiting what is known as the mass effect. If a tumor mass forms in an important location such as the brain, intestines, or lungs, the mere mass of the tumor may begin to press on important organs and cause them to lose function by pressing on nerves or blocking passageways. Metastasis occurs when a small portion of the cells disseminate from the primary tumor, enter blood vessels or lymphatics (intravasate), circulate around and eventually leave the circulatory system (extravasate). How this process is occurring is not known. Once the cancer cells have left the blood supply and re-entered a distant tissue, they begin to proliferate and form a new tumor. This is analogous to seeds spreading in the wind. As more and more cancer cells develop, not only are they causing certain tissues to lose function, but they begin to act almost as a parasite. They create a massive metabolic drain by hogging up nutrients and blood sugar to fuel their proliferation, leading to a irreversible syndrome known as cachexia, or chronic wasting. As this condition worsens, the vital body functions that maintain homeostasis fail one by one.

[@benjooman1]

@@davidaustin6962 Yes, biopsies are DANGEROUS! NEVER TRY TO SECOND GUESS THE HUMAN BODY. There is a reason why the body encapsulates cancer cells in such a hard shelled tumour. Poke the tumor is inviting trouble. The more they study, the less they know. Do you think that the pik ribon people are interested in curing cancer? LOL

[@MichaelHarrisIreland]

Our efforts are looking primitive but no matter, all first efforts are.

[@garyordo5131]

I believe I said when our immune system becomes too deficient

[@insidejob2012]

He wears glasses, I believe him

[@KumariKumari-fw7nc]

???

[@sesaosalemh]

Human life is managed. Meaning that you do not control your cells or organs. However some one does. There is so much amazing synchrony. When some thing is out of place., You have no choice except to look for the power who has the control. Treatment and intervention will not be a substitute.

[@luxnox9303]

everyone has a plumbus in their home!

[@springteen3743]

Seems to me that cancer cells are part of our bodies as normal. Maybe is not a disease after all. There is got be a purpose for these cancer cells that want to feed and growth so diligently. Maybe scientists should find the reason why cancer cells exist and I also wonder if animals in the wild suffer from cancer cells.

[@KlecksBane]

Yes wild animals also suffer from cancer.

[@唬爛魚]

Fighting

[@whyaminoob]

we haven't cured it because CANCER is such a huge industry that is looking to expand. if they found a cure, what would happen to their market??????

[@someperson5506]

+vectireni But think about the individual scientists - how much would they do for a NOBEL PRIZE? That's worth more than any bribe!

[@juanibarra4123]

There are cures right now. Its just that they are being hushed. Watch The Truth About Cancer by Tai Bollinger. He also has a KZbin channel.

[@someperson5506]

+• Do rich, powerful people get cancer? Yes? Then there is no suppressed cure. If there were, they would've used it on themselves.

[@juanibarra4123]

+• $10k not $10

[@agumonkey]

+vectireni You mean BigPharma is a tumor ?

[@EssiacHempLaetrile]

Cannabis cures Cancer: "Cannabis Science Negotiates Several Commercialization Deals To Make Its Anti-Cancer Cannabis Formulations Available To The Public" Dr. Melamede, President & CEO, Cannabis Science / University of Colorado, Colorado Springs / Program Administrator, Phoenix Tears Foundation / Scientific Advisor, The Unconventional Foundation for Autism

[@emiliospowerballer1441]

cure to cancer exists, it just doesnt work all the time. ANYONE has a risk of getting cancer and usually cancer is specific from person to person because our bodies are different. im certain that certain people can endure cancer while others cant, which it depends on the individual. whats weird though are the stories we hear, like, someone is diagnosed with cancer has 6 months to live and within the 3rd moth cancer DISAPPEARS. how on earth does this happen? like, you just had cancer one day and right the next day it just DISAPPEARED? what kind of doctor did you have?

[@brcarter1111]

believe it or not, most oncologists believe microscopic tumors are forming in the body constantly. In a process called immunosurveillance, the immune system wipes them out before they progress and eventually become cancerous. If your interested in learning more, take a look at the MHC I pathway. You can find plenty of useful videos on youtube

[@bencyber8595]

what about work on " free from all sickness , disease " 🍍🌽 🥕

[@donaldgalindo8241]

The man

[@MrCannatopia]

No mention of cannabis, boo!!!

[@elizabethCorkins83]

🖤

[@aysegocer3308]

❤

[@fuzzyone99]

WTF is this supposed to be? Medical school?