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How to cure the cancers?

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Posted at 2013-10-2 07:44:30 | All floors |Read mode
Normal cells and cancer cells are twin brothers. Classical strategies target the different aspects between them, such as malignant proliferation and different protein markers. We all know these methods don’t work well, because the drugs which kill cancer cells can also bring huge side effects. Hundreds of people suffer from the aches and pains which come from these therapy ways. So can we really find the different points between normal cells and cancer cells? I’m not optimistic that these strategies could wipe out all of the cancers.
So can we choose another way to solve this? I’m not sure. But I think cancer cells are part of our bodies. Maybe every cell can be cancer cells under certain conditions just as iPS cells. Thus maybe every cancer cell can also be normal cells if we know the proliferation regulatory mechanism of our body. We may use drugs in a particular time and location to tell the cells you are normal.
What can we do first?

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Posted at 2013-10-4 03:01:23 | All floors
The transformation of normal cell to cancer cell is an accumulation of mutations and changes in metabolism.  The studies of p53 mutants show that normal cells in our body could tolerate high level of mutation without any phenotype.  Thus again, the question falls into the filtering of noise of gene expression and mutations.  I remember Prof.Hood from Institute for Systems Biology mentioned the reduction of noise when two blood samples were compared, we could go through his work to see what he did with those blood cells.

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you mean the cancer state might be reached by gene expression fluctuation?  Posted at 2013-10-4 08:00
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Posted at 2013-10-4 07:53:24 | All floors
That's a billion dollar question~
Actually, killing all cancer cells are really easy, just burn them....
In my opinion, one of the most important things in dealing with the cancer problem is to distinguish cancer cell from normal cell, and therefore specifically target cancer cell only. Due to that they were once a normal part of the body, even our immune system can't do it well. That's the major challenge in my mind.
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Posted at 2013-10-5 16:09:37 | All floors
Well I think the present scenario on treating cancer or developing cancer therapeutics isn't as bad as you think. The major focus of current cancer drug development is targeting signaling proteins, mostly kinases. These kinase inhibitors offer much better selectivity w/ significantly less side effects compared with traditional cytotoxic chemotherapeutics. Furthermore, many small molecule kinase inhibitors can be orally administered, which means some cancer patients can safely live @home. With these, several types of cancer are actually quite treatable, e.g. CML(philadelphia syndrome) by Abl kinase inhibitors, or  a subtype of melanoma by Raf kinase inhibitors (This type of cancer cells employs an overactive mutation of Raf, which is absent in normal cells. The first Raf-V600E inhibitor approved last year shows high selectivity toward the mutated kinase against the WT), among many others.

The major problem, though, I think lies in the rapid resistance often emerged with long-term drug administration. So as a side comment on your point, "wiping out cancer cells" is often not the ultimate goal in cancer therapy, lengthening the life of patients -- basically means delaying the onset of resistance in many cases -- is. There has been extensive research on how to achieve this, a recent interesting example is this: http://www.ncbi.nlm.nih.gov/pubmed/23302800

Though targeted cancer therapy may only work for a few types of cancers now, the "curable" types of cancers will expand fairly rapidly. So in my mind, the next paradigm of cancer therapy, is 1) carely categorization of patient cancer subtypes and stages, thereby determining which drugs might be effective; 2) administer the relevant drugs, once resitance emerged, switch to second-line therapies, with further resistance emerged, switch again. This may sound awkward, but without new insight (which maybe you guys coud provide), I think will be the dominating strategy in a foreseeable future.

A recommedable account of the history of cancer and the war on cancer is a recent Pulitzer-winner The emperor of all maladies, which offers juicy stories and real, interesting and quite readable science. The book has already been translated into Chinese, which I haven't read, but is quite well received by douban'ers.

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 Author| Posted at 2013-10-7 11:35:13 | All floors
nyin Posted at 2013-10-5 16:09
Well I think the present scenario on treating cancer or developing cancer therapeutics isn't as bad  ...

So please exactly tell me what kind of cancer can be cured? If someone you know gains what kind of cancer, you can easily tell him/ her 'you are ok'. Though the treatments of cancer develop very fast last decade, only a few cancer moralities decrease, like stomach cancer. Most of caners, such as lung cancer, breast cancer, pancreas cancer, ovary cancer, liver cancer and prostate cancer, still kill thousands of people every year according to the statistics of the American Cancer Society.
Also, can you tell me how many subtypes we could characterize a cancer? In what kind of criterion? I think the result is countless! Socan our therapy research could pursue the development of cancer subtype

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 Author| Posted at 2013-10-7 12:38:48 | All floors
I think the fisrt question should be 'the tumor comes from one cell or not?' In theory, one cell is enough to induce cancer. So what happened to this cell?

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Posted at 2013-10-7 14:00:06 | All floors
wuhongkun Posted at 2013-10-7 11:35
So please exactly tell me what kind of cancer can be cured? If someone you know gains what kind of ...

I'm for that cancer mortality is decreasing based on some data:

http://www.cancerprogress.net/overview.html

and a report from cancer society:
http://www.cancer.org/cancer/new ... -steadily-declining

It is ture that cancer is still a big problem, but appearently human are making progress especially on gene therapies towards breast cancer and leukemias

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Posted at 2013-10-7 18:49:49 | All floors
Last edited by nyin In 2013-10-7 21:01 Editor
wuhongkun Posted at 2013-10-7 11:35
So please exactly tell me what kind of cancer can be cured? If someone you know gains what kind of ...

1. The answer to the first question can be looked up in multiple sources. From what I'm aware of, besides the two examples I mentioned in my first reply, non-small cell lung cancer, gastrointestinal stromal tumor, certain subtypes of breast cancer, among many others can be treated by targeted therapy. (Which, as I said, offer good selectivity and less toxicity.)
2. I do have close relatives suffering from cancer, which I don't think is a 'gain', but she is recovering well after chemotherapy and radiotherapy.

3. I'm not saying we have cured cancer, or even we are on the right track, but we're definitely making progress. As pointed out by @aruonijiao, alternative therapy such as gene therapy, immunotherapy, etc. also surge with rapid progress in recent years.

4. I think subtyping cancer is a big field on its own, which I've only shallow ideas. Testing the existence of different biomarkers is something I can think of. Two examples related to my examples CML and melonoma, Gleevec cures patients with philadelphia chromosome, while Vemurafenib cures melanoma with V600E BRAF mutations. This two genetic signitures can serve as both disease & therapy markers.

Thinking of cancer as ONE disease is an ALLURING idea, especially welcome in my physics-minded friends. (Also by James Watson -- he firstly pursued the idea that cancer is caused by viruses, afterwards considered restricting angiogenesis as the ultimate cancer cure.) The next natural step is to think that there could be a universal treatment strategy for all cancers. My current naive thinking is that this is a beatiful trap. We have ~30000 genes, as a further question following yours, how many ways could a cell with 30000 genes go wrong into cancerous state? I would say the number of possible ways (aka subtypes of cancer) is huge but not countless. (I have no evidence on this and  would love to know an answer). Cancer is a group of diseases sharing several common features, but despite highly toxic non-selective chemo/radio-therapy, each subtype of cancer may require carefully tailored killers. That's a long way to go definitely, but what interest is there if we can see through the end now? (Please don't call me cold-blooded :p)

An example: certain breast or prostate cancers can be cured by hormone deprivation, or hormone receptor antagonists. What does it mean? It means even in cancerous state, these cells from sex organs still have their identity buried in them -- they still need hormones to thrive. I think this is one thing that distinguish cancer cells from stem cells.

*disclaimer* I'm not a cancer researcher, these ideas come from my very limited literature readings.  I appreciate any critics and/or improvements.

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Posted at 2013-10-7 22:08:39 | All floors
Last edited by jyuan In 2013-10-7 22:11 Editor

Firstly, it has been

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Posted at 2013-10-7 22:08:53 | All floors
Last edited by jyuan In 2013-10-7 22:12 Editor

Firstly, it has been a long debating question whether cancer cells have properties like iPS cells. Secondly, the side effects of the current drugs are not the main reason we cannot kill the cancer cells. It is the cell resistance to drugs that induce cancer cell prolifaration and cancer recerrence, at least during recent years. Last but not least, gene mutations like RAS have crucial effects during target therapy, so it is important to study this topic in the gene level.

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Posted at 2013-10-10 13:39:33 | All floors
nyin Posted at 2013-10-5 16:09
Well I think the present scenario on treating cancer or developing cancer therapeutics isn't as bad  ...

Agree. But addition to the drug resistance, I have some other view on the difficulties of treating cancers tumor cell proliferate, evolves and develop the resistance to whatever drug people used to kill them. However, the property of "proliferate, mutate and evolve" happens for all virus and bacterias that infect human. Nevertheless, flu does not kill us.  Most of these pathogens are far less harmful than cancers.

Trade-off between virulence(the ability to kill host) and transmission is one possible answer for the "nicer" pathogens: if they kill the host too fast, they can't spread among the population. So "smart" virus and bacterias does not kill like cancer. On the other hand, tumor cells in general don't transmit from one person to another , so they didn't learn how to play nicely.

There are exceptions. Two kinds of tumor cells can be infectious between individuals in dogs and devils. (http://en.wikipedia.org/wiki/Clonally_transmissible_cancer)
(http://en.wikipedia.org/wiki/Devil_facial_tumour_disease)

Interestingly, while the dog tumor has been around for hundreds of years and become something very mild (not kill the infected dog), the devil tumor just appear for tens of years and is very aggressive (transmit through biting and kill the infected devil). It is basically driving the devil into distinction.
I think one can study these tumors to learn how to force cancer cells play as nice as flu.


Here is a proposal I once write for answering this question using in-silico evolution, if someone feel interested:



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 Author| Posted at 2013-10-10 16:00:16 | All floors
aruonijiao Posted at 2013-10-7 14:00
I'm for that cancer mortality is decreasing based on some data:

http://www.cancerprogress.net/ov ...

First, I admit that we humans have already invented some effictive methods to help people.
Then, We both know the war against cancer will never end.

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 Author| Posted at 2013-10-10 18:44:30 | All floors
nyin Posted at 2013-10-7 18:49
1. The answer to the first question can be looked up in multiple sources. From what I'm aware of, b ...

1. Even at the IA stage, 5-year survival rate of non-small cell lung cancer is 49%
http://www.cancer.org/acs/groups/cid/documents/webcontent/003115-pdf.pdf
Based on people treated between 1992 and 2000, the overall relative 5-year survival rate of people diagnosed with a malignant GIST was estimated to be about 45%.
http://www.cancer.org/acs/groups/cid/documents/webcontent/003103-pdf.pdf
...
2. Sorry for my previous improper words. My grandma died from stomach cancer, so we should know that current therapy in China or in the world cannot be suitable for everyone.
What in my mind is traditional antagonist hardly overcome its side effect. Unlike other disease, the characteristics of cancer defined by Robert A. Weinberg et al are Self-Sufficiency in Growth Signals, Insensitivity to Antigrowth Signals, Resisting Cell Death, Limitless Replicative Potential, Sustained Angiogenesis, Tissue Invasion and Metastasis, Avoiding Immune Destruction, Tumor Promotion Inflammation, Deregulating Cellular Energetics and Genome Instability and Mutation. Even without the outside stimulation, spontaneous cancer still exists. Unlike well-controlled development, the cancer is a part of our life which is chaos and disorder. What happens to the cell which can escape from cell junction and the monitoring of our immune system? Is there existing a random common bug which overlooked by its own repair system.
We need novel ideas.
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