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Irritating comment by Larry Page


Tridimity

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He said he found it surprising that finding a cure for cancer would only add three years to average life expectancy.

"When you really take a step back and look at it, yeah, there are many, many tragic cases of cancer, and it's very, very sad - but in the aggregate, it's not as big an advance as you might think."

 

 

I appreciate that, on the whole, a universal cure for cancer would not actually extend the average lifespan by very much - precisely because age is a risk factor for the development of cancer. Acquiring the suite of mutations and number of cell doublings implicated in cancer - not to mention the development of anti-apoptotic, invasive and metastatic phenotypes in cancer cells - takes decades usually. But to claim that, 'in the aggregate, it's not as big an advance as you might think.' Really? Is this guy in his right mind? I can only assume that he has never witnessed the protracted death of a loved one to this disease; has never witnessed their intense physical discomfort and pain and the psychological and emotional impact on both the patient and their family and friends. It's not all about how long you ward off death - it's also about the way in which you die.

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It's not all about how long you ward off death - it's also about the way in which you die.

 

This is quite an important point. But how about (more or less speculative) treatments that are not aimed at treating cancer, but improve its management and life quality until it overwhelms the system?

One issue with cancer treatments is that while they may prolong the life of the patient to some extent, they are also very destructive of the body and can be even more painful than cancer itself (depending on a lot of parameters, of course). In other words, the treatment does not automatically improve life quality, aggressive chemos do quite the reverse in fact.

 

In that context would better management be preferable over treatment?

 

Edit: I should add that one could and probably split it further up as it will of course be highly dependent on the type of cancer and at which age it has been acquired. But for discussion's sake I will keep it as general as OP.

Edited by CharonY
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I think it would be more than 3 years anyways. There are a number of longevity techniques we can't use presently, because they stand a good chance of causing cancer themselves.

 

Like telomere lengthening?

 

 

This is quite an important point. But how about (more or less speculative) treatments that are not aimed at treating cancer, but improve its management and life quality until it overwhelms the system?

One issue with cancer treatments is that while they may prolong the life of the patient to some extent, they are also very destructive of the body and can be even more painful than cancer itself (depending on a lot of parameters, of course). In other words, the treatment does not automatically improve life quality, aggressive chemos do quite the reverse in fact.

 

In that context would better management be preferable over treatment?

 

Edit: I should add that one could and probably split it further up as it will of course be highly dependent on the type of cancer and at which age it has been acquired. But for discussion's sake I will keep it as general as OP.

 

I agree that traditional treatments for cancer (surgery, radiation therapy and classic chemotherapies) are too crude, ineffective and pose too many long- and short- term side effects including, in some cases, infertility. For these reasons we urgently require more rationally-designed drugs - selective inhibitors of oncoproteins and agents that promote tumour suppressor function - for the treatment of different cancer types. Some of these are finally trickling down from big pharma but, even so, on the whole they only extend lifespan by a few months to a couple of years at most. Whether or not they improve quality of life during this time is questionable. Such agents need to be used in combination on the basis of the unique genetic and proteomic profile of the individual patient's cancer (personalised medicine). I would argue that even this is not quite enough and that what will ultimately help to defeat cancer to the point of reliable functional cure, is to generate molecular profiles of cells from many different parts of the tumour or metastases and from the surrounding tissues - on a single-cell basis - so that the variability between individual cells in a tumour is not ignored. It is not acceptable to perform a Western on tissue derived from one area of the tumour and to claim that the observed protein levels are representative of each of the individual cells within the tumour. Since tumours develop as a series of clonal expansions, to ignore the details of between-cell variability is to grant the minority of cells that have the biological capacity to resist any rationally-designed monotherapy, the chance to do so and to permit relapse.

 

Improved management of the care of cancer patients is, of course, always desirable. How would this be achieved, where is there room for improvement? Any physician worth her or his salt will already present patients with the array of options that they have in deciding on an appropriate cancer treatment regimen. This will depend very much so on the priorities of the patient: are they willing to tolerate the side-effects of treatment for the sake of an additional year's survival? Perhaps there is some very special event that is of great personal importance to them and which they wish to attend before they die - the birth of a family member, a marriage - or maybe they just want to see the sun rise in its chariot of gold 365 more dawns? For others, the side-effects of treatment may be deemed too physically challenging for the patient and too psychologically and emotionally distressing for the patient and their loved ones. One area of management that, I think, could certainly use immediate improvement is the provision of effective counselling services for the patient and their family and friends. Earlier detection would also help in identifying tumours before they have become invasive and metastatic - and before they have become more resistant to currently available chemotherapies.

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That, generalized treatment at the DNA/RNA level, and overhauling Mitochondria.

 

Calorie restriction is one method we could use today. Can cause significant health and wellness issues though.

 

Tumour cells tend to shut down mitochondria, the sites of oxidative phosphorylation and the intrinsic pathway of apoptosis. The former is beneficial for the transformed cell because, typically, the cells in the interior of a tumour will be experiencing conditions of hypoxia (even if the tumour cells have induced an angiogenic response, the resulting blood-vessels tend to be rudimentary, leaky and disorganised with many dead-ends) and so it is preferable for them to rely on Oxygen*-independent substrate level glycolysis as a means of generating ATP (even if the energy yield is less than the output of the citric acid cycle and oxidative phosphorylation). The pyruvate generated from glycolysis is often shunted into the lactate dehydrogenase-catalysed production of lactate, rather than into the pyruvate dehydrogenase-catalysed production of acetyl CoA for entry into the citric acid cycle. The lactate is then extruded by transformed cells to be taken up and used by respiring stromal or tumour cells, thereby saving glucose for use by hypoxic tumour cells. The latter is, of course, beneficial as it allows tumour cells to survive even in the presence of signals that would ordinarily seal their demise.

 

It has also been suggested that the use of a ketogenic (low carbohydrate, high fat - medium chain triglyceride) diet may be beneficial for cancer patients, since the diet relies on the consumption of food that does not increase plasma glucose levels, but produces ketone bodies (D-3-hydroxybutyrate, acetoacetate and acetone) that can be used as a Carbon* source for energy production. These bypass glycolysis and are metabolised by mitochondria in the presence of Oxygen*. Normal cells can adapt to using ketone bodies to produce ATP but tumour cells rely on high glycolytic flux and so would not be expected to survive on this alternative fuel source. Some in vivo and clinical studies have reported decreased tumour growth - even in cachexic patients, however a different study has reported negative results.

 

 

*Out of a mark of respect for the chemical elements, I like to capitalise the first letter of their names, have done so since I was 11 and not about to stop now. I hope that this is not too disconcerting for readers.

Edited by Tridimity
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Tumour cells tend to shut down mitochondria, the sites of oxidative phosphorylation and the intrinsic pathway of apoptosis. The former is beneficial for the transformed cell because, typically, the cells in the interior of a tumour will be experiencing conditions of hypoxia (even if the tumour cells have induced an angiogenic response, the resulting blood-vessels tend to be rudimentary, leaky and disorganised with many dead-ends) and so it is preferable for them to rely on Oxygen*-independent substrate level glycolysis as a means of generating ATP (even if the energy yield is less than the output of the citric acid cycle and oxidative phosphorylation). The pyruvate generated from glycolysis is often shunted into the lactate dehydrogenase-catalysed production of lactate, rather than into the pyruvate dehydrogenase-catalysed production of acetyl CoA for entry into the citric acid cycle. The lactate is then extruded by transformed cells to be taken up and used by respiring stromal or tumour cells, thereby saving glucose for use by hypoxic tumour cells. The latter is, of course, beneficial as it allows tumour cells to survive even in the presence of signals that would ordinarily seal their demise.

 

It has also been suggested that the use of a ketogenic (low carbohydrate, high fat - medium chain triglyceride) diet may be beneficial for cancer patients, since the diet relies on the consumption of food that does not increase plasma glucose levels, but produces ketone bodies (D-3-hydroxybutyrate, acetoacetate and acetone) that can be used as a Carbon* source for energy production. These bypass glycolysis and are metabolised by mitochondria in the presence of Oxygen*. Normal cells can adapt to using ketone bodies to produce ATP but tumour cells rely on high glycolytic flux and so would not be expectedto survive on this alternative fuel source. Some in vivo and clinical studies have reported decreased tumour growth - even in cachexic patients, however a different study has reported negative results.

 

 

*Out of a mark of respect for the chemical elements, I like to capitalise the first letter of their names, have done so since I was 11 and not about to stop now. I hope that this is not too disconcerting for readers.

 

 

Makes sense. Hadn't looked at them from that angle before though.

 

Mainly concerned about them leading to the death of healthy cells under low oxygen conditions. Would save a number of lives if we could alter their code. Just need to be free to do so without concern for causing cancer ourselves or giving cancer an edge.

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Such agents need to be used in combination on the basis of the unique genetic and proteomic profile of the individual patient's cancer (personalised medicine). I would argue that even this is not quite enough and that what will ultimately help to defeat cancer to the point of reliable functional cure, is to generate molecular profiles of cells from many different parts of the tumour or metastases and from the surrounding tissues - on a single-cell basis - so that the variability between individual cells in a tumour is not ignored.

 

 

You are preaching to the choir here. Quiote a bit of my work is in the area of proteomics and single cell analysis and there is quite a lot of things going on that are hard to interpret. I am convinced that more fundamental cellular research is necessary before we can properly interpret and intervene in cancer processes. Unfortunately the funding agencies are more focused on the applied side. At least hypoxia investigations have gotten some traction lately, but I feel a more integrative approach is needed. That is probably quite a different discussion, however.

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Context? Medically, curing cancer would be a huge advancement, but knowing that Google has launched a project to extend the human lifespan, curing cancer would not be as huge an advancement toward that particular goal as most people would probably think. In the context of that project, he's correct.

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Context? Medically, curing cancer would be a huge advancement, but knowing that Google has launched a project to extend the human lifespan, curing cancer would not be as huge an advancement toward that particular goal as most people would probably think. In the context of that project, he's correct.

 

I can see your point, in that he is estimating advancement in terms of longevity, independent of end-of-life experience. However, I do not think that longevity is the sole criterion on which Larry is basing his estimation.

 

there are many, many tragic cases of cancer, and it's very, very sad - but in the aggregate, it's not as big an advance as you might think

 

 

It depends on what he is referring to when he speaks of the tragedy of cancer cases and the emotional consequences of such cases. Perhaps, in this context, you are correct and he is referring only to the shortening of lifespan of these patients. But then, that would apply to all modes of death, including choking on peanuts. I suspect, however, that he is referring to the nature of the patients' deaths; the associated physical pain for the patient and the emotional turmoil for not only the patient but their loved ones also. Essentially, I think he is saying that when the lifespan/end-of-life experience balance is considered objectively, that the gains to be made from developing a universal cure for cancer are not as beneficial as one might think.

 

Frankly I am too pissed off with seeing people I care for die way before their time and in such a horrible way to buy into Larry's argument.

Edited by Tridimity
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I can see your point, in that he is estimating advancement in terms of longevity, independent of end-of-life experience. However, I do not think that longevity is the sole criterion on which Larry is basing his estimation.

 

 

It depends on what he is referring to when he speaks of the tragedy of cancer cases and the emotional consequences of such cases. Perhaps, in this context, you are correct and he is referring only to the shortening of lifespan of these patients. But then, that would apply to all modes of death, including choking on peanuts. I suspect, however, that he is referring to the nature of the patients' deaths; the associated physical pain for the patient and the emotional turmoil for not only the patient but their loved ones also. Essentially, I think he is saying that when the lifespan/end-of-life experience balance is considered objectively, that the gains to be made from developing a universal cure for cancer are not as beneficial as one might think.

 

Frankly I am too pissed off with seeing people I care for die way before their time and in such a horrible way to buy into Larry's argument.

That's why I was asking for the context of the quote, because considering Google's new focus on extending the human lifespan, I assumed it was in relation to that venture and didn't read it the way you seem to be doing.

 

Cancer is something of a looming specter associated with death by most people, for good reason as so many people are affected by it directly of indirectly over the course of their lives. Google launches a project to extend the human lifespan and I guarantee they get asked "are you going to work on curing cancer?" a lot. The answer is that, while cancer is horrible and curing it would certainly help a lot of people, it wouldn't extend the average human lifespan by nearly as much as most people think, which is the focus of Google's particular project.

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Perhaps, then, Google ought to change the objective of their project to not merely expand lifespan but to extend healthspan and to reduce human suffering as far as possible. Cancer causes an almost disproportionate level of human suffering, given its modest effects on average longevity, when compared with almost all other ways of dying. Few other deaths are so protracted and inevitable while being so physically and emotionally destructive. At least death by myocardial infarction or as a result of injuries sustained in a car crash, while still acutely painful, are likely to be fairly instantaneous - there is no prolonged psychological distress. In contrast, terminally ill cancer patients effectively have a death sentence hanging over them. Even if they do attempt to appreciate the brief time they do have left, they have to find new ways each day of coping with the knowledge of their own mortality and have to see their loved ones suffering on their behalf.

Edited by Tridimity
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I think dementia (and their causes) should go high on that list, too. Especially if friends and family is involved it is in some ways worse than cancer. At least in the latter case the person you know and love is still there to the end.

And it is really bad when the person has moments of clarity and realizes his/her situation.

Edited by CharonY
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