Watson on Cancer and Antioxidants

James Watson argues that cancer researchers should focus on anti-antioxidants.

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Watson was relevant once; no

Watson was relevant once; no more.

That is rather ungracious

That is rather ungracious kayaker; nevertheless, it is true that Watson is not distinguishing between possible value in intefereing with the original genesis of cancer and intefereing with the treatment of cancer once extant.

But the most charming thing about the episode is how the advice seemingly contradicts the late career pasion of another brilliant Nobel laureate, Linus Pauling. But those two gentlemen argued over the structure of DNA too.

There is a concept of

There is a concept of metahormesis in which it is posited that even under normal physiologic conditions (no reference to cancer or chemotherapy), reactive oxygen species are an important signaling molecule for activating endogenous pathways that produce antioxidants such as glutathione. Allowing for and maintaining low-level ROS present in mitochondria for example may be protective because they keep these pathways "pre-conditioned" or "primed" so that when there is a significant oxidant stress or exposure, these pathways may be up-regulated as a form of "rapid response." By taking excessive amounts of dietary antioxidant supplements, we may be quenching ROS levels to such a low level that they are not present to function as signaling molecules that activate endogenous protective antioxidant pathways through a master regulatory protein such as Sirtuin1 (SIRT1). Ironically and counter-intuitively, too much antioxidant therapy may lead to an inactive state for these endogenous pathways, so that damage to mitochondrial DNA, proteins and other biomolecules occurs in the setting of high-level oxidative stress and production of harmfully high levels of ROS. In this scenario, endogenous protective pathways are not "primed" to respond quickly enough to prevent such damage. This may explain the results of at least one large retrospective study that found an association between 800 IU of dietary vitamin E (an antioxidant) and an increase in all cause mortality as compared to the recommended 400 IU daily. We seem to be an "over the top" society in which a little bit of scientific knowledge can be dangerous. If 400 IU of vitamin E is good for you, then 800 IU or 1200 IU units must be even better. And there is no limit to how much vitamin C (a favorite of Linus Pauling) is beneficial in large daily doses. Given the above and now referring back to Dr. Watson's statement that dietary intake of antioxidants may be "hampering otherwise effective oxidative therapies" for cancer chemotherapy, I believe there is good evidence that suggests that the quantity and context of dietary intake of antioxidants may determine whether the effect is protective or harmful. And as a side note, I consider James Watson and Linus Pauling luminaries during the height of their scientific efforts and as thought leaders thereafter. Admittedly, Dr. Pauling's obsession with vitamin C is likely ultimately misguided. Let's please have respect for the scientific legacy that we all aspire to continue.

I agree that Kayaker's single

I agree that Kayaker's single line comment is ungracious. I would add that it is in poor taste, uninformed and inelegant. The problem with blogs is that anyone can say anything in anonymity and without much forethought. But then again, freedom of speech is exactly that. Everyone has the freedom to express their opinion. Not so in many non-democratic countries. But I think we can express our opinion (not truth) in a constructive and collegial manner. Simply making that one line caustic and critical statement contributes nothing to this blog except to provide an example of the abuse of free speech.

It's time to understand there

It's time to understand there are only 2 approaches to treat and cure cancer,namely, biotherapy (Bert Vogestein is pursuing this) and combined gene therapy with cancer causing genes; one delivered and expressed in cancer stem cells, the other expressed in HSC to activate the immune system as suggested by myself in 2010. Michael Lerman, M.D., Ph.D.

Dr. Lerman, I "grew" up

Dr. Lerman, I "grew" up reading the work of Kinzler and Vogelstein (the dynamic duo) and many other great cancer biologists. And of course I am familiar with your ground-breaking work in immunotherapy. What is troubling to me when we talk about cancer cure is that in every case in which a therapeutic approach has been developed that induces a therapeutic response or "cure," resistance has developed through escape routes that cancer cells often develop if any survive the initial therapy. Combination chemotherapy was a paradigm for using different classes of cancer chemotherapeutic drugs to prevent resistance (or multi-drug resistance). But even this has not been the solution. Another example comes to mind. When androgen-ablation therapy is used to treat metastatic prostate cancer, it is considered palliative. Why? Because nearly 100% respond initially and nearly 100% relapse. The prostate cancer cells find some way of producing androgen to reactivate the androgen receptor pathway or they use other escape routes. Why will immunotherapy as proposed by Dr. Vogelstein and yourself be the exception and be immune (no pun intended) to the eventual development of resistance and therefore the failure to ultimately achieve cure? My skepticism (more like curiosity actually) may be related to the fact that I was a pre-doctoral student with Dr. Susan Horwitz, whose group developed bleomycin and taxol and studied the multi-drug resistance phenotype for decades. When I was in Susan's lab, we were still getting Taxol from the bark of the North Western Yew tree. I think an entire forest was grown in Oregon to supply taxol for pre-clinical studies and then clinical therapy until the de novo synthesis of the taxane ring was achieved and all of the derivatives of taxol currently used were synthesized and developed as a novel class of chemotherapeutic drugs. I eventually trained in nephrology and not oncology, so what do I know? Only that the treatment and cure of cancer will need a radical new approach if we are ever to be able to say that "the" cure for cancer (all cancer) has been achieved. And I am not sure that will ever happen because cancer cells are by nature highly prone to the development of resistance through a higher rate of mutations and higher likelihood of activating an escape route.
Stephen Hsu, MD, PhD

Dr. Hsu, What would the

Dr. Hsu,

What would the "radical new approach to treatment and cure of cancer" look like?
Adding to what you say, isn't there a realization setting in that medical research will for the foreseeable future chase one step behind cancers which evade the treatment pressure with mutations? There are some impressive, highly publicized examples of successful, targeted cancer treatments which address cancers caused by single genes, but the majority of cancers are not that simple. Is the public being misled that we are in the process of winning the war on cancer with those new smart diagnostic tools combined with targeted approaches, e.g. Antibody-Drug-Conjugates?
With the emergence of microbiome research, an additional layer of complexity becomes apparent in that not only the human genome but also the microbial community in the human body contributes to the regulation of the immune system which can cause all kinds of diseases and possibly also cancer.
Can the body heal itself? What is your opinion of approaches such as the Gerson Therapy which uses liver detoxification combined with hightest doses of plant enzymes (through ingestion of huge amounts of vegetable juices and selected supplements) to enable the body to heal itself and to fight the cancer?? - A holistic solution or quackery?? Thanks.

Thank you for your insightful

Thank you for your insightful questions. I will try to provide a meaningful response by telling you about my own family experience of cancer. My uncle recently died of metastatic pancreatic cancer that was diagnosed too late to undergo surgical resection aiming for cure. So, he was started on chemotherapy, his only other therapeutic option, although I believe strongly that treating the mind/body/spirit (view from the east) or attending to the biopsychosocial dimensions of the human person (just a western rephrasing of the same eastern philosophy)--ultimately contributes to and should be an integral part of the overall therapeutic plan. So, there is a role for art therapy (music, dance, painting) and Tai Chi and guided imagery and yoga along with an appropriate diet. So, in general, I do subscribe to the holistic approach, although I can't comment specifically about Gerson Therapy. I also believe that physicians should take every opportunity to invoke the "placebo effect" by developing a trusting relationship with the patient, by sitting on the bed, by holding the patients hand and forehead and doing a thorough physical exam (much of this lost now in the age of advanced medical technology; just do the "pan-scan" and treat the numbers). The placebo effect has been documented to contribute as much as one-third of the therapeutic efficacy or response. If we don't leverage on the placebo-effect, which likely reflects activation, at least in part, of the immune system, we lose the opportunity to help the body contribute to healing. So, yes, I believe that the body can contribute to healing in this multi-modality approach.

Back to my uncle. When he contacted me about his diagnosis, I arranged for his repeat work up and therapeutic plan with one of the leading experts in pancreatic cancer at an NCI (National Cancer Center) designated Center of Excellence. The work up confirmed that he had stage 4 disseminated panceratic cancer. At age 70, he had to decide between quality of life and quantity (duration of life) in choosing several options for combination chemotherapy. He took the middle path and did well for some time, was able to travel back to his home city in Taiwan to visit with friends and family. And he received outstanding and timely care, which was eventually transferred to a GI oncology group at another outstanding cancer center on the west coast so that he could be near his sons and his only grandchild.

As we were waiting for his first visit to see the oncologist who specialized in the treatment of pancreatic cancer we watched the news about the death of Steve Jobs from a rare cancer of pancreatic origin, insulinoma. My uncle joked that although he had not created anything that fundamentally changed the way that we live and work and learn and play, he and Steve Jobs had something in common--pancreatic cancer. And he knew the story of how Steve Jobs had battled cancer for a long time, going from one treatment to another from country to country if necessary to prolong his life. He asked me what I thought about chemotherapy. I told him that in my experience taking care of adults with cancer, "The longer you live, the longer you live." By that I meant to convey that you should not waste a day if possible to initiate some form of therapy that will prolong your life--long enough that when the specific therapy (chemotherapy, immunotherapy, etc.) becomes ineffective due to resistance, there may be a new treatment with a different mechanism of action that he can try with the hope that he could achieve remission again until the next relapse.

So, the longer he could live a reasonable quality of life, the more likely a new cancer therapy would become available that could buy him more time--time to see his grandchild grow up. So, "the longer you live, the longer you live" -- the best case scenario that I could relay to him. But the problem is that all cancer therapies have associated side effects and toxicities. And the likelihood of dying from a complication of therapy is high. My uncle's chemotherapy regimen eventually became ineffective, as evidenced by imaging studies and a rise in a classic tumor marker on blood testing. He was just about to switch to a new therapy the next week, when he unexpectedly experienced extreme fatigue. He went to rest in bed, likely had altered mental status and could not protect his airway. He went into acute respiratory distress and was rushed to the ICU where he was intubated and sedated for presumed aspiration chemical pneumonitis/pneumonia. He died two days later when his eldest son (my cousin) withdrew extraordinary measures when it was clear that he was developing multi-organ system failure in addition to respiratory failure (hypotension, kidney failure, liver failure). My role in all of this was to help him to die well at the completion of his normal human life cycle. I made sure that he died with dignity, comfort and the presence of his loved ones. There is a seasonality to our lives. He had reached the last winter of his life and spring would never come again.

Breast cancer is one of the

Breast cancer is one of the common women health issue in many countries and for thar Breast Cancer Action is one of the long-time partner of Women’s Cancer Action which has currently released their Screening Recommendations and Policy to offer suggestions to women on how to make informed decisions about screening. Like that there are number of issues of breast cancer are growing day by day.

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Dr. Hsu, Thank you for

Dr. Hsu,
Thank you for sharing your beautiful and eloquent account of your Uncle's cancer.
Also to you and Dr. Lerman for an extremely interesting debate which expanded my knowledge and curiosity greatly.
Was all this in provocation or in spite of the original "ungracious, poor taste, uninformed and inelegant" comment as you put it?
Regardless, it was a reminder that this form of communication has great merit for me at least.
Sincerely,

paul scott