Monday 23 July 2018

abcam Cancer and Metabolism Conference 2018- 1/3

I recently attended abcam’s Cancer and Metabolism conference in Cambridge and realise that I haven’t written about it yet. 


In a nutshell, the event covered major aspects of metabolic transformation in cancer and attempted to highlight potential therapeutic approaches to target cancer-specific metabolic pathways. The conference allowed me to build on my existing knowledge of metabolism and metabolic signalling in cancer and introduced me to more advanced concepts, novel methods, and emerging technologies to target these pathways.

I was also introduced to a collaborative European wide research project called TRANSMIT: Translating the role of Mitochondria in Tumorigenesis. 

The angle they are taking with TRANSMIT is viewing cancer as not only a genetic, but also a metabolic disease. 

TRANSMIT Project- https://www.transmit-project.eu

Personally I think it is a metabolic disease with metabolic solutions and the genetic mutations are as a result of mitochondrial dysfunction. With healthy mitochondria it is my belief that you simply do not get cancer. However… whether it is cause or effect, the focus on cancer metabolism is a huge step in the right direction for me and I am greatly encouraged by seeing this type of event take place and to be able to have these conversations. 

The research I came across at this conference was all work that could directly be translated to the patient (‘from bench to bedside’) so I found this more engaging than most conferences I have been to. 

More and more now scientists are not only investigating the conribution of oncogenes and tumour suppressor genes (an approach which, as the primary focus over the years has been woefully ineffective), but we are also focusing on the intricate metabolic plasticity that transformed cells undergo to survive the adverse, volatile tumour microenvironment conditions. 

The mitochondria is the star player here, and rightly so, because they act as key players in cancer metabolic restructuring due to their crucial role in powering all functions of the cell by producing complex molecules for function, growth and survival. When these normal processes become aberrant, causing dysfunction, as is the case with cancer, this biosynthetic powerhouse of the cell is forced to adapt through more anaerobic respiration, and so is forced to provide energy and metabolites to the cell in different ways. 

These cells are very clever and can learn how to survive by using different substrates to stay alive and will become more resiliant with time if provided with the fuel that it needs to thrive. It will then become more able to use alternative substrates for energy as it adapts and learns, and here we have parallels with Darwinian biology. In the absence of nutrients, cancer cells can even scavenge from cellular debris in a process called ‘macropinocytosis’, so this is worth considering with any metabolic therapy, most likely it seems when necrotic tissue is a hallmark of disease as it often is with glioblastoma. That’s my opinion anyway, seems to make sense. Cancer doesn’t want to die, as a result of these metabolic abnormalities we have an occurance of mutations in metabolic enzymes encoded by both nuclear and mitochondrial DNA. 

It is my belief therefore, that more solid tumours would be most responsive to any kind of metabolic approach, as they have clear margins, are less diffuse and invasive, and as such have likely not yet progressed to being able to use multiple substrates to become more resilient to targeted metabolic therapies. More aggressive malignancies will likely require a combination approach of dietary manipulation and drugs targetting key metabolic targets in line with what the tumour’s metabolic signature may dictate. 

Electron microscopy morphology of the mitochondrial network
in gliomas and their vascular microenvironment-
https://www.sciencedirect.com/science/article/pii/S0005272810007437


As I began listening to the talks, the main research challenges became eminently clear. 

Firstly, we need to continue to learn about the bioenergetic plasticity of cancer in general. We have established that mitochondrial function and respiration play fundamental roles in the development and progression of cancer. The main challenges here are noted below numerically and although of major importance as a primary substrate for most cancers, its not all about the glucose:

1. Many malignancies have been shown to be able to utilise not only glucose, but also glutamine for generating cellular energy and provide metabolic building blocks to proliferate.

2. As stated, many cancers generate most of their cellular energy via mitochondrial respiration and oxidative phosphorylation (OxPhos). Glutamine is the preferred substrate for OxPhos in tumour cells.

3. Cancer cells are remarkably adaptable at using different substrates for fuel. They can even use metabolic substrates donated by ‘stromal cells’ for cellular energy generation via OxPhos. Stromal cells are present in the tumour microenvironment and are not necessarily malignant themselves but can provide the tumour with substrates it needs to keep growing.

4. Bioenergetic plasticity of cancer is a major consideration if we want to attempt to predict, understand and monitor a metabolic approach to treating cancer more effectively.

See below a poster displaying an outline of the work various research groups are undertaking as part of the TRANSMIT project:



How might we achieve this:

1. By targeting metabolic enzymes and coenzymes

2. Learning more about metabolic features of cancer cells in general. This can help us with therapeutic efficacy testing and biomarker discovery. 


Primary aims that I could see from this research:

1. Help to overcome chemoresistance

2. Come up with metabolic intervention strategies. 

3. Better understand the role of the mitochondria in cancer initiation and progression. 

4. Understanding of metabolic signatures of tumours that may respond to the ketogenic diet or specific nutrient deprivation diets. 


Dietary and drug strategies covered:

1. An energy restricted ketogenic diet. (high fat, low carb, adequate protein)

Most cancer cells thrive on glucose as major energy source and partly posess dysfunctional mitochondria leading to a reduced ability to metabolise fat. This approach is being studied as an adjunct to the standard of care. It may reduce tumour growth and prolong survival. 

2. Amino acid deprivation diets.

- Glutamine (protein restriction, temporary inhibition of enzymes involed likely more suitable)
- Methionine, cysteine

3. Fasting and diets that mimic a fasted state.

4. Drugs and drug targets

- Glutaminase inhibitors as a major target for the majority of cancers. For brain cancer perhaps more important in neuroblastoma (considered a real glutamine hog) and tumours that use up glutamine as the primary or major fuel alongside glucose as major substrates.

- Tryptophan degrading enzymes (overcoming tumour immune resistance)

- Citrin blockers- citrin is upregulated in multiple cancers.

- Targeting other novel metabolic pathways (aspartate, folate, serine, sapienate)

- Dichloroacetate (DCA)- PDK inhibitor (Pyruvate dehydrogenase kinase)- mitochondrial enzyme activated in a variety of cancers. Pyrimidine biosynthesis and growth of SDH (Succinate dehydrogenase) deficient cells is also inhibited by this drug.

- Biguanides and Kinase Inhibitors (KI)- induce opposing effects on key metabolic pathways that fuel cancer (eg. inhibition of mTOR. MTOR regulates mRNA translation initiation). 


Areas of focus: TRANSMIT

1. Cancer bioenergetics of different tumours. 

I have MR Spectroscopy, for example, and we can identify different metabolic signatures pertaining to different types of brain tumour fairly accurately from this. There may be some problems looking at areas where there is brain damage however, showing false positive results as you may see high signalling activity. It can sometimes be difficult to differentiate between malignant activity and areas of brain damage. 

2. How metabolic factors influence how cancer cells adapt to survive and proliferate could identify mitochondrial metabolic biomarkers for characterising the transformation from benign to cancer cells. 


What TRANSMIT is working on more specifically:

-Metabolic reprogramming of cancer cells- ie coordination of glutaminolysis and glycolysis. 

- Work with cancer cell models, metabolic intervention strategies.

- Improve our understanding of cancer pathology. 

- Understanding the role of fumarate hydratase in tumorigenesis.

- The mitochondrial complex 1 driven regulation of the hypoxic response in cancer cells. 

- Identifying coenzymes in cancer cells. 

26 comments:

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  2. Il ruolo del Sodio Nel cancro
    Per affamare Le cellule Tumorali, non è necessario ridurre il consumo di proteine e glucidi. Per affamare il tumore, basta ridurre il consumo di sodio (NaCl), dalla dieta. Devi sapere che la glutammina ed il glucosio, entrano nella cellula tumorale, accoppiati al sodio; se i livelli di sodio sono bassi, il glucosio e gli aminoacidi non riescono ad essere assorbiti dalla cellula tumorale. Le cellule Tumorali sono avide di Glucosio, glutammina e Sodio; Se il sodio è poco, glucosio e glutammina rallentano l'assorbimento.
    La Dieta Gerson per esempio è una dieta povera di sodio e ricco di magnesio e potassio. Attenzione! un po di sodio nella dieta ci vuole....

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    i am ERIC BRUNT by name. Greetings to every one that is reading this testimony. I have been rejected by my wife after three(3) years of marriage just because another Man had a spell on her and she left me and the kid to suffer. one day when i was reading through the web, i saw a post on how this spell caster on this address AKHERETEMPLE@gmail.com have help a woman to get back her husband and i gave him a reply to his address and he told me that a man had a spell on my wife and he told me that he will help me and after 3 days that i will have my wife back. i believed him and today i am glad to let you all know that this spell caster have the power to bring lovers back. because i am now happy with my wife. Thanks for helping me Dr Akhere contact him on email: AKHERETEMPLE@gmail.com
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    ReplyDelete
  20. Call Dr. Jakiki for urgent and fast love spell +1 (304) 441-7224 or email him Spellcasthome@gmail.com

     I lost my husband to another woman,after 4 years of marriage . We had a lovely marriage but he started a relationship with a co worker who chased after him . He is living away near his work and he refused to talk to me or to come home . I was so devastated and found it hard to cope. I became very worried and needed help. As I was browsing through the internet one day, I came across a comment by Amber that suggested that Dr Jakiki helped her solve her marital problems, restore broken relationships and so on. So, I felt I should give him a try. I contacted him and he did a spell for me. 2 days later, my husband came to me and apologized for the wrongs he did and promise never to do it again. Ever since then, everything has returned back to normal. I and my family are living together happily again.. All thanks to Dr Jakiki. If you need a spell caster that can cast a spell that truly works, I suggest you contact him. He will not disappoint you. I give you 100% guarantee that he will help you. His website: http://Spellcasthome.website2.me

    His email Spellcasthome@gmail.com 

    Call him +1 (304) 441-7224

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  21. What a wonderful and a straight forward spell caster that has brought back joy and happiness into my life! Am giving this testimony because am so happy, I want to thank Dr. Osasu for the great thing He has done in my life , He brought happiness back to my life, I never believed in spell casters until my life fell apart when my lover of 6 years decided to call it quit almost when we wanted to get married. I was so emotional breakdown to the extent i could not do anything reasonable again, after 2months in pain before an old friend of mine introduced me to a spell caster on line called Dr Osasu, this was after I have been scammed by various fake spell casters. I was introduced me to Dr Osasu a true Spell Caster. In less than 24 hours i saw wonders, my lover came back to me and my life got back just like a completed puzzle, and after 1month later we got married and it was just like a dream to me because i thought i had lost him forever. Thank you Dr. Osasu for helping me but most of all, Your Honesty and Fast Accurate Results. email: Drosasu25@gmail.com WhatsApp Number: +2347064365391

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  22. WHAT A GREAT MIRACLE THAT I HAVE EVER SEE IN MY LIFE. My names are Clara David I’m a citizen of USA, My younger sister was sicking of breast cancer and her name is Sandra David I and my family have taking her to all kind of hospital in USA still yet no good result. I decided to search for cancer cure so that was how I found a lady called Peter Lizzy. She was testifying  to the world about the goodness of a herbal man who has the roots and herbs to cure all kinds of disease and the herbal man's email was there. So I decided to contact the herbal man @herbalist_sakura for my younger sister's help to cure her breast cancer. I contacted him and told him my problem he told me that I should not worry that my sister cancer will be cure, he told me that there is a medicine that he is going to give me that I will cook it and give it to my sister to drink for one week, so I ask how can I receive the cure that I am in USA, he told me That I will pay for the delivery service. The courier service can transport it to me so he told me the amount I will pay, so my dad paid for the delivery fee. two days later I receive the cure from the courier service so I used it as the herbal man instructed me to, before the week complete my sister cancer was healed and it was like a dream to me not knowing that it was physical I and my family were very happy about the miracle of Doctor so my dad wanted to pay him 5 million us dollars the herbal man did not accept the offer from my dad, but I don't know why he didn't accept the offer, he only say that I should tell the world about him and his miracle he perform so am now here to tell the world about him if you or your relative is having any kind of disease that you can't get from the hospital please contact dr.sakuraspellalter@gmail.com or whats app him +2348110114739  you can follow him up on Instagram @herbalist_sakura for the cure, he will help you out with the problem. And if you need more information about the doctor you can mail me  or whatsApp  davidclara223@gmail.com +1(440)359-4106  

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  23. My life is back!!! After 1 years of Broken marriage, my husband left me with two kids . I felt like my life was about to end I almost committed suicide, I was emotionally down for a very long time. Thanks to a spell caster called Dr Mark, which I met online. On one faithful day, as I was browsing through the internet,I came across a lot of testimonies about this particular spell caster. Some people testified that he brought their Ex lover back, some testified that he restores womb,cure cancer,and other sickness, some testified that he can cast a spell to stop divorce and so on. I also came across one particular testimony,it was about a woman called Alandre,she testified about how he brought back her Ex lover in less than 2 days, and at the end of her testimony she dropped Dr Mark e-mail address. blessedlovetemple@gmail.com After reading all these,I decided to give it a try. I contacted him via email and explained my problem to him. In just 48 hours, my husband came back to me. We solved our issues, and we are even happier than before. Dr Mark is really a gifted man and I will not stop publishing him because he is a wonderful man... If you have a problem and you are looking for a real and genuine spell caster to solve all your problems for you. blessedlovetemple@gmail.com anytime, he might be the answer to your problems.

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  24. I was diagnosed as HEPATITIS B carrier in 2013 with fibrosis of the
    liver already present. I started on antiviral medications which
    reduced the viral load initially. After a couple of years the virus
    became resistant. I started on HEPATITIS B Herbal treatment from
    ULTIMATE LIFE CLINIC (www.ultimatelifeclinic.com) in March, 2020. Their
    treatment totally reversed the virus. I did another blood test after
    the 6 months long treatment and tested negative to the virus. Amazing
    treatment! This treatment is a breakthrough for all HBV carriers.

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  25. The worst time has passed”However, it is true that there are more improvements than before...because of the rising numbers of people living with HIV in the state of Nevada. How could they stigmatize all of them? Therefore everything becomes a little easier and we start to share everything... We also started to invite and visit each other in a community. You know, it is six years since I started taking antiretroviral drugs...Yet whatever problems I face, the worst time has passedWhen I was evicted from the family home by my mother, my father rented a small room for me. But my mother and brothers believed that having HIV was my own fault – and that I deserved to be punished...I also considered myself unworthy and without hope... But I have a child and eventually I convinced myself to live for my child’s sake.
    My mother knew nothing [about HIV]. She didn’t understand anything. Do you know why? She didn’t have [the chance] to go out of the house and communicate with society. However, my father does interact with the community. I know his friends are mature and dignified africa america. So he has a better understanding than her.My father came call me on a sadfull day sitting on my couch about a friend of his from africa who introduce him to Dr Itua herbal  cure in africa in which he advise we should purchase his herbal medicine to cure my hiv so we did and Dr Itua prescribed I should drink the herbal medicine for two weeks to cure although we were so curious about the whole thing ,I finished the herbal medicine like he advised then he talked to me to visit my nearest clinic for check up I did and now I'm totally cured from Hiv my father was my rock and I and my family are now happy together also Dr Itua has be helpful in my community ever since he cure my Hiv so why I'm leaving  my story on here today is to reach out someone out here to hope on God and never give up no matter the situation you that you are facing especially through this pandemic seasons which has really taught us all on how we should be helpful to each other and cherish one another.Dr Itua cures the following diseases.....  Herpes,Liver cancer,Throat cancerLeukemia.,Alzheimer's disease,Chronic Diarrhea,Copd,Parkinson,Als,Adrenocortical carcinoma  Infectious mononucleosis.
    Intestinal cancer,Uterine cancer,Fibroid,Bladder cancer,Hiv,Esophageal cancer,Gallbladder cancer,Kidney cancer,Hpv,Lung cancer,Melanoma,Mesothelioma,Multiple myeloma,Oral cancer,Sinus cancer,Hepatitis A,B/C,Skin cancer,Soft tissue sarcoma,Spinal cancer,Stomach cancer,Vaginal cancer,Vulvar cancer,
    Testicular cancer,Thyroid Cancer.You can contact Dr Itua Herbal Center on E-Mail: drituaherbalcenter@gmail.com  Or Whats-App Chat : +2348149277967

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