Cancer Vaccines | A survivors story|From Cancer Good Things Grow Grace Gawler

I encored a recent interview with Jeffery Deslandes on my Voice America Internet radio show today for the Christmas period for a special reason. Because his story is both true and inspirational.

I encored a recent interview with Jeffery Deslandes on my Voice America Internet radio show today for the Christmas period for a special reason. Because his story is both true and inspirational. As Jeffrey quotes in his recently released ;  book; “From Cancer Good Things Grow”;  there are about 4,000 new cases of NHL each year in Australia. 1600 Australian die from NHL each year. If this were our road toll and there was an effective way of preventing deaths of even half of that number – there would be campaigns and lots of public and political interest. Why is there such little  interest in cancer immunotherapies? Jeffrey Deslandes is just one of many who have had success with vaccine treatments.

The questions begs – Have we become so conditioned to believing that cancer is a one-way ticket and there’s nothing we can do apart from try alternative medicine and throw out the “conventional medicine” baby with the bathwater?  Have we been convinced that conventional cancer medicine doesn’t work and that all big Jeffrey Deslandes Book 001pharma wants you to do is stay sick to garnish the pockets of doctors?  Have we bought into the rumour that the war on cancer is lost?  These are common statements from the Google cancer entrepreneurs whose aim is to convince patients to follow them, buy their “one size fits all” cancer products and……… take no responsibility for patient outcomes.

I know of far too many  patients who are not here to be with their families this Christmas because they used “faceless” advice from books, CDs or the internet – leaving aside treatable and potentially curable treatments for their cancer until it became obvious that their attempts to replicate the “cures” they have read about; ultimately failed them. This year I have experienced a new phenomenon, receiving many emails from parents who have taken the natural cancer “healing” path with their children using bizarre nutritional regimens, GcMAF, Budwig and Gerson Diets to name a few – most read about these treatments on blogs. Some of these children have been 3 and 5 years of age.  I try my best to influence them towards excellent sources of conventional medicine – but after a few emails – I never hear from them again. This is truly exasperating!!

Genuine, well documented  stories of cancer treatment successes are much needed. Such is the story of how Melbournian Jeffery Deslandes recovered from Stage 4 recurrent lymphoma that had grown resistant to conventional treatment found his remission – now eight and a half years clear. Jeffery did not seek Alternative medicine treatments when his lymphoma recurred again and again; rather he looked outside the conventional box to see what else science-based medicine could offer.

By purchasing Jeffrey Deslandes book (soft Cover /eBook) – you can help to promote the immune therapy he had right here in Australia. All proceeds go toward making this treatment more available for those in our region. PLEASE spread the good news. Vaccine therapies as immunotherapies go wider than just lymphoma. Successes are appearing from many cancer types including melanoma, prostate cancer and many more. If these therapies can be investigated alongside immune cycle research; we may indeed have a two incredibly power non invasive cancer treatment allies. Scroll to end of blog to see the effect of melanoma vaccine.**

Excerpts from Jeffrey Deslandes book “From Cancer Good things Grow”.


Chapter 7 -The cancer Returns Again and Again

Non-Hodgkin’s lymphoma is a bit like buffalo grass; it is hard to get out all of the roots and it tends to grow back. I had been informed that my cancer was incurable. It was a real shock at the time.
Non-Hodgkin’s lymphoma (NHL) is Australia’s fifth most common cancer, yet has a very low profile, compared to more publicised cancers such as breast, ovarian, bowel, melanoma and leukaemia. There are about 4,000 new cases of NHL each year in Australia, with about 1,600 deaths each year. That’s about the same as the National Road Toll in this country. Each year we spend billions trying to stop idiots killing each other on the road, yet comparatively little on a disease which is poorly understood. While Australia’s economy is soon to be taxed with the introduction of a Carbon Tax to combat Climate Change. Funny that, I have never known anyone who has died from Climate Change, but I have known scores and scores of people who have succumbed to cancer. We need Governments to spend serious money on cancer research.

After my cancer had returned for the fourth time in 2006, the next mainstream cancer treatment outlined by my specialist, was an autologous stem cell transplant. An autologous stem cell transplant, refers to your own body’s stem cells being first harvested, you are then given high-dose chemotherapy to hopefully kill all cancer in your body, and your stem cells

Jeffrey Deslandes
Jeffrey Deslandes

are then re-infused to build up your white cells, which have been decimated by the chemotherapy. The other option was an allogeneic stem cell transplant; the same procedure but the stem cells are used from a matched donor who is obviously free from cancer. However, for this we would need to find a matched donor, since my brother Ron was not a match, and other brother David was no longer with us. I decided not to take the recommendation of my highly trained lymphoma specialist. I decided that I would need to take charge of my treatment, and find something with a different mode of attack. If something is not working, you don’t keep hitting it with the same old stick! Read on,,,,,,,,

Chapter 8 – Vaccine Therapy–The New Beginning

Through my association with Lymphoma Australia, a fine not-for-profit organisation dedicated to raising awareness and supporting lymphoma patients, I became aware of work being done on vaccines for cancer treatment. This work was still experimental or being proven in clinical trials, but it was not quackery, it was being carried out by highly qualified haematologists and scientists.

My diseased lymph node, and my immature dendritic cells, were processed in the laboratory to manufacture a dendritic cell idiotype vaccine to fight the cancer. It is termed idiotype, because the vaccine is grown from my own cancer cells, and is thus specifically tailored to the idiosyncrasies of my cancer. It is worth noting that there are over 30 sub-types of lymphoma alone, and it is my understanding that each and every lymphoma is going to be somewhat different in its individual characteristics. By using my own lymphoma, we got a perfect match, the exact antibody to my cancer. The laboratory grew the vaccine formulation to make 33 doses of vaccine, which were stored at minus 196 °C in liquid nitrogen, and could be kept for perpetuity. Each dose of vaccine is about 1 ml, about a fifth of a teaspoon, but it contains about five million cells. Yes, that’s five million cells, each with a message for my immune system. The message was “this is what the cancer looks like, now do your job like you are supposed to, and go seek and destroy”.  Excerpt: “From Cancer Good Things Grow”

Help save a life ……… Readers of this blog – please help us to help others through cancer education. By passing on this blog or an episode from Voice America – you could also help cancer patients to re-frame their cancer experience and learn about the nature of cancer and how to outsmart it with science-based medicine.

May your Christmas season be filled with joy, love, passion and compassion….

Until next time….


**Warning:  Below – graphic image melanoma – positive results from repeated vaccine cancer treatments.

Conclusions: Prolonged, repetitive VMCL vaccination immunotherapy appears to be a clinically effective means
of generating relatively high CR rates, useful clinical responses and long-term survivals, with little toxicity, but
remains notably under-explored. Successive immunomodulation might explain the results. Closer analysis of
repetitive dosing is required.

Melanoma vaccines
Successful application of repeated dosing with Melanoma vaccines. Research- Brendon Coventry

Cancer Doesn’t Stop for Christmas | Dealing with the Challenges-Grace Gawler Voice America

Navigating the Cancer Maze represents the culmination of my 40 years experience working at the coalface of cancer in what I call cancer supportive care medicine. As a young girl of about 8 years of age – I had two ambitions in life; to research cancer or become a veterinary surgeon. The universe works in mysterious ways. In 1976 I married a veterinarian who had cancer.

Click headphones to listen to today’s show at Voice America

Today’s Navigating the Cancer Maze, covers several areas important to Cancer patients.

In addition to this blog – gracegawlermedia – on Sunday 21st December 2014 – I will be launching a new blockbuster or should I say myth-buster blog – Grace Gawler Blog: The Thinking Person’s Guide to the Truth behind Common Cancer Mythology.

Navigating the Cancer Maze represents the culmination of my 40 years experience working at the coalface of cancer in what I call cancer supportive care medicine. As a young girl of about 8 years of age – I had two ambitions in life; to research cancer or become a veterinary surgeon. The universe works in mysterious ways. In 1976 I married a veterinarian who had cancer.

It happened just a few days before Christmas in 1974 – 40 years ago when I had just turned 21. Suddenly I became a carer of a cancer patient who was my boyfriend and employer.

My wedding day 28 Feb 1976 - 21 years and full-time carer
My wedding day 28 Feb 1976 – 21 years and full-time carer

 Like many today I had no experience in how to cope personally or how to help the patient who was my charge. I had to improvise and learn along the way. Added to this, my boyfriend, who later became my husband when he was given a prognosis 6 weeks to live; was an amputee. He had lost his leg to bone cancer just after Christmas, January 1975. He survived, we had 4 children and now 4 grandchildren. I learned a lot during that “hands-on period” that added to later qualifications. My story of those times is recorded in my Memoirs: Grace Grit and Gratitude. (2008 – eBook available)

See You tube: Grace Grit and Gratitude  Also visit on the menu of this blog –  “Ian Gawler Cancer?”

Moving forward to 2012 I realised that consulting with patients and public speaking was not enough. With cancer incidence rising, what I had learned needed a Global voice; an opportunity to take what I had learned so far and add medical expertise in current cancer treatments and research combined with patients’ experiences.

Available eBook - buy soft cover Australia only
Available eBook – buy soft cover Australia only

Patient’s need reliable and genuine information when they are in the fight for their lives! 2014 marks 2 years on air with Voice America’s Health and Wellness Channel hosting ‘Navigating the Cancer Maze’. We want as many people as possible to know about Navigating the Cancer Maze internet radio because my Charity The Grace Gawler Institute sponsors this show to provide education and information free to all in need. Please visit the Website for our Christmas Fundraiser to support the show for 2015: “Move the World with Grace”

On this week’s pre-Christmas show I discuss key issues for cancer patients that have been highlighted by our guests on Navigating the Cancer Maze throughout 2014; a year of challenges and excitements in the Global Cancer Community. We will take a look at the impact of some of cancer’s entrepreneurs Including Wellness Warrior-Jess Ainscough, who has influenced many patients to follow the natural path to cancer healing, albeit encouraged by the Ian Gawler recovery story, which as you know, was highly likely to have been a misdiagnosis.

Unfortunately, but as expected; Jess’s Epithelioid sarcoma, a cancer that moves slowly has now progressed to a serious degree. Her mum recently died from breast cancer doing the same regimen. Entrepreneurial patients like Jess Ainscough have a huge influence on cancer patient’s treatment decisions. I truly despair at these stories. I hear from cancer patients like Jess daily and see them in my practice with the most horrendous fungating cancers that one would would expect to see in a third world country. I am passionate to educate cancer patients about the dangers of taking the 100% natural therapies approach. As a trained naturopath and herbalist-I am horrified by what I see hear and read about natural cancer cures!
More on this visit-Science -based Medicine Blog and See  Jessica Ainscough Wellness Warrior

Finally….Cancer Doesn’t Stop at Christmas:While for some this is a happy time of year – for others Christmas and New Year celebrations can be very a difficult & emotional time for those currently dealing with life challenging illness, including patients’ families. Also challenging is the person who may be missing from this year’s Christmas table. Please see helpful resources below – also listen to today’s show for helpful tips
Many of my Guests on Navigating the Cancer Maze have authored some fine books. I have listed them below. These are books of substance that contain valid and useful information for patients and families. Recommended for Christmas gifts or personal reading

Resources/Books mentioned on today’s show from my 2014 Guests:

  1. From Cancer Good Things Grow Jeffrey Deslandes – 8.5 year survivor of stage 4 lymphoma after failed treatments – 4 recurrences. Success with Dendritic cell vaccines. Pub  Balboa Pressall proceeds go to R& D Of DC Vaccines.
  2. “Three Months: A Caregiving Journey from Heartbreak to Healing” by Dietrich Stroeh Buy at Amazon
  3.  Recent Release-” Survivorship: Living Well During and After Cancer” by Dr Barrie Cassileth –
    Buy at:
  4. “Bad to the Bone: the True Story of David Tuccaro, Jr” – by David Tuccaro, Jr successful leukemia treatment- Buy at Amazon
  5. “Lead With Your Heart: Creating a Life of Love, Compassion, and Purpose”  by Regina Cates Buy at Amazon
  6. “The Man who Saved a Million Lives” – by Prof Ian Frazer Buy at Amazon
  7. Spontaneous Remission: An Annotated Bibliography by Caryle Hirshberg and Brendon O’Regan – Access this via IONS- Free chapter downloads:


Debbie Franke Ogg had a Hollywood Movie made about her life and recovery from Stage 4 Lymphoma. It starred Sam Neil and Anne Archer. First titled “A Leap of Faith” – the movie was later titled a “Question of Faith”. Debby is perhaps one of the few of millions who had a spontaneous remission from her cancer without medical treatment. The movie can be found online by typing the title into Google. Now a therapist in NY USA – Watch Movie online   Contact Debby.

Cancer Doesn’t Stop at Christmas: Help for those who may have lost a loved one this year. Resources provided by Beth O’Brien: a guest on this year’s Navigating the Cancer Maze.
BOOK recommended by Beth:
Dying to be Free: A healing guide for families after a suicide (Beverly Cobain, Jean Larch) buy at Amazon
The Grief Recovery Handbook: The action program for moving beyond Death, Divorce and other losses by John W James and Russell Friedman Buy at Amazon

Listen to today’s show at

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Until next time – Compliments of the Christmas Season


From Cancer Good Things Grow – A Survivor’s Story|Grace Gawler Interviews Jeffrey Deslandes

Jeffrey Deslandes thought he had it all. The father of five children, he had his whole life ahead of him. But on one fateful day in 1999, he believed it was all over when he was diagnosed with an aggressive form of cancer. He was wrong. His life had just begun!

from cancer good things growA true story of survival: Share the good news. Listen to Navigating the Cancer Maze: From Cancer Good Things Grow.  If you know someone with lymphoma, leukaemia, melanoma or other cancers – you need to tell them about Jeffrey Deslandes and how he survived and thrive thanks to cancer vaccines. They need to read his story.

Jeffrey Deslandes thought he had it all. The father of five children, he had his whole life ahead of him. But on one fateful day in 1999, he believed it was all over when he was diagnosed with an aggressive form of cancer. He was wrong. His life had just begun!

His diagnosis, B cell non-Hodgkin’s lymphoma, follicular mixed small and large cell, Stage IV, with bcl-2 gene translocation, with spleen and bone marrow involvement. His prognosis; poor.

His is an inspiring, positive, and true story about surviving cancer—and the things it teaches you. You grow as a person. You learn what is really important in life. You discover who your true friends are. Listen to my interview with Jeffrey on Voice America’s Health & Wellness Channel – Navigating the Cancer Maze: From Cancer Good Things Grow.  (Note: The show is sponsored by the Grace Gawler Institute. Free to listen – live stream on demand – select link above or download and listen another time – share with friends and fellow patients. Live broadcast 12 noon Friday – USA time(PST) – Australia – 6 am Qld time.

After traditional treatments, such as chemotherapy, failed to control his cancer, Jeffrey started looking for emerging therapies. When he learned of an experimental treatment involving a personalised vaccine protocol, he pursued it. It is now feasible to have something good—a personalised cancer vaccine—created from something bad—your cancer. This one-of-a-kind vaccine reeducated his immune system so that it could identify and destroy his cancer.

Jeffrey’s story is not a gloom-and-doom tale of yet another poor soul enduring cancer treatment. Instead, he shares his story in the hope of reaching and inspiring other cancer patients who may have given up. Some of the stories in this book come from his deep spiritual core, but he is not a “religious” man. He doesn’t require you to believe these stories, only to know that everything detailed in this book is true.

See Press pass info – share this link to others.

ABOUT Jeffrey Deslandes: Jeffrey is a native of Melbourne, Australia. He has a Masters in Engineering Science, and is a Doctor of Philosophy, attained at the University of Melbourne. He has been married twice and has five children.  His is an inspiring, positive, and true story about surviving cancer—and the things it teaches you. You grow as a person. You learn what is really important in life. Compelled to write about his experience. “From Cancer Good Things Grow” was published recently. Available as ebook and soft cover.(Balboa Press) BUY online at: Balboa Press:

All proceeds from the sale of this book go directly to cancer vaccine research in Brisbane where Jeffrey had his treatment. He wants more people to know about his doctor and the the hope that vaccines bring for recovery. For more information about Jeffrey’s treatment – please contact me via the contact page on this BLOG or via

Note: Dendritic cell vaccines are highly technical and need rigorous quality control and expertise. Ask me for further information on how to access this treatment.

VOICE AMERICA LINK to listen to audio:

Until next time…… Grace

Options, Choices and Treatments for Cancer Recovery| Navigating the Cancer Maze

New cancer treatments are always controversial; BUT – this method is not a treatment. It’s a smart approach. A Smart approach that utilizes all that we know so far about cancer. It works because ultimately; our innate immune system knows what to do.

Options, Choices and Treatments for Cancer Recovery: De mystifying the oscillating the immune cycle.

When my ex husband and I had the idea for starting support groups for cancer patients in the early 1980’s. cancer organizations, patients and doctors were initially not supportive. In fact they were skeptical. They could not see any possible therapeutic benefit could come from people attending a support group.  How wrong they were! Move forward Body rhythms diagram40 years! Yes this December marks my beginning working with cancer patients 40 years ago in a time when there was no support in the health system and no support groups. Now, the benefit of patients attending structured supports and the well being benefit is indisputable.

There are still many new areas to explore, which leads me to discussing the immune cycle. It would seem that during 2014 on Navigating the Cancer Maze – we uncovered and delivered some significant “missing” pieces of the cancer treatment puzzle. It is my hope that as 2014 comes to an end – that 2015 will truly usher in a new paradigm in cancer treatments. The foundation has been laid, extensive research already done, the concept has been introduced worldwide – the  immune cycle measurement is here – NOW!
Now it is up to cancer patients to prove Martin Ashdown and Brendon Coventry right….or wrong. I liked it when Martin Ashdown said – “We believe this is so, a breakthrough – but we are open to being proven wrong!” As in the early days of my first charitable  foundation – it was people power – patient power that made a difference to the success of the Cancer Support Group Movement. Once told there would likely be a measured benefit from attending a support group – the press broadcast the news and the patients came on board en masse!

New cancer treatments are always controversial; BUT – this method is not a treatment. It’s a smart approach. A Smart approach that utilizes all that we know so far about cancer. It works because ultimately; our innate immune system knows what to do. It is just in temporary overwhelm. So doesn’t it make perfect sense that to find the best time to work in synch within the cycle of each person’s immune system to add the best chemotherapy or monoclonal antibody or other targeted treatment. Isn’t this the personalized approach we have been searching for? We all thought it would come in a pill – not an approach and that’s a paradigm shift that some in the world of science and medicine are struggling with.

measuring immune cycleKnowing how one’s immune cycle oscillates holds a clue, “the missing link” that can direct doctors to seek the best time to treat patients in their personal window of opportunity. Then within the parameters of what we know they will have the best chance of a good response or complete response to treatment. (CR)

When cancer cells challenge us – they are also smart. They are a part of us created by our internal systems. You could define cancer as an internal systems error!  These cancer cells cleverly recruit our intelligent mechanisms using them for their own growth and survival. It seems a bit crazy that something that wants to survive – kills its host. But – that’s life! To listen to the latest Voice America related to this blog visit:

So – I believe as do Ashdown and Coventry – that if there is enough of the immune response left in a patient – that the cycle can still be measured and timed so administer the right treatment at the right time. It is simple enough – the only real cost being a series of blood tests. Then finding a doctor who will look at the science and research and say yes – they administer treatment during the 12 hour window of opportunity. The Grace Gawler Institute is keen to let you know and experience the immune cycle for yourself. Please Read more below or join the immune cycle registry at: also see our Next “Survivor Academy” Course!

Martin Ashdown and Brendon Coventry have built upon earlier excellent work in the study of chronobiology: Below are references given on Navigating the Cancer Maze today: I have provided abstract content as well as links.

Until next time……Grace

  • Annu Rev Pharmacol Toxicol. 2010;50:377-421. doi: 10.1146/annurev.pharmtox.48.113006.094626.
    Circadian timing in cancer treatments.
    Lévi F1, Okyar A, Dulong S, Innominato PF, Clairambault J.
    Author information
    The circadian timing system is composed of molecular clocks, which drive 24-h changes in xenobiotic metabolism and detoxification, cell cycle events, DNA repair, apoptosis, and angiogenesis. The cellular circadian clocks are coordinated by endogenous physiological rhythms, so that they tick in synchrony in the host tissues that can be damaged by anticancer agents. As a result, circadian timing can modify 2- to 10-fold the tolerability of anticancer medications in experimental models and in cancer patients. Improved efficacy is also seen when drugs are given near their respective times of best tolerability, due to (a) inherently poor circadian entrainment of tumors and (b) persistent circadian entrainment of healthy tissues. Conversely, host clocks are disrupted whenever anticancer drugs are administered at their most toxic time. On the other hand, circadian disruption accelerates experimental and clinical cancer processes. Gender, circadian physiology, clock genes, and cell cycle critically affect outcome on cancer chronotherapeutics. Mathematical and systems biology approaches currently develop and integrate theoretical, experimental, and technological tools in order to further optimize and personalize the circadian administration of cancer treatments.
    [PubMed – indexed for MEDLINE]

Ann Pharm Fr. 2008 Jun;66(3):175-84. doi: 10.1016/j.pharma.2008.05.003.
[The circadian-timing system: a determinant of drug activity and a target of anticancer treatments].
[Article in French]
Lévi F.
Author information
Cellular proliferation and drug detoxification are controlled over the 24h by the circadian-timing system, whose disruption can favor malignant processes. Thus, prolonged shift work appears to increase the risk of breast, colon or prostate cancer. Alterations in circadian physiology and/or molecular-clock genes accelerate cancer progression in experimental models and in cancer patients. In addition, anticancer treatments can also dampen or reinforce the circadian-timing system, as a function of dose and time of administration. The adjustment of anticancer-drug delivery to the circadian-timing system (chronotherapeutics) has allowed to reduce five-fold the incidence of severe adverse events as compared to constant rate infusion or wrongly-timed chronomodulated delivery in cancer patients. In experimental models, the best antitumor efficacy is usually obtained following treatment delivery near the least toxic time, a statement that also seems to apply to patients. Dedicated technologies include programmable in time pumps and rhythm monitors and are required for chronotherapeutics. Recent results have revealed that the optimal chronotherapeutic schedule could differ as a function of gender and circadian physiology. In conclusion, the circadian-timing system was shown to negatively control malignant proliferation via partly identified molecular mechanisms. The components of the circadian-timing system thus constitute new potential therapeutic targets in oncology. Mathematical models help toward a better understanding of the role of variability for the determination of the optimal chronotherapeutic schedule and constitute useful tools for the personalization of cancer chronotherapeutics.

Handb Exp Pharmacol. 2013;(217):261-88. doi: 10.1007/978-3-642-25950-0_11.
Cancer chronotherapeutics: experimental, theoretical, and clinical aspects.
Ortiz-Tudela E1, Mteyrek A, Ballesta A, Innominato PF, Lévi F.
Author information
The circadian timing system controls cell cycle, apoptosis, drug bioactivation, and transport and detoxification mechanisms in healthy tissues. As a consequence, the tolerability of cancer chemotherapy varies up to several folds as a function of circadian timing of drug administration in experimental models. Best antitumor efficacy of single-agent or combination chemotherapy usually corresponds to the delivery of anticancer drugs near their respective times of best tolerability. Mathematical models reveal that such coincidence between chronotolerance and chronoefficacy is best explained by differences in the circadian and cell cycle dynamics of host and cancer cells, especially with regard circadian entrainment and cell cycle variability. In the clinic, a large improvement in tolerability was shown in international randomized trials where cancer patients received the same sinusoidal chronotherapy schedule over 24h as compared to constant-rate infusion or wrongly timed chronotherapy. However, sex, genetic background, and lifestyle were found to influence optimal chronotherapy scheduling. These findings support systems biology approaches to cancer chronotherapeutics. They involve the systematic experimental mapping and modeling of chronopharmacology pathways in synchronized cell cultures and their adjustment to mouse models of both sexes and distinct genetic background, as recently shown for irinotecan. Model-based personalized circadian drug delivery aims at jointly improving tolerability and efficacy of anticancer drugs based on the circadian timing system of individual patients, using dedicated circadian biomarker and drug delivery technologies.

Chronobiol Int. 2002 Jan;19(1):1-19.
From circadian rhythms to cancer chronotherapeutics.
Lévi F.
Author information
Mammalian circadian rhythms result from a complex organization involving molecular clocks within nearly all “normal” cells and a dedicated neuroanatomical system, which coordinates the so-called “peripheral oscillators.” The core of the central clock system is constituted by the suprachiasmatic nuclei that are located on the floor of the hypothalamus. Our understanding of the mechanisms of circadian rhythm generation and coordination processes has grown rapidly over the past few years. In parallel, we have learnt how to use the predictable changes in cellular metabolism or proliferation along the 24h time scale in order to improve treatment outcome for a variety of diseases, including cancer. The chronotherapeutics of malignant diseases has emerged as a result of a consistent development ranging from experimental, clinical, and technological prerequisites to multicenter clinical trials of chronomodulated delivery schedules. Indeed large dosing-time dependencies characterize the tolerability of anticancer agents in mice or rats, a better efficacy usually results from treatment administration near the least toxic circadian time in rodent tumor models. Programmable in time multichannel pumps have allowed to test the chronotherapy concepts in cancer patients and to implement chronomodulated delivery schedules in current practice. Clinical phase I and II trials have established the feasibility, the safety, and the activity of the chronotherapy schedules, so that this treatment method has undergone further evaluation in international multicenter phase III trials. Overall, more than 2,000 patients with metastatic disease have been registered in chronotherapy trials. Improved tolerability and/or better antitumor activity have been demonstrated in randomized multicenter studies involving large patient cohorts. The relation between circadian rhythmicity and quality of life and even survival has also been a puzzling finding over the recent years. An essential step toward further developments of circadian-timed therapy has been the recent constitution of a Chronotherapy cooperative group within the European Organization for Research and Treatment of Cancer. This group now involves over 40 institutions in 12 countries. It is conducting currently six trials and preparing four new studies. The 19 contributions in this special issue reflect the current status and perspectives of the several components of cancer chronotherapeutics.
[PubMed – indexed for MEDLINE]
Cancer Causes Control. 2006 May;17(4):611-21.
Chronotherapeutics: the relevance of timing in cancer therapy.
Lévi F.
Author information
Cell physiology is regulated along the 24-h time scale by a circadian timing system composed of molecular clocks within each cell and a central coordination system in the brain. The mammalian molecular clock is made of interconnected molecular loops involving at least 12 circadian genes. The cellular clocks are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker which also helps the organism adjust to environmental cycles. The rest-activity rhythm is a reliable marker of the circadian system function in both rodents and man. This circadian organization is responsible for predictable changes in the tolerability and efficacy of anticancer agents, and possibly also in tumor promotion or growth.
Expected least toxic times of chemotherapy were extrapolated from experimental models to human subjects with reference to the rest-activity cycle. The clinical relevance of the chronotherapy principle, i.e. treatment administration as a function of rhythms, has been demonstrated in randomized multicenter trials.
Chronotherapeutic schedules have been used to safely document the activity of the association of oxaliplatin, 5-FU and leucovorin against metastatic colorectal cancer and to set up a new medicosurgical management of this disease which achieved unprecedented long term survival.
The chronotherapy concept offers further promises for improving current cancer treatment options as well as for optimizing the development of new anticancer or supportive agents.
[PubMed – indexed for MEDLINE]

Mol Med. 2012 Dec 6;18:1249-60. doi: 10.2119/molmed.2012.00077.
Circadian rhythm disruption in cancer biology.
Savvidis C1, Koutsilieris M.
Author information
Circadian rhythms show universally a 24-h oscillation pattern in metabolic, physiological and behavioral functions of almost all species. This pattern is due to a fundamental adaptation to the rotation of Earth around its own axis. Molecular mechanisms of generation of circadian rhythms organize a biochemical network in suprachiasmatic nucleus and peripheral tissues, building cell autonomous clock pacemakers. Rhythmicity is observed in transcriptional expression of a wide range of clock-controlled genes that regulate a variety of normal cell functions, such as cell division and proliferation. Desynchrony of this rhythmicity seems to be implicated in several pathologic conditions, including tumorigenesis and progression of cancer. In 2007, the International Agency for Research on Cancer (IARC) categorized “shiftwork that involves circadian disruption [as] probably carcinogenic to humans” (Group 2A in the IARC classification system of carcinogenic potency of an agent) (Painting, Firefighting, and Shiftwork; IARC; 2007). This review discusses the potential relation between disruptions of normal circadian rhythms with genetic driving machinery of cancer. Elucidation of the role of clockwork disruption, such as exposure to light at night and sleep disruption, in cancer biology could be important in developing new targeted anticancer therapies, optimizing individualized chronotherapy and modifying lighting environment in workplaces or homes.
[PubMed – indexed for MEDLINE]
Free PMC Article

Chronobiol Int. 2012 Apr;29(3):227-51. doi: 10.3109/07420528.2012.658127.
Clock genes and clock-controlled genes in the regulation of metabolic rhythms.
Mazzoccoli G1, Pazienza V, Vinciguerra M.
Author information
Daily rotation of the Earth on its axis and yearly revolution around the Sun impose to living organisms adaptation to nyctohemeral and seasonal periodicity. Terrestrial life forms have developed endogenous molecular circadian clocks to synchronize their behavioral, biological, and metabolic rhythms to environmental cues, with the aim to perform at their best over a 24-h span. The coordinated circadian regulation of sleep/wake, rest/activity, fasting/feeding, and catabolic/anabolic cycles is crucial for optimal health. Circadian rhythms in gene expression synchronize biochemical processes and metabolic fluxes with the external environment, allowing the organism to function effectively in response to predictable physiological challenges. In mammals, this daily timekeeping is driven by the biological clocks of the circadian timing system, composed of master molecular oscillators within the suprachiasmatic nuclei of the hypothalamus, pacing self-sustained and cell-autonomous molecular oscillators in peripheral tissues through neural and humoral signals. Nutritional status is sensed by nuclear receptors and coreceptors, transcriptional regulatory proteins, and protein kinases, which synchronize metabolic gene expression and epigenetic modification, as well as energy production and expenditure, with behavioral and light-dark alternance. Physiological rhythmicity characterizes these biological processes and body functions, and multiple rhythms coexist presenting different phases, which may determine different ways of coordination among the circadian patterns, at both the cellular and whole-body levels. A complete loss of rhythmicity or a change of phase may alter the physiological array of rhythms, with the onset of chronodisruption or internal desynchronization, leading to metabolic derangement and disease, i.e., chronopathology.
[PubMed – indexed for MEDLINE]