Updated March 2016 – For more information on GcMAF, please join the GcMAF and GcMAF Cancer forums on Facebook – they are closed groups, so you have to wait for your membership to be confirmed. They contain up-to-date information on sources of GcMAF, and also feedback and contributions by people who are using GcMAF.
New developments on Breast Cancer and Cancer, culled from Google Alerts, for the week ending 18 April 2014.
Well, I was all geared-up for a glut of news developments because the American Association for Cancer Research recently held its annual conference, and was disappointed. Maybe the doctors are still partying away in San Diego!
For me, the top two eyecatchers this week is a study being done on spontaneous remissions – whether there is any genetic basis behind these miracle cures – and a blood test that has been developed that can predict recurrences. The final item is an editorial in Nature Journal about how we need a new approach to studying the genetics of cancer, it’s a long article about the Cancer Genome Atlas. What the article is saying is that the Cancer Genome Atlas has done a great job in amassing huge amounts of data, but simply cataloguing cancer mutations in the hope of finding a pattern isn’t delivering much-anticipated breakthroughs – we need to focus on the function of these genes as well.
Five people I’ve met who’ve had spontaneous remissions …
You’ve probably heard of, or even come across people who’ve experienced spontaneous remissions. If I hadn’t personally met five people to whom this had happened, I wouldn’t have believed it was possible.
Even more amazing, their remissions were achieved without conventional standard-of-care treatment.
One woman had Stage 4 Non-Hodgkins (with proof using blood tests, scans and biopsies). She underwent an intensive course of supplements, juicing, raw vegan diet and multiple sessions from a QiGong master (which at £500 a session was no joke), and was cured. This was over 2 years ago. Recent scans show she is still clear.
Another was a woman with inoperable breast cancer (as the tumour had grown into the sternum). – she was told by the hospital she could have palliative chemotherapy or go home and die. Again, she used diet, supplements and the same QiGong master and did intensive QiGong, acupuncture and positive visualisation. Result: the tumour regressed and became stable, and this was 20 years ago. – she is over 80 years old.
Or the woman I met who used IV C and diet and supplements for a Grade 2, 4cm breast tumour which has shrunk to the size of an apple pip and inactive – that was 6 years ago. And I know of two people who used GcMAF and got remissions from Stage 4 ovarian and prostate cancer.
I can’t help but be filled with envy at these individuals. But even if they had used standard-of-care treatments, it would still be a miracle if the cancer didn’t return. If only there was a way of creating vaccines from these lucky individuals!
[please see comment left by reader JT with information on a fantastic article in Cancer Immunity Journal on the discovery of Spontaneous Regression and Complete Resistance in Mice: http://archive.cancerimmunity.org/v3p14/031016.htm – thanks, JT!]
Remission (without constant surveillance) is a temporary state
What I’ve realised in this cancer journey is that while we’re all primed for the best outcome (i.e. a cure), the reality is all the medical profession can offer us is a remission (i.e. a period of time cancer-free before it returns). So, really all the treatments are doing is buying some time before it returns. Which is a con when you think of how awful the treatments are.
We’ve all had friends who put themselves through the most ghastly radiotherapy and chemo regimes for their primary breast tumour only for the cancer to return and metastasise several years later. Why?
You cannot take your eye off cancer – the imprecision of current tests
Tumour markers are not always a good indicator of what’s going on, and Pet-CTs can only detect tumours above a certain dimension. The problem is one of sensitivity, and vigilance. It seems to me that there seems to be a tacit agreement in the oncological trade that once you’ve been zapped (or in the words of a surgeon I know “disinfected”) with chemo, it’s a matter of watch-and-wait, or let’s play the statistics game. Unfortunately, by the time patients go to the doctor complaining of a back-ache that won’t go away, it’s too late – the cancer is back and galloping away.
And every cancer patient will testify to the anxiety that greets the end of treatments – now that they’re not doing anything that’s actively killing cancer cells, how can they be sure the cancer’s not going to return? And when the cancer does return, there’s a loss of faith in the whole process and the medical profession, and one’s body’s ability to heal.
What cancer patients need is a test that can accurately measure the degree of responsiveness to treatments, and in the months post-treatment, a test that will give them the peace-of-mind that the cancer is truly in remission, or to warn them if it’s about to gallop.
The need for tests that are sensitive enough to predict recurrences or progression
I used to think that the only way to test for response to treatments was to use Circulating Tumour Cell or Stem Cell counts in the blood. But this is not a test that is offered on the public health service, and most insurance companies won’t pay for this test (at least in the UK) because it has not been put on the list of approved tests by NICE (in the UK). There are a few labs for this test: RGCC Europe (Greece – OncoTrail and OncoTrace tests), MainTrac in Germany, and a few in the US. They are expensive, and if you need to repeat them regularly (like every 3 months), this soon adds up.
Also, using CTCs to measure progression is not always accurate. I’ve heard of people who had zero CTC counts who had recurrences months later. Back to the drawing board!
Just like there doesn’t seem to be a single magic bullet that can cure cancer, there doesn’t seem to be a single test that can keep an eye on cancer’s wily progression.
This preamble is a roundabout way of saying whoopee – there’s now a blood test that can predict recurrences and it doesn’t involve counting circulating tumour cells. You can read all about it in Item 2. It’s still not on commercial release yet, and I hope that it’s an affordable test so that women can have it as frequently as they need to.
[What about the OncoType DX? Well, it’s a step in the right direction, but doesn’t really count because it shows what is the likelihood of recurrence post-surgery (based on tumour pathology) if standard-of-care isn’t used. Also, what pisses me off is that it’s just a percentage predictor, and the lab is very mysterious about what genes are tested or not.]
We are being let down by the medical profession if there isn’t regular testing that can accurately predict recurrence or responsiveness to treatments. Without such a test, surviving cancer is like living in the shadow of a volcano that is going to explode … but we don’t know when.
1. Researching the genetics behind spontaneous remissions
- The history of cancer treatments is full of reports of patients with advanced cancer who staged miraculous recoveries.
- Now scientists are starting to use sophisticated DNA sequencing technology to determine if these “exceptional responders” carry gene variations that can lead to new treatment approaches, better targeted therapies or even the re- emergence of experimental drugs once deemed failures.
- The mystery surrounding Jan Crisitello, a 70-year-old grandmother of four, is a case in point. Five years ago, 29 patients with advanced melanoma enrolled in a trial of a drug under development by Pfizer. Only one, Crisitello, came away with her cancer in remission. Now, she is being studied to see how her unique genome may have interacted with the drug to spur her recovery.
- Now, the National Cancer Institute and academic medical centers including Memorial Sloan-Kettering Cancer Center in New York, the Dana-Farber Cancer Institute and Massachusetts General Hospital in Boston, and the Broad Institute in Cambridge, Mass., are collecting data to conduct a more complete survey of exceptional responders. The plan is to create a national database for researchers.
- So far, about 100 exceptional responders have been identified by researchers poring through about 10 years of clinical trials, said Barbara Conley, associate director of the NCI’s Cancer Diagnosis Program.
- The research also can help refine the advances already made in targeted cancer treatments and immunotherapies.
- Unlike traditional chemotherapy, which kills healthy cells along with malignant ones, targeted therapies are designed to home in on specific biological aspects of cancer cells that promote a tumor’s spread and growth. Still, most patients develop resistance and the disease returns.
- One patient’s dramatic results from a targeted therapy that doesn’t help others suggests another genetic feature may be involved. By identifying a mutation in an exceptional responder, researchers can then screen other patients to see if they have the same alteration, and give them the same drug.
2. Blood test accurately predicts recurrent breast cancers and also monitors response to treatment
- Johns Hopkins Kimmel Cancer Center investigators report they have designed a blood test that accurately detects the presence of advanced breast cancer and also holds promise for precisely monitoring response to cancer treatment.
- The cMethDNA assay is a blood-based test built on a panel of 10 breast cancer-specific genes.
- Blood collected from breast cancer patients is processed to isolate circulating tumor DNA, and the assay detects if any of the 10 genes are hypermethylated, a process by which the activity of some genes that keep the cancers in check are “silenced.”
- Detection of hypermethylation in any of these genes in blood indicates that the patient may have a disease recurrence.
- Currently, there is no useful laboratory test to monitor patients with early stage breast cancer who are doing well, but could have an asymptomatic recurrence.
- To design the test,researchers scanned the genomes of primary breast cancer patients, as well as DNA from the blood of metastatic cancer patients.
- They selected 10 genes specifically altered in breast cancers, including newly identified genetic markers AKR1B1, COL6A2, GPX7, HIST1H3C, HOX B4, RASGRF2, as well as TM6SF1, RASSF1, ARHGEF7, and TMEFF2, which Sukumar’s team had previously linked to primary breast cancer.
- The investigators also studied the assay’s potential to monitor response to chemotherapy.
- The test detected a significant decrease in DNA methylation in patients with stable disease or in those who responded to chemotherapy; this decrease was not found in patients whose disease progressed or who did not respond to treatment.
- In addition, the researchers tested the gene panel used in the cMethDNA assay against samples from The Cancer Genome Atlas, a catalog of genes in various cancer types, finding that the gene panel may also be useful in detecting recurrent lung or colorectal cancers but not as accurate in detecting recurrent ovarian, kidney or stomach cancers.
- There is a patent pending on this test.
For more information: The Journal of Cancer Research, doi: 10.1158/0008-5472.CAN-13-3392 Cancer Res April 15, 201474; 2160, Novel Methylated Biomarkers and a Robust Assay to Detect Circulating Tumor DNA in Metastatic Breast Cancer
3. Genetic link discovered for invasive lobular cancer
- Invasive lobular carcinoma, a sub-type of breast cancer which is particularly difficult to diagnose, accounts for between 10 and 15 per cent of all breast cancer cases.
- Researchers at the Institute of Cancer Research have now found a genetic link in the DNA of patients with the condition. Women with the genetic variant rs11977670 were found to be 13 per cent more likely to develop the disease than those without.
- Interestingly, the specific variant is close to a known cancer-causing gene called BRAF, and to a gene involved in the activation of other genes called JHDM1D.
For more information: PloS Genetics, April 17, 2014, DOI: 10.1371/journal.pgen.1004285, Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast (this is an open access article)
4. Link between tissue stiffness and aggressive breast cancer found
- A study by University of Toronto researchers has linked the stiffness of breast tissue to the progression of a particularly aggressive form of breast cancer.
- Back in 2010, the researchers discovered a vital link between the presence of a particular protein, HOXA9 and production of the BRCA1 protein.
- When mutated, the BRCA1 protein malfunctions and can trigger particularly deadly forms of breast cancer.
- HOXA9 makes more BRCA1, which [in its non-mutated state] is a tumor suppressor
- A population of women who didn’t have BRCA1 mutation could have breast tumors that very much resembled those with a BRCA1 mutation.
- Low levels of HOXA9 were most commonly observed in these types of breast tumors and correlated with higher likelihood of metastasis as well as a significantly higher incidence of relapse.
- The study may help clinicians differentiate between aggressive forms of the disease, which tend to have a poor prognosis, and less deadly forms.
For more information: Nature Medicine 20, 360–367 (2014) doi:10.1038/nm.3497, Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression
5. Tumor suppressor protein linked to longer survival times for Triple-Negative Breast Cancer
- ZYMND11, a tumor-suppressing protein acts as a dimmer switch to dial-down gene expression.
- ZYMND11 does this by reading a chemical message attached to another protein (a histone variant protein) that’s tightly intertwined with DNA
- The study, for the first time, identifies a novel role of a histone variant protein in regulating gene transcription aside from its established role.
- This variant, H3.3, is modified by methylation to create a specific epigenetic landscape that is accommodated by the tumor-suppressing protein ZMYND11. The protein in turn blocks gene activation,
- Methylation, the attachment of a methyl group to a gene or protein, and other types of histone modifications are considered epigenetic factors, which modify a gene’s behavior without changing its DNA coding.
- The protein ZMYND11 reads the modified histone H3.3 by connecting to it where a tri-methyl chemical group binds to H3.
- Researchers found that high expression of the tumor-suppressor ZMYND11 is associated with longer survival for patients with triple-negative breast cancer.
- An analysis of ZMYND11 levels in the tumors of 120 triple-negative breast cancer patients showed that those with high levels of the protein had an 80% probability of surviving for 10 years while those with low levels had a 50% probability.
For more information: Nature (2014) doi:10.1038/nature13045, ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression
6. Virus-fighting genes linked to breast cancer mutations
- Researchers at the Wellcome Trust Sanger Institute have found evidence that confirms the role of a group of virus-fighting genes in cancer development.
- The APOBEC family of genes control enzymes that are believed to have evolved in humans to fight off viral infections.
- Scientists have speculated that these enzymes are responsible for a very distinct signature of mutations that is present in approximately half of all cancer types.
- This genetic deletion is found on chromosome 22 where the APOBEC genes, APOBEC3A and APOBEC3B, sit next to each other. Women with this genetic deletion have previously been reported to be more susceptible to breast cancer.
- This genetic deletion is much more prevalent in some populations than others: it is found in only 8 per cent of Europeans, but is present in 93 per cent of the population of Oceania.
- Since the discovery of the first cancer-causing genes in the 1970s, researchers have been eager to catalogue the mutations that can cause cancer.
- Each mutated gene holds the potential to expand our understanding of what causes the disease — and how to treat it.
- The latest progress towards that goal was on display last week, when 18,400 people descended on San Diego in California to attend the annual American Association for Cancer Research meeting.
- Researchers showed how patterns of mutation can be used to track down the agent that caused them — sunlight, for example, leaves a footprint that differs from a cancer-causing viral infection.
- Another team had catalogued cancer-associated mutations in patients with advanced melanoma, hoping to use the information to tailor immune cells to destroy tumours.
- And promising initial results were unveiled on targeting a protein called IDH2, mutations in which crop up in many different tumour types (see Nature 508, 158–159; 2014).
- It has taken a massive effort to make such achievements possible. Seventeen countries have invested in sequencing cancer genomes through the International Cancer Genome Consortium (ICGC), which aims to sequence more than 25,000 samples.
- The largest and oldest component of that project is The Cancer Genome Atlas (TCGA) at the US National Cancer Institute (NCI) in Bethesda, Maryland, which intends to characterize 10,000 tumours.
- But TCGA is now winding down: the project ceased collecting new tissue samples last December.
- The ICGC, too, has virtually stopped accepting proposals for new projects. TCGA aims to complete sequencing and further characterization of its cancer samples by the end of the year.
- After that, a few groups will receive funding to analyse the data for the next two years. But the programme, as it existed, will cease.
- The end of TCGA also represents an opportunity for the field to balance its cancer-genomics projects more evenly between cataloguing mutations and studying their functional significance.
- Functional studies have had short shrift, whereas sequencing — a simple concept, and easier to communicate to policy-makers and the public — has taken the lead. Correcting that imbalance will lead to exciting discoveries for science and for patients.