CT-guided biopsy of progressing lung lesions after 10 months on gefitinib
In the same way that antibiotics tend to encourage bacteria to mutate, in the same way, chemotherapy promotes cancer resistance via different action mechanisms.
What Is Chemotherapy Resistance?
Chemotherapy resistance occurs when cancers that have been responding to a therapy suddenly begin to grow. In other words, the cancer cells are resisting the effects of the chemotherapy. You may hear statements like the "cancer chemotherapy failed." When this occurs, mainstream oncologists change chemo drugs.
There are several possible reasons for chemotherapy resistance:
- Some of the cells that are not killed by the chemotherapy mutate (change) and become resistant to the drug. Once they multiply, there may be more resistant cells than cells that are sensitive to the chemotherapy.
- Gene amplification. A cancer cell may produce hundreds of copies of a particular gene. This gene triggers an overproduction of protein that renders the anticancer drug ineffective.
- Cancer cells may pump the drug out of the cell as fast as it is going in using a molecule called p-glycoprotein.
- Cancer cells may stop taking in the drugs because the protein that transports the drug across the cell wall stops working.
- The cancer cells may learn how to repair the DNA breaks caused by some anti-cancer drugs.
- Cancer cells may develop a mechanism that inactivates the drug.
Research is underway to investigate ways of reducing or preventing chemotherapy resistance.
The development of drug resistance is one reason that drugs are often given in combination. It is thought that this may reduce the incidence of developing resistance to any one drug. Often, if a cancer becomes resistant to one drug or group of drugs, it is more likely that the cancer may be resistant to other drugs. This is why most mainstream oncologists select the strongest possible treatment protocol first.
Why do some drugs work for some patients and not for others?
The reason why the cancer cells become resistant has to do with mutations or changes in their genetic material. As they divide, cells become progressively more derailed in the way their genetic material works and the more this process takes place, the more these cells become oblivious to the presence of these drugs around.
These genes are important in terms of telling the cell what to do, telling the cell how to behave. When this gene changes because of so many divisions and so many mutations, then the behavior of the cell becomes completely abnormal and that leads to resistance to drugs that normally kill cells. source
Combination of natural diet and chemotherapy is new recipe for cancer treatment
Research in the Linus Pauling Institute at Oregon State University suggests that some natural food compounds, which previously have been studied for their ability to prevent cancer, may be able to play a more significant role in treating it – working side-by-side with the conventional drugs that are now used in chemotherapy.
A new study just published in the International Journal of Cancer examined the activity of chlorophyllin and found that, on a dose-by-dose basis, it was 10 times more potent at causing death of colon cancer cells than hydroxyurea, a chemotherapeutic drug commonly used in cancer treatment.
Beyond that, chlorophyllin kills cancer cells by blocking the same phase of cellular division that hydroxyurea does, but by a different mechanism. This suggests that it – and possibly other "cocktails" of natural products – might be developed to have a synergistic effect with conventional cancer drugs, helping them to work better or require less toxic dosages, researchers said.
"We conclude that chlorophyllin has the potential to be effective in the clinical setting, when used alone or in combination with currently available cancer therapeutic agents," the researchers wrote in their study.
The concept of combining conventional or new cancer drugs with natural compounds that have been shown to have anti-cancer properties is very promising, said Rod Dashwood, professor and director of the Cancer Chemoprotection Program in the Linus Pauling Institute.
"Most chemotherapeutic approaches to cancer try to target cancer cells specifically and do something that slows or stops their cell growth process," Dashwood said. "We're now identifying such mechanisms of action for natural compounds, including dietary agents. With further research we may be able to make the two approaches work together to enhance the effectiveness of cancer therapies."
Chlorophyllin is a water-soluble derivative of chlorophyll – the green pigment source
ANTI OXYDANTS AND CHEMO THERAPY
Common practice in oncology is to denigrate the use of antioxidants in combination
with chemotherapy. This is because antioxidants supposedly negate the free radical
formation at the mitochondria which in turn causes apoptosis to the tumour cell.
However, it is this unopposed free radical formation that stimulates inflammation and
the activity of transcription factors such as NF Kappa B that lead to its long term
failure. NF Kappa B is effectively inhibited by natural substances such as Green Tea
and Genistein whilst supporting the apoptotic effect of chemotherapy.2345678
Professor Avni Sali from Swinburne University in Melbourne, when asked about the
results of a Meta analysis of randomised studies comparing the use of antioxidants,
said different authors seem to be coming up with different results.
My reading of the situation is that certain antioxidants such as Vitamin A and possibly
Vitamin E are not helpful and these antioxidants have no place in oncology practice.
However, there is no evidence in my opinion that other antioxidants have a negative
effect. On the contrary some of the studies on antioxidant trials conclude the use of
antioxidants is helpful in conjunction with other cancer treatments. The evidence
points to a decrease in side effects, the possibility of longer sustained chemotherapy
with higher doses while some studies suggest improved long term outcomes.91011121314
In the latest review by Block et al, published in INTJ cancer in May 2008, he states
“Our analysis suggested in fact that the concurrent use of supplements and
chemotherapy treatments might produce better tumour responses and increased
survival.”15
So why are patients, knowing the dismal results of long term chemotherapy and
requesting to use some form of natural therapy in conjunction with chemotherapy met
with such resistance and contempt? If there was clear evidence of harm from natural
therapy this would be understandable. However no such evidence exists, except for
the two antioxidants mentioned above.
I have spent the last twenty years studying the effects of natural therapies in cancer. I
belong to the College of Nutrition and Environmental Medicine. This college teaches
nutrition to Doctors and allied professionals.
Biochemistry and nutrition are taught minimally in medical school and I believe
strongly that postgraduate training in nutrition as provided by the College of Nutrition
and Environmental Medicine is a necessary requirement to fill this gap
.
The basis of abnormal cell functioning is aberrant biochemical functioning. The
advances in biochemistry, molecular biology, cell signalling chemistry and cell
receptor chemistry have been huge in the last eight years. Any reading of this material
will show the enormous research that has gone into the use of natural substances in
medicine.
There is a large proportion of the public that want an integrated approach using
natural medicines alongside conventional pharmacology. Denigrating the doctors
who can provide this and are trained in this area only creates division. The result will
be a further movement of patients into the non medical world of untrained
practitioners where there is little regulation.
I would like to see more interaction in this area for the benefit of the patients. I invite
more informed discussion on natural medicine’s role in oncology so that patients are
not caught up in the middle where they will not benefit. All members of the medical
profession, including those who believe that natural substances have a role to play in
the care of cancer patients, should be invited to develop strategies and discuss pro’s
and con’s and thus provide the best information that patients can then use to make a
decision regarding their own treatment. source
1 The Contribution of Cytotoxic Chemotherapy to 5 year Survival in Adult Malignancies.
Graeme Morgan*, Robyn Ward, Michael Barton
Clinical Oncology (2004) 16: 549 – 560 doi: 10.1016/j.clon.2004.06.007
2 Inhibition of Nuclear Factor kB Activation in PC3 Cells by Genistein is Medicated via Akt Signalling
Pathway
Yiwei Li, Fazlul H. Sarkar. Department of Pathology, Karmanos Cancer Institute, Wayne State
University School of Medicine, Detroit, Michigan 48201
3 Cisplatin up-regulates ICAM-1 expression in endothelial cell via a NF-kappaB dependant pathway.
Yu M, Han J, Cui P, Dai M, Li H, Zhang J, Xiu R.
http://www.ncbi.nlm.nih.gov/pubmed/18271937?ordinalpos=2&itool=EntrezSystem2
4 Apoptosis-inducing effect of chemotherapeutic agents is potentiated by soy isoflavone genistein, a
natural inhibitor of MF-kappaB in BxPC-3 pancreatic cancer cell line.
Li Y, Ellis KL, Ali S, El-Rayes BF, Nedeljkovic-Kurepa A, Kucuk O, Philip PA, Sarkar FH.
Http://www.ncbi.nlm.nih.gov/pubmed/15097869?dopt=Abstrct
5 Inactivation of Nuclear Factor kB by Soy Isoflavone Genistein Contributes to Increased Apoptosis
Induced by Chemotherapeutic Agents in Human Cancer Cells.
Yiwei Li, Fakhara Ahmed, Shadan Ali, Philip A. Philip, Omer Kucuk, and Fazlul H. Sarkar
Cancer Res 2005; 65: (15) August 1, 2005, www.aacrjournals.org
CALORIC RESTRICTION AND CHEMO RESISTANCE
Doctors who treat patients with cancer have a balancing act. They give too little chemotherapy and tumors survive, but too much can be life threatening. Now researchers have found that in a series of lab tests, not eating for 48 hours gave healthy cells an edge. University of Southern California Associate Professor of Gerontology and Biological Science Valter Longo says, "The cancer cells have this oncogene, have these mutations that keep them always on. So, they basically are unable to obey the starvation dependent order. Starvation tells [healthy cells] to go into protective mode. The cancer cells, because of their characteristics of not being able to respond to that, just continue on their normal pro-growth track."Longo notes that, "Virtually all cancer research is focused on…the killing of the cancer cells," but that he wanted instead to see if there was a way to give the healthy cells an edge.
Scientists know from experiments with everything from tiny worms to primates that a lack of food sends cells into a protective mode that can actually extend life. In fact, Longo says his former college advisor helped pioneer this concept of "calorie restriction." Longo describes it as "fasting, not completely, but partially for a long time."Longo says however, "The cancer cells have these oncogenes, these mutations, that keep them always on (so that they) continue on their pro-growth track" even when the healthy cells have shut down due to a lack of food.
With the healthy cells in protective mode, Longo was able to use more chemotherapy. He wrote in The Proceedings of the National Academy of Sciences he performed several different tests.
One test involved yeast cells that were both subject to starvation and genetically altered to mimic having the starvation condition. They were 1,000 times better protected against cancer-fighting agents. He also tested normal brain cells and cancerous cells in test tubes and found that the normal cells that were denied normal levels of glucose were protected against several forms of chemotherapy while the cancerous cells were not.
In a third experiment on mice that were starved for 48 hours before chemotherapy, Longo says, "The animals were running around after at least a three-fold higher dose than the maximum…allowed for patients." Source
INSULIN POTENTIATION THERAPY AND CHEMO RESISTANCE
More later
BOTANICALS AND CHEMO RESISTANCE
More later
HEAT AND CHEMO RESISTANCE
More later
Lifestyle change and exercises and chemo resistance
STUDY ON LUNG CANCER AND CHEMO RESISTANCE
The drugs are so-called kinase inhibitors and inhibit the epidermal growth factor receptor (EGFR) kinase molecule. Both of them, gefitinib (Iressa) and erlotinib (Tarceva), have shown therapeutic benefits in a subset of patients with lung cancer. Recent work has helped to understand why some patients respond and some don't: responsive tumors usually harbor activating mutations in the EGFR gene, which somehow make the tumors sensitive to treatment. Nearly all patients whose tumors initially respond to the drugs, however, eventually become resistant to the drugs and progress despite continued therapy.
In this study, the scientists examined tumors from six patients with non-small cell lung cancer who initially responded to gefitinib or erlotinib but subsequently relapsed. Tumors from all six patients carried activating mutations in the EGFR gene. In addition, in three out of the six cases, the resistant tumor cells carried an identical second mutation in the EGFR gene. Whereas the activating mutation was present in tumor cells before treatment with erlotinib or gefitinib, the second mutation was not found in pre-treatment biopsies from these patients, nor in over 150 lung cancer samples from patients who had not been treated with either drug. Additional cell culture studies supported the notion that the secondary mutation causes resistance to gefitinib or erlotinib. It is clear, though, that this is only one of several resistance mechanisms, because in the three other cases resistance occurred in the absence of the second mutation. What caused the resistance in those tumors is not known.
All kinases share some common features, and a resistance mutation very similar to the one identified here has also been found in other kinase genes from tumors with acquired resistance to imatinib, another kinase inhibitor. As Gary Gilliland and colleagues point out in an accompanying Perspective article, the initial identification three years ago of resistance mutations against imatinib led to the rapid development of alternative kinase inhibitors that work even against tumors with the resistance mutation. Similarly, the results by Pao and colleagues should help researchers develop second generation drugs for lung cancer.
Citation: Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, et al. (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. 2(3): e73.
On the nefarious effects of most antibiotics and how the suppression of antibiotics and the promotion of natural hygiene has "cured" the staph epidemic in Norway
" Twenty-five years ago, Norwegians were also losing their lives to this bacteria. But Norway's public health system fought back with an aggressive program that made it the most infection-free country in the world. A key part of that program was cutting back severely on the use of antibiotics.
Now a spate of new studies from around the world prove that Norway's model can be replicated with extraordinary success, and public health experts are saying these deaths — 19,000 in the U.S. each year alone, more than from AIDS — are unnecessary.
"It's a very sad situation that in some places so many are dying from this, because we have shown here in Norway that Methicillin-resistant Staphylococcus aureus (MRSA) can be controlled, and with not too much effort," said Jan Hendrik-Binder, Oslo's MRSA medical adviser. "But you have to take it seriously, you have to give it attention, and you must not give up."
The World Health Organization says antibiotic resistance is one of the leading public health threats on the planet. A six-month investigation by The Associated Press found overuse and misuse of medicines has led to mutations in once curable diseases like tuberculosis and malaria, making them harder and in some cases impossible to treat".
source
REREFENCE AND AVENUES OF RESEARCH
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