Curcumin Starves Cancer Cells to Death - by Life Extension

Cancer cells require tremendous energy to promote their rapid growth. A new study shows how curcumin can selectively starve tumor cells.

Winter 2018-2019 Special Edition

By Kirk Stokel

(Previously published here on 7 October 2019)

Over 4,500 published studies describe the anti-cancer effects of curcumin.

Researchers are intrigued by a promising discovery that curcumin selectively starves tumor cells to death.1

Curcumin does this by depriving cancer cells of the ability to make and use ATP, the energy currency within cells.2

Since most cancer cells generate ATP in a different way than healthy cells, curcumin selectively kills tumor cells with no impact on healthy tissues.

These newly uncovered energy-disrupting properties of curcumin further support the preventive potential of this botanical compound.

Cutting Cancer’s Energy Supply

Cancer cells require tremendous energy to promote their rapid, uncontrolled growth, and they have developed numerous methods to support that energy demand.

In particular, cancer cells have an unusual, oxygen-free mechanism of extracting energy from glucose to produce ATP (adenosine triphosphate). This process helps most cancer cells survive in the low-oxygen environments they generate as they grow rapidly.2

Scientists conducted a study to determine if this process can be reversed in cancer cells.

Since many different types of cancer use the same metabolic trick to extract energy, the researchers studied curcumin’s impact on a variety of tumor lines, including leukemia, breast, melanoma (skin), and colon cancers.2

This study shed new light on curcumin’s ability to starve cancer into submission by interfering with how tumors cells use energy.

Let’s look at the findings one at a time.

Curcumin Blocks ATP Production

First, the researchers found that curcumin can sharply reduce how much energy is available to the cancer cells.2

This study showed that curcumin was able to:

1) Reduce levels of ATP-synthase (the enzyme that creates ATP) in all four tumor cell lines in culture,

2) Reduce cellular levels of ATP in three of the four cell lines, and

3) Lower the ratio of high-energy ATP to lower-energy AMP in all four cell lines.

Curcumin Slows Tumor Growth

Next, researchers implanted aggressive skin cancer (melanoma) cells into live mice. Half the mice were treated with curcumin and the other half served as the control group.2

Just 2 days into the study, the curcumin-treated mice were demonstrating significantly slower tumor growth. Tumor growth remained significantly slower for the entire period of the study.

Not surprisingly, ATP-synthase, ATP levels, and the ATP/AMP ratio were all significantly lowered in the curcumin group. These results indicate that energy starvation was a mechanism of action by which curcumin slowed tumor growth.

Curcumin Prevents New Blood Vessel Growth

Cancers need to trigger new blood vessel development (called angiogenesis) to support their nutrient needs as they rapidly grow. Blocking this process is an important way to limit the growth and spread of a tumor.

After removing tumors from the mice in this study, the researchers found that the curcumin-supplemented animals’ tumors had fewer new blood vessels compared with control-fed mice.

This indicates that curcumin reduced the tumors nutrient energy access by limiting blood flow.2

Curcumin’s Known Tumor-Fighting Properties

This most recent study adds to an abundance of evidence pointing to curcumin’s potent cancer-fighting abilities. It focuses on curcumin’s unique ability to combat a variety of cancers by cutting off their energy supply.

Previous studies have shown curcumin’s tumor-fighting properties in multiple specific types of cancer. Here are some highlights from the most recent literature.

Colorectal Cancer

Cancers of the colon and rectum are among the most common malignancies in men and women. Curcumin has a long track record of achievements in preventing colorectal cancers.

A Phase IIa human clinical trial has shown that 4 grams/day of curcumin significantly reduces the number of aberrant crypt foci found during endoscopy. This is a critical finding because if aberrant crypt foci are left untreated, they can produce malignant tumors.3

Weight loss is common in cancer patients. A human study showed that colon cancer patients who were supplemented with curcumin gained more weight, had less inflammation, and had increased numbers of cancer cells dying by apoptosis.4 This effect has been traced to curcumin’s ability to activate a “programmed cell death” gene in tumor cells.

Finally, curcumin has been shown to selectively reduce the survival of cancer stem cells.5 These cells account for much of the metastatic spread and tumor recurrences seen in aggressive malignancies. Cutting their numbers is an appealing approach to preventing tumors from spreading.

While a high-dose (4,000 mg) of curcumin was used in this study, more bioavailable curcumin forms can enable one to achieve a similar dose with two capsules a day.

WHAT YOU NEED TO KNOW

Curcumin Starves Cancer Cells to Death

• Curcumin is a powerful, multi-functional polyphenol that is gaining increasing recognition for its cancer chemopreventive properties.
• A new study shows that curcumin sharply restricts cancer cells’ ability to extract energy from glucose in the blood.
• This mechanism is especially appealing for cancer chemoprevention because it would target the great majority of cancers.
• Previous studies also show that curcumin can reduce inflammation, prevent chemical stress, shut down cancer-promoting pathways, and interfere with malignant cells’ growth and development.
• These multiple mechanisms of action make it clear that curcumin should be a central element of any comprehensive cancer chemoprevention regimen.

Breast Cancer

Breast cancer is the most common cancer in women, and it’s the second leading cause of cancer deaths among women worldwide.6,7

Curcumin has shown promise in combatting breast cancer. This is especially true of estrogen receptor-negative tumors, which respond poorly to cancer chemotherapy.6

Studies show that giving curcumin to animals with implanted human breast cancers shrinks the tumors, deprives them of their blood supply, and triggers their self-destruction by apoptosis.6,8

More recently, research revealed that curcumin can also combat breast cancer by reversing the excessive methylation of certain genes that is associated with increased cancer development.9

Prostate Cancer

Prostate cancer strikes one in nine American men, yet is among the most preventable cancers because of its slow growth.10

Curcumin has multiple actions against prostate cancer. It defends prostate cells against the dysfunctional proteins produced during cancer progression. It also slows invasion of nearby healthy tissue by the cancer, which helps to keep the tumor at a lower grade (meaning it grows more slowly and has a better prognosis).11-13

One study showed that when human prostate cells were implanted into mice, they grew into sizable tumors. But when these animals were supplemented with curcumin, the tumors grew 27% more slowly. In addition, the time it took to double levels of prostate specific antigen (PSA) was extended or delayed by about two-fold.14 (Doubling time is an indicator of how aggressive the cancer is.)

Curcumin can also reduce tumor-derived testosterone production in prostate cancer cells.15 This is a hidden source of male hormones that often contributes to treatment-resistant disease.16 This development offers a welcome new approach to treating these challenging tumors.

Liver Cancer

Liver cancer is increasing in incidence worldwide, spurred by epidemic hepatitis C virus and rampant fatty liver disease.17 

In lab studies, curcumin was shown to help prevent liver cancer by reducing inflammatory signaling, inhibiting cell growth, and activating cell death by apoptosis.18-20 It has also been shown to reduce populations of liver cancer stem cells.19,21

In one study, curcumin inhibited the growth of liver cancer cells, while also promoting their death by apoptosis. And in a mouse model of liver cancer, treatment with curcumin caused the tumors to grow much more slowly.22

And, in an exciting development, a study published in 2018 showed that when curcumin is combined with the AMPK-activator drug metformin, the combination worked better than either alone in preventing growth, metastasis, and new blood vessel formation in hepatocellular carcinoma, the most common—and most deadly—type of liver cancer.23

Lung Cancer

A new study shows that
curcumin sharply restricts
cancer cells’ ability to
extract energy from
glucose in the blood.

Lung cancer continues to be the top cause of cancer-related deaths, making it a huge priority for prevention.24,25

An abundance of animal and basic lab studies show curcumin’s potential against lung cancer.

For example, curcumin has been shown to reduce the growth of implanted human lung cancers in mice.26  Lab studies on lung cancer show that curcumin alters proteins required for metastasis, boosting the function of immune cells that are inactivated by cancers, and targeting blood vessel growth.24,26,27

A unique way in which curcumin combats lung cancer is by modulating microRNA inside cancer cells.28-30 These short stretches of genetic material regulate how the main genes in tumor cells are translated into functional proteins.

Studies reveal that curcumin inhibits lung cancer cell growth by downregulating a gene that promotes tumor formation, while upregulating genes that suppress transformation.28 Other research shows similar favorable modulation of miRNAs involved in metastatic spread.30

Summary

Curcumin is the polyphenol that gives the yellow color to the spice turmeric. It has been front and center in the scientific press for years—mostly recognized for its ability to suppress inflammation.2,31,32

Curcumin has also been shown to prevent cancer progression through a variety of mechanisms. Most recently, a study found that curcumin starves cancer cells of much-needed energy.

This mechanism is especially appealing for cancer prevention because it would target the great majority of cancers.

This confirms previous studies showing that curcumin has specific effects against colorectal, breast, prostate, lung, and liver cancers.

Starving malignant cells of their energy supply is an ideal way of boosting our bodies’ natural cancer resistance, helping it quench cancer long before a tumor is detectable.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

1. Available at: https://www.ncbi.nlm.nih.gov/pubmed/?term=curcumin+and+cancer. Accessed September 21, 2018.
2. Bianchi G, Ravera S, Traverso C, et al. Curcumin induces a fatal energetic impairment in tumor cells in vitro and in vivo by inhibiting ATP-synthase activity. Carcinogenesis. 2018 Sep 21;39(9):1141-50.
3. Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila). 2011 Mar;4(3):354-64.
4. He ZY, Shi CB, Wen H, et al. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. 2011 Mar;29(3):208-13.
5. James MI, Iwuji C, Irving G, et al. Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett. 2015 Aug 10;364(2):135-41.
6. Bimonte S, Barbieri A, Palma G, et al. Dissecting the role of curcumin in tumour growth and angiogenesis in mouse model of human breast cancer. Biomed Res Int. 2015;2015:878134.
7. Wang Y, Yu J, Cui R, et al. Curcumin in Treating Breast Cancer: A Review. J Lab Autom. 2016 Dec;21(6):723-31.
8. Ferreira LC, Arbab AS, Jardim-Perassi BV, et al. Effect of Curcumin on Pro-angiogenic Factors in the Xenograft Model of Breast Cancer. Anticancer Agents Med Chem. 2015;15(10):1285-96.
9. Kumar U, Sharma U, Rathi G. Reversal of hypermethylation and reactivation of glutathione S-transferase pi 1 gene by curcumin in breast cancer cell line. Tumour Biol. 2017 Feb;39(2):1010428317692258.
10. Available at: https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Accessed September 24, 2018.
11. Sundram V, Chauhan SC, Ebeling M, et al. Curcumin attenuates beta-catenin signaling in prostate cancer cells through activation of protein kinase D1. PLoS One. 2012;7(4):e35368.
12. Liu T, Chi H, Chen J, et al. Curcumin suppresses proliferation and in vitro invasion of human prostate cancer stem cells by ceRNA effect of miR-145 and lncRNA-ROR. Gene. 2017 Oct 5;631:29-38.
13. Yang J, Wang C, Zhang Z, et al. Curcumin inhibits the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway. APMIS. 2017 Feb;125(2):134-40.
14. Hong JH, Lee G, Choi HY. Effect of curcumin on the interaction between androgen receptor and Wnt/beta-catenin in LNCaP xenografts. Korean J Urol. 2015 Sep;56(9):656-65.
15. Ide H, Lu Y, Noguchi T, et al. Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer. Cancer Sci. 2018 Apr;109(4):1230-8.
16. Armandari I, Hamid AR, Verhaegh G, et al. Intratumoral steroidogenesis in castration-resistant prostate cancer: a target for therapy. Prostate Int. 2014 Sep;2(3):105-13.
17. Global Burden of Disease Liver Cancer C, Akinyemiju T, Abera S, et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015. JAMA Oncol. 2017 Dec 1;3(12):1683-91.
18. Dai XZ, Yin HT, Sun LF, et al. Potential therapeutic efficacy of curcumin in liver cancer. Asian Pac J Cancer Prev. 2013;14(6):3855-9.
19. Marquardt JU, Gomez-Quiroz L, Arreguin Camacho LO, et al. Curcumin effectively inhibits oncogenic NF-kappaB signaling and restrains stemness features in liver cancer. J Hepatol. 2015 Sep;63(3):661-9.
20. Elmansi AM, El-Karef AA, Shishtawy M, et al. Hepatoprotective Effect of Curcumin on Hepatocellular Carcinoma Through Autophagic and Apoptic Pathways. Ann Hepatol. 2017 Jul-Aug;16(4):607-18.
21. Tsai CF, Hsieh TH, Lee JN, et al. Curcumin Suppresses Phthalate-Induced Metastasis and the Proportion of Cancer Stem Cell (CSC)-like Cells via the Inhibition of AhR/ERK/SK1 Signaling in Hepatocellular Carcinoma. J Agric Food Chem. 2015 Dec 9;63(48):10388-98.
22. Pan Z, Zhuang J, Ji C, et al. Curcumin inhibits hepatocellular carcinoma growth by targeting VEGF expression. Oncol Lett. 2018 Apr;15(4):4821-6.
23. Zhang HH, Zhang Y, Cheng YN, et al. Metformin incombination with curcumin inhibits the growth, metastasis, and angiogenesis of hepatocellular carcinoma in vitro and in vivo. Mol Carcinog. 2018 Jan;57(1):44-56.
24. Liu D, You M, Xu Y, et al. Inhibition of curcumin on myeloid-derived suppressor cells is requisite for controlling lung cancer. Int Immunopharmacol. 2016 Oct;39:265-72.
25. Available at: https://www.cancer.org/latest-news/facts-and-figures-2018-rate-of-deaths-from-cancer-continues-decline.html. Accessed September 24, 2018.
26. Chen QY, Jiao DM, Yao QH, et al. Expression analysis of Cdc42 in lung cancer and modulation of its expression by curcumin in lung cancer cell lines. Int J Oncol. 2012 May;40(5):1561-8.
27. Xu X, Zhu Y. Curcumin inhibits human non-small cell lung cancer xenografts by targeting STAT3 pathway. Am J Transl Res. 2017;9(8):3633-41.
28. Lelli D, Pedone C, Majeed M, et al. Curcumin and Lung Cancer: the Role of microRNAs. Curr Pharm Des. 2017;23(23):3440-4.
29. Liu WL, Chang JM, Chong IW, et al. Curcumin Inhibits LIN-28A through the Activation of miRNA-98 in the Lung Cancer Cell Line A549. Molecules. 2017 Jun 3;22(6).
30. Zhan JW, Jiao DM, Wang Y, et al. Integrated microRNA and gene expression profiling reveals the crucial miRNAs in curcumin anti-lung cancer cell invasion. Thorac Cancer. 2017 Sep;8(5):461-70.
31. Chadalapaka G, Jutooru I, Chintharlapalli S, et al. Curcumin decreases specificity protein expression in bladder cancer cells. Cancer Res. 2008 Jul 1;68(13):5345-54.
32. Kelany ME, Hakami TM, Omar AH. Curcumin improves the metabolic syndrome in high-fructose-diet-fed rats: role of TNF-alpha, NF-kappaB, and oxidative stress. Can J Physiol Pharmacol. 2017 Feb;95(2):140-50.

Turmeric - This Spice Stops Cancer, Study Finds

Prostate cancer is so common in the U.S. that screening is a standard part of men’s checkups. In India, prostate cancer is so rare that it’s not even a concern.

American men get 23 times more prostate cancer than men in India.

by Garry MessickNovember 10, 2019

The story is similar for breast cancer. American women get five times more breast cancer than women in India.[1]

Here’s how the U.S. stacks up to India regarding other cancers:[2]

• 17 times more lung cancer

• 14 times more melanoma

• 12 times more kidney cancer

• 11 times more colon cancer

• 9 times more endometrial cancer

• 8 times more bladder cancer

Scientists believe they’ve discovered India’s anti-cancer secret: turmeric, the yellow powder used in curry dishes.

It is a staple food in the country. People in many parts of India eat it in every meal.

Now, new research shows how turmeric and curcumin, its active ingredient, stop cancer on a molecular level.

The study comes from Japan’s Nara Institute of Science and Technology. The research team looked at a molecule called pentagamavumon-1 (PGV-1). PGV-1 is very similar to a molecule found in curcumin.[3]

The study found that PGV-1 suppresses enzymes that protect cancer cells, causing the cells to die.

The curcumin-derived molecule was effective against a wide range of cancers.

Investigators implanted human cancer cells in mice. When injected with PGV-1, the rodents’ cancer was entirely destroyed.

Professor Jun-ya Kato lead the study. He said that considering the stunning effectiveness and “low amounts of side effects,” PGV-1 should be used to treat cancer.

Previous studies provide strong evidence that curcumin is powerful medicine against cancer:

• UCLA researchers found in 2011 that curcumin activates cancer-fighting enzymes in patients with head and neck cancers.[4]

• A 2013 study at the University of North Texas Health Science Center found that curcumin suppresses pancreatic cancer tumors.[5]

• A 2006 study published in the journal Neuroscience Letters found that curcumin induces cell death in glioblastoma (brain cancer) cells.[6]

• A Chinese study showed that curcumin makes stomach cancer less resistant to chemotherapy.[7]

• A study at MD Anderson Cancer Center showed that curcumin slowed the progression of multiple myeloma (blood cancer).[8]

With all this evidence (and this is by no means a complete list) you may be wondering why curcumin isn’t widely prescribed for the prevention and treatment of cancer.

Curcumin: India’s Anti-Cancer Secret

People in India get curcumin by eating turmeric at almost every meal. Most Americans are not willing to do this. That’s why, for most of us, curcumin supplements are the best option for cancer prevention.

Curcumin is safe for just about everyone. However, people taking blood thinners such as Coumadin (warfarin) should consult their doctor. Curcumin can increase the effect of Coumadin and other similar drugs.

Curcumin by itself is not easily absorbed by the body. Fat increases bioavailability. So taking curcumin with a meal that includes fat improves absorption.

In the war on cancer, mainstream medicine’s main weapons are surgery, chemo, and radiation. They often do more harm than good.

India clearly has a better answer…a safe, natural way to stop one of our deadliest health problems.

Editor’s Note: If you’re worried about cancer, you need to read our monthly journal, Independent Healing. It’s your best source for unbiased, evidence-based medical advice. Discover The Cancer Kill Code. It’s a secret natural trigger that detonates cancer’s self-destruct button.

Find out more HERE.

Related Articles

The Puerto Rican Anti-Cancer Secret

Pancreatic Cancer Disappeared in 70% of Mice Treated With Cannabis

Curcumin Treats Burns and Heals Skin, Scientists Find

[1]http://www.greenmedinfo.com/article/curcumin-induces-apoptosis-triple-negative-breast-cancer-cells

[2]https://nutritionfacts.org/2015/05/05/why-are-cancer-rates-so-low-in-india/

[3]https://www.nature.com/articles/s41598-019-51244-3

[4]https://www.theatlantic.com/health/archive/2011/09/turmeric-the-potential-cure-for-cancer-found-in-indian-food/245115/

[5]http://www.greenmedinfo.com/article/efficacy-liposomal-curcumin-human-pancreatic-tumor-xenograft-model-inhibition

[6]http://www.greenmedinfo.com/article/efficacy-liposomal-curcumin-human-pancreatic-tumor-xenograft-model-inhibition

[7]http://beatcancer.org/blog-posts/curcumin-and-cancer-part-two

[8]http://beatcancer.org/blog-posts/curcumin-and-cancer-part-two

https://www.institutefornaturalhealing.com/2019/11/this-spice-stops-cancer-study-finds/

Gut microbiota may be the reason why cancer immunotherapy works for some but not all

Scientists found 11 bacterial strains and a link to a cellular process in mice that influences whether their immune system fights melanoma.

2nd April 2019

A group of 40 clinicians, computer scientists and microbiome experts say they’ve found a link between the gut microbiome and the immune system’s ability to fight cancer in their new study. 

They showed that mice with certain gut bacteria could fight off melanoma effectively while those without couldn’t. They also showed that mice with these gut bacteria had reduced unfolded protein response – a cellular stress response that can help the cell regain normal protein production but can also lead to cell death, and tumor take-over.

This link is important because the presence of these bacteria strains and reduced UPR could point out who checkpoint blockade immunotherapy, one type of cancer immunotherapy, works for. 

Currently, this therapy only works for half of the patients it’s given to, sometimes stops working after some time, or comes with autoimmune-sickness like side effects. Therefore, it would be helpful to know in advance who would be helped by checkpoint blockade immunotherapy, and who wouldn’t.

We spoke with Ze’ev Ronai at Sanford Burnham Prebys Medical Discovery Institute about the group’s findings as the latest in the hunt for biomarkers in cancer immunotherapy.

ResearchGate: How do immune checkpoint inhibitors work and who do they work for?

Ze’ev Ronai: Immune checkpoint inhibitors “release the breaks” which usually protect tumors from being attacked by the immune system’.

RG: How did you come up with the idea to study the gut microbiome’s influence on cancer immunotherapy?

Ronai: An unexpected observation we made led us to explore the possible role of the gut microbiota in the control of anti-tumor immune response. We noticed that our mice, a genetically modified strain lacking one gene, were able to inhibit melanoma growth. We were surprised to find out that such inhibition was lost when the mice were treated with a cocktail of antibiotics: This implied a possible effect of the gut microbiota which is known to be deregulated following antibiotic treatment. Then we let these mice live together with non-genetically modified mice that didn’t reject the tumor. This co-housing resulted in loss of the tumor rejection phenotype, seen in the mutant mice. Since co-housing is known to affect the microbiota composition, we set to directly assess the possibility that the gut microbiota have a direct role in the activation of the immune system to attack tumors.

RG: How did you study their influence on the gut microbiome?

Ronai: We used a number of computational tools to help us dissect the information gathered from the analysis of the gut microbiota composition of our mice, comparing those that reject tumors to those that do not. This computational approach enabled us to identify a set of 49 bacterial families that were enriched in the mutant mice – which exhibit tumor growth inhibition. Further computational work allowed us to focus on 11 bacterial strains that were then directly tested for their effect on anti-tumor immunity in mice. We grew these select bacterial strains in culture and administered them to mice that lack bacteria in their gut (germ free mice), assessing the impact of these bacterial population.

RG: What did you find?

Ronai: We found that administering these 11 bacterial strains to germ free mice was effective in inducing anti-tumor immune response which limited melanoma growth.

RG: Is there anything special about these 11 bacterial strains? Are they commonly found in our gut?

Ronai: These are commonly found in the gut, some of them were shown to have a positive impact on the immune system and help activating it in context of fighting cancer, others were novel.

RG: What’s next in your research?

Ronai: Mapping the microbiota by-products – metabolites – that could have influence on the anti-tumor immunity – allowing us to cross the barrier from mouse to men.

https://www.researchgate.net/blog/post/gut-microbiota-may-be-the-reason-why-cancer-immunotherapy-works-for-some-but-not-all

Researchers identify a way to stop cancer from spreading

A new study suggests the spread of cancer is tied to dietary fatty acids, including from palm oil, and that blocking a key receptor can prevent it.

7th December 2016

Metastasis, the spreading of cancer cells to other parts of the body, is the main cause of cancer-related death. 

New research has identified the cells responsible for this process in oral tumors, and also a promising way to stop it. The key lies in the cells’ ability to absorb dietary fatty acids—particularly palmitic acid, a major component in palm oil. Metastasis-initiating cells have high levels of the fatty acid receptor CD36 and seem to rely on certain fatty acids to thrive. 

Blocking the CD36 receptor prevented human oral cancer transplanted into mice from spreading, and a similar effect was found in melanoma and breast cancer cells. Senior author Salvador Aznar Benitah of IRB Barcelona tells us more about these promising findings.

Salvador Aznar Benitah and first author Gloria Pascual. Courtesy of IRB Barcelona.

ResearchGate: How did you discover these metastasis-initiating cells?

Salvador Aznar Benitah: This has been an interesting process. Originally, the aim of the project was not at all related to metastasis. We wanted to study whether cancer stem cells that weren’t dividing were responsible for tumor relapse after chemotherapy. We did observe these cells, but when we analyzed their molecular features, it was clear that they expressed very high levels of genes previously shown to induce or support metastasis. They also expressed many genes involved in fatty acid metabolism. In a sense, the cells and their molecular characteristics lead us to studying their role in metastasis, rather than the other way around.

RG: How were you able to stop the spread of cancer?

Benitah: We show by different means that blocking the activity of the fatty acid receptor CD36 has a very strong anti-metastatic effect. We hypothesize that metastatic cells rely so much on the availability of certain fatty acids, that they cannot cope without them. However, we still do not know the precise mechanism of why blocking CD36 results in such a strong effect on metastasis. We are working now to figure that out.

RG: What role does the consumption of fat play in the metastasis of cancer? Does the type of fat matter?

Benitah: The preclinical models in which we transplanted human tumor cells into mice indicate that a high fat diet potently boosts the metastatic potential of the tumors. In particular, we identified palmitic acid, a major component in palm oil, as a main player in this effect. Other fatty acids might also do it, while others might even be protective against metastasis. Very interesting questions arise from these results, and we are actively studying these. One important question would be to determine whether lowering the amount of fatty acids in the diet of patients with metastatic tumors could reduce the incidence of metastasis, or their aggressiveness. Careful experiments will need to be done in order to determine these things in patients.

RG: What do your findings mean for our understanding of cancer?

Benitah: I think this is an important and exciting first step. Now that we have been able to identify these cells responsible for metastasis, we can study their behavior in much more detail. Also, it opens the possibility of a new anti-metastatic therapy based on blocking the ability of these cells to uptake fatty acids. We are working hard to be able to try this.

RG: What would a drug based on this approach mean for our treatment of cancer?

Benitah: We are already developing a blocking antibody against CD36 together with MRCT, a UK-based non-profit company, that we hope to test in clinical trials in patients as soon as possible. We hope that this treatment, combined with the treatments already available for patients with these aggressive forms of cancer, may result in better clinical responses, and a better quality of life.

RG: When do you hope to begin clinical trials of this antibody in humans?

Benitah: It is very hard at this stage to know when we could start the clinical trials, but if everything goes alright we hope to start them within the next 5 years. This would be indeed very good news.

Featured image: Breast cancer cells. Courtesy of the National Cancer Institute and Cecil Fox.

ttps://www.researchgate.net/blog/post/researchers-identify-a-way-to-stop-cancer-from-spreading

When Cancer Spreads to the Brain: New Treatments Offer Hope

Some patients are living up to seven times longer than before. Here’s how…

Nduka Amankulor, MD, a neurosurgeon and neuro-oncologist at UPMC Hillman Cancer Center and assistant professor of neurological surgery at University of Pittsburgh School of Medicine.

CANCER

Published Date: October 1, 2019

Publication: Bottom Line Health

CANCER

When Cancer Spreads to the Brain: New Treatments Offer Hope

When melanoma or some other cancer spreads to the brain, the prognosis used to be grim. Now, treatment advances are dramatically improving outcomes…

An astounding 20% to 30% of people with cancer develop metastatic brain cancer (MBC)—cancer that has spread from another organ to the brain.

Breast cancer, lung cancer, kidney cancer and melanoma are the main types of cancer that invade the brain. But almost any cancer can produce brain metastases, with an estimated 170,000 new cases every year. 

Until recently, the prognosis for people with MBC was grim—only 8% of patients were alive two years after diagnosis, and 2% after five years. But those sad statistics are changing.

Now: The treatment of MBC is being revolutionized by targeted drug therapies that attack genetic mutations driving cancer…immunotherapies that stimulate the body’s own immune system to fight cancer…and precisely focused radiation.

Immunotherapy more than doubled the average survival time of melanoma­ patients with MBC—from 5.2 months to 12.4 months, according to a study published in Cancer Immunology Research. The effects are even better for melanoma patients with MBC but no other metastases—research found that those who received immunotherapy had an average survival rate of 56 months, compared with 7.7 months for those receiving standard treatment, such as chemotherapy. In other words, MBC patients treated with immunotherapy lived about seven times longer!  

What cancer patients and their families need to know…

Early Detection

Many oncologists don’t recommend screening for brain metastases, except for certain tumor types that have a significant predilection for spreading to the brain. Of course, if the patient develops neurological symptoms, such as headaches, numbness, blurred vision, balance difficulties, cognitive decline and/or seizures, then brain screening for a brain tumor is recommended, regardless of the type of cancer. 

New thinking: Early detection can extend survival time in patients without neurological symptoms who are at high risk of developing MBC. 

My advice for who should get screened… 

• Any patient with a new diagnosis of stage II to stage IV lung cancer, whether it’s non-small cell (the most common type) or small cell. 

• A melanoma patient with metastatic disease elsewhere in the body—because two out of three of these patients will also develop MBC. 

• A breast cancer patient who is positive for HER2 (a gene that plays a role in the development of breast cancer)…or whose tumor lacks hormone receptors (estrogen and progesterone receptors)…or lacks any markers at all (triple-negative breast cancer). The rate of MBC is significantly higher (10% to 15%) in all these breast cancer patients.

The gold standard for early detection is a brain MRI with contrast dye, which can detect brain tumors as small as 2 millimeters in diameter (less than one-tenth of an inch). Especially in patients who are at high risk of developing MBC, insurance may cover the MRI even if there are no neurological symptoms, but be sure to check first. Once MBC is diagnosed, MRIs are obtained roughly every two to four months.

Targeted Therapies

Targeted therapies are drugs (oral or IV) that block or alter specific genes and/or proteins that drive cancer. There have been dozens of clinical trials of targeted therapy in patients with brain metastases—with some remarkable results. For example…

Researchers from the MD Anderson Cancer Center at University of Texas studied melanoma patients with MBC who had the BRAF mutation, which occurs in about half of patients with this disease. The patients received two drugs—dabrafenib (Tafinlar), which targets BRAF…and trametinib (Mekinist), which targets MEK, a mutation similar to BRAF. In a group of 76 patients with BRAF who had never been treated for MBC and whose neurological symptoms were under control, 58% had significant shrinking of their brain tumors—and in four patients the tumors vanished, according to the research, which was published in The Lancet Oncology. The response lasted, on average, six to seven months. 

Immunotherapy

Immunotherapy drugs are a class of drugs that stimulate a patient’s immune system, essentially calling it into action. The most widely used immunotherapies are drugs that block checkpoint proteins, such as PD-1 or PD-L1, which suppress inflammatory responses in the immune system.

Scientific evidence: Impressive results with combined drug therapy—ipilimumab (Yervoy) and nivolumab (Opdivo)—were cited in a study published in The New England Journal of Medicine. In that research, when 94 melanoma patients with MBC took both drugs, 81% were alive after one year and 70% after two years—a dramatic increase over the typical survival rate of four to five months before the introduction of immunotherapy. 

Focused Radiation

In the past, the standard radiation treatment for MBC was whole-brain radiation—multiple treatments of the entire brain with low-dose radiation. 

However, whole-brain radiation has significant side effects, such as a marked decrease in memory and other cognitive abilities. Doctors are now using highly focused radiation therapies called stereotactic radiosurgery. Employing a flexible robotic arm to deliver radiation (CyberKnife), or using a helmet with built-in radiation sources (Gamma Knife), this treatment delivers less total radiation…faster…and more accurately. And its cancer-killing efficacy is as good as whole-brain radiation —with less severe side effects.

Your Plan of Action

To take advantage of the breakthrough treatments for MBC, you need a plan of action. Here are four steps to follow…

STEP  #1: Treat the primary cancer. The key in treating cancer is always minimizing your overall cancer burden using the full range of treatments available—such as chemotherapy, radiation, surgery, targeted therapies and immunotherapy. Controlling the primary malignancy reduces the risk of the cancer spreading to the brain. 

STEP #2: Ask your oncologist, “Has my tumor been sufficiently molecularly characterized?” Sophisticated genetic tests will show if you’re a candidate for targeted therapy or immunotherapy.

For example, if such testing shows that you have the ALK mutation, treatments for the primary tumor may include targeted therapies such as alectinib (Alecensa), brigatinib (Alunbrig) or lorlatinib (Lorbrena)—all of which also help prevent and/or treat brain metastases.

If a tumor biopsy shows that you have high levels of PD-1 or PD-L1, then you may be a candidate for an immunotherapy drug such as pembrolizumab (Keytruda), nivolumab (Opdivo) or atezolizumab (Tecentriq).  

STEP #3: Ask your oncologist, “Are there effective therapies that treat the molecular pathways affecting my cancer—and should we use those therapies to treat my brain cancer?” Once your tumor has been tested for molecular mutations, talk with your oncologist about the targeted and immunological therapies available to treat those problems. You and your doctor should develop a complete list of the targeted therapies and immunotherapies (see examples above) that may be right for you—and then decide which to use.

STEP #4: Demand a multidisciplinary team approach. The best treatment for primary cancer and for MBC is a team approach, typically involving a medical oncologist, a radiation oncologist and a cancer surgeon. The best treatment decisions are made when the entire team talks to one another, face-to-face. This type of multidisciplinary approach is typical of cancer centers that are designated by the National Cancer Institute for offering cutting-edge treatments. To find such an NCI-designated cancer center near you, go to: Cancer.gov/research/nci-role/cancer-­centers/find.

https://bottomlineinc.com/health/cancer/when-cancer-spreads-to-the-brain-new-treatments-offer-hope