Bepaalde medicijnen bij kanker wellicht niet zo goed*
Angiogeneseremmers zijn medicijnen die de vorming van nieuwe bloedvaten
(angiogenese) tegengaan. Bij het groeien van kankergezwellen ontstaan ook nieuwe bloedvaten om het nieuwe weefsel van bloed te voorzien. Door het ontstaan van nieuwe bloedvaten moeilijk te maken wordt ook de groei van tumoren onderdrukt. Doch door deze medicijnen worden ook het aantal pericytcellen met wel 70% verminderd. (De pericyten zijn rond de vaten gewikkeld en zorgen voor de stevigheid van de vaten en een vermindering van het aantal pericyten zorgt voor een minder stevig bloedvat en een doorbreken van de binnenste
bloedbarričre wat voor lekkages in de vaten zorgt.) Door die vermindering van het aantal pericytcellen zo blijkt uit deze studie, zowel bij muizen als bij onderzoek van menselijk borstkankerweefsel, dat daardoor de kans op uitzaaiingen wel met 300% toeneemt. Weliswaar zorgen
angiogeneseremmers voor een afname van het kankergezwel doch ook voor aanzienlijk meer kans op uitzaaiingen en daardoor een veel kleinere overlevingskans.
Cancer drugs make tumors more aggressive and deadly
When natural health advocates warn against mainstream medicine's arsenal of weapons used to fight cancer, including chemotherapy and radiation, their concerns often revolve around how these therapies can weaken and damage a person's body in numerous ways. But scientists are finding other reasons to question some of these therapies. It turns out that while chemotherapies may kill or shrink tumors in the short term, they may actually be causing malignancies to grow more deadly in the long term.
Now comes news that a little-explored specific cell type, the pericyte, found in what is called the microenvironment of a cancerous tumor actually may halt cancer progression and metastasis. And by destroying these cells, some anti-cancer therapies may inadvertently be making cancer more aggressive as well as likely to spread and
kill.
A study just published in the journal Cancer Cell concludes that anti-angiogenic therapies (which shrink cancer by cutting off tumors' blood supply) may be killing the body's natural defense against cancer by destroying pericyte cells that likely serve as important gatekeepers against cancer progression and metastasis. Pericytes cover blood vessels and support their growth.
For the new research, Raghu Kalluri, MD, PhD, Chief of the Division of Matrix Biology at Beth Israel Deaconess Medical Center (BIDMC) and Professor of Medicine at Harvard Medical School (HMS), investigated whether targeting pericytes could inhibit tumor growth in the same way that other antiangiogenic cancer drugs do.
Dr. Kalluri and his research team worked with mice genetically engineered to support drug-induced depletion of pericytes in growing tumors. Next, they removed pericytes in implanted mouse breast cancer tumors, decreasing pericyte numbers by 60 percent.
Compared with control animals, there was a 30 percent decrease in the size of cancerous tumors over 25 days. But there was a serious catch to these results. Contrary to conventional mainsteam medical wisdom, the scientists discovered the number of secondary lung tumors in the engineered mice had increased threefold compared to the control mice, indicating that the tumors had metastasized.
How cancer drugs can spread cancer cells
"If you just looked at tumor growth, the results were good," Dr. Kalluri said in a press statement. "But when you looked at the whole picture, inhibiting tumor vessels was not controlling cancer progression. The cancer was, in fact, spreading. This suggested to us that without supportive pericytes, the vasculature inside the tumor was becoming weak and leaky -- even more so than it already is inside most tumors-- and this was reducing the flow of oxygen to the tumor."
That change, he explains, makes cancer cells more mobile, so they can travel through those leaky vessels to new locations. It also makes cancer cells behave more like stem cells, so they are better able to survive.
Because cancer therapies such as Imatinib, Sunitinib and others are known to decrease pericytes in tumors, the scientists next carried out the same experiments in mice with primary tumors. Only this time, they used the chemotherapy drugs Imatinib and Sunitinib instead of genetic programs to decrease pericyte numbers. Both Imatinib and Sunitinib caused 70 percent pericyte depletion -- and they also increased metastasis
threefold.
In order to see if their findings are relevant to human patients, the research team examined 130 breast cancer tumor samples of varying cancer stages and tumor sizes and compared pericyte levels with prognoses. The result? The samples with low numbers of pericytes in tumor vasculature correlated with the most deeply invasive cancers, distant metastasis and five to ten year survival rates less than 20 percent.
"These results are quite provocative and will influence clinical programs designed to target tumor angiogenesis," Ronald A. DePinho, president of the University of Texas MD Anderson Cancer Center, said in a press statement. "These impressive studies will inform and refine potential therapeutic approaches for many
cancers."
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artikel.
(Januari 2012)
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