There’s a lot of talk about the potential for a better way to treat disease with more accurate delivery of nanoparticle-based medicines to specific areas that need the treatment. For example, current treatments which shrink and eliminate cancer tumours also destroy healthy tissue and often have deleterious side effects while a nanoparticle-based treatment could seek out and eliminate the tumour only with few or no side effects. However, new research suggests that tumours may be more complex than previously understood.
From a Jan. 14, 2015 news item on Azonano,
Nanoparticle drugs–tiny containers packed with medicine and with the potential to be shipped straight to tumors–were thought to be a possible silver bullet against cancer. However new cancer drugs based on nanoparticles have not improved overall survival rates for cancer patients very much. Scientists at the University of North Carolina at Chapel Hill now think that failure may have less to do with the drugs and tumors than it does the tumor’s immediate surroundings.
The work, published in Clinical Cancer Research, merges relatively old and new ideas in cancer treatment, on one hand underscoring the importance of personalized medicine and on the other, reinforcing a relatively new idea that the tumor microenvironment might affect the delivery of drugs to tumors – a factor that may alter drug delivery from person to person, from cancer to cancer and even from tumor to tumor.
A Jan. 13, 2015 University of North Carolina news release (also on EurekAlert), which originated the news item, provides more details about the research,
“Tumors create bad neighborhoods,” said William Zamboni, the study’s senior author and an associate professor at the UNC Eshelman School of Pharmacy. “They spawn leaky, jumbled blood vessels that are like broken streets, blind alleys and busted sewers. There are vacant lots densely overgrown with collagen fibers. Immune-system cells patrolling the streets might be good guys turned bad, actually working for the tumor. And we’re trying to get a large truckload of medicine through all of that.”
In their work, Zamboni and colleagues from the UNC Lineberger Comprehensive Cancer Center and the UNC School of Medicine joined forces to see how much of the standard small-molecule cancer drug doxorubicin and its nanoparticle version, Doxil, actually made it into two varieties of triple-negative breast-cancer tumor models created by UNC’s Chuck Perou, the May Goldman Shaw Distinguished Professor of Molecular Oncology at the UNC School of Medicine and a professor at UNC Lineberger. Triple-negative breast cancer accounts for 10 to 17 percent of cases and has a poorer prognosis than other types of breast cancer.
At first, what they saw was no surprise: significantly more of the nanodrug Doxil made it into both triple-negative breast-cancer tumors compared with the standard small-molecule doxorubicin. “That’s nothing new,” Zamboni said. “We’ve seen that for twenty years.” They also saw the same amount of doxorubin in both tumors.
What did surprise them was that significantly more of the nanodrug Doxil – twice as much – was delivered to the C3-TAg triple-negative breast cancer tumor than to the T11 triple-negative breast cancer tumor.
“These tumors are subtypes of a subtype of one kind of cancer and are relatively closely related,” said Zamboni. “If the differences in delivering nanoagents to these two tumors are so significant, we can only imagine what the differences might be between breast cancer and lung cancer.”
Zamboni and his team suggest that better profiling of tumors and their microenvironments would allow doctors not only to better identify patients who would most benefit from nanoparticle-based cancer therapy, but also that clinicians may need to learn more about a patient’s tumor before prescribing treatment with one of the newer nanoparticle drugs.
This work gives the Israeli project I wrote about in my Jan. 7, 2015 post regarding a human clinical trial of nanobot delivery of a drug treatment (the world’s first) a new perspective. As a medical writer friend of mine (Susan Baxter) notes, these things are always more complicated than we think they’ll be and she adds tumours change over time.
Given how often we’ve discovered the human body is a complex, interwoven set of ecosystems, it’s perplexing that so much of the discussion around treatment is still reductionist, i.e., drug kill tumour.
Getting back to this current research, here’s a link to and a citation for the paper,
Effects of Tumor Microenvironment Heterogeneity on Nanoparticle Disposition and Efficacy in Breast Cancer Tumor Models by Gina Song, David B. Darr, Charlene M. Santos, Mark Ross, Alain Valdivia, Jamie L. Jordan, Bentley R. Midkiff, Stephanie Cohen, Nana Nikolaishvili-Feinberg, C. Ryan Miller, Teresa K. Tarrant, Arlin B. Rogers, Andrew C. Dudley, Charles M. Perou, and William C. Zamboni. CCR-14-0493 Clin Cancer Res December 1, 2014 20 6083 doi: 10.1158/1078-0432 Published Online First September 17, 2014
This paper is behind a paywall of sorts. I haven’t seen this particular designation before but in addition to purchasing a subscription or short term access, there’s an option called: “patientACCESS – Patients/Caregivers desiring access to articles.” I’m not sure if that’s fee-based or not.