To fight incurable metastatic breast cancer, resistance must be broken

December 10, 2012, Cell Press

One of the most frustrating truths about cancer is that even when a treatment works, it often doesn't work for long because cancer cells find ways to resist. However, researchers reporting studies done in mice in the December 11, 2012, issue of Cancer Cell, a Cell Press publication, may have a way to stay one step ahead in the case of aggressive metastatic breast cancer.

The findings emphasize the importance of basic for advancing treatments that are more effective and less toxic, the researchers say.

"We need to gain a better understanding of the wiring diagram of in order to anticipate and plan the right combination therapies," says Mohamed Bentires-Alj of the Friedrich Miescher Institute for Biomedical Research in Switzerland. "Moreover, we need to better understand how cancer progresses to metastases."

After all, the spreading of cancer through metastasis is responsible for most cancer-related deaths.

In the new study, Bentires-Alj and his colleagues examined cancer cell lines and primary breast tumors to see what happens when those cancers are treated with a new type of therapy that targets the so-called PI3K pathway.

"The PI3K pathway is frequently mutated and activated in several human cancers where it plays a key role in and maintenance as well as in resistance to therapy," Bentires-Alj says, which explains why clinical trials evaluating some 26 PI3K inhibitors are now underway.

While those inhibitors are promising, there is some bad news, as the new work shows. When triple-negative are hit with PI3K inhibitors, cancer cells begin to produce a chemical that ramps up a second cancer pathway (JAK2/STAT5)—one that encourages the cancer to spread.

Now for the good news: when the researchers treated mice with an aggressive form of breast cancer with drugs to block both PI3K and JAK2/STAT5 pathways, their tumors grew more slowly, spread less readily, and, ultimately, the animals lived longer.

If Bentires-Alj has his way, the findings in mice will lead to clinical trials in the patients who are most likely to benefit: those with particularly aggressive, triple-negative breast cancers.

"We are in the era of personalized medicine," he says. "We hope that this combination therapy will be tested in clinical trials and that the right patients will be selected for these studies."

Explore further: New breast cancer model of mutant PI3K recapitulates features of human breast cancer

More information: Britschgi et al.: "JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade, Providing a Rationale for Co-targeting these Pathways in Metastatic Breast Cancer." DOI: 10.1016/j.ccr.2012.10.023

Related Stories

New breast cancer model of mutant PI3K recapitulates features of human breast cancer

July 12, 2011
Scientists from the Friedrich Miescher Institute for Biomedical Research have shown that a mutation in the lipid kinase PI3K, which occurs in about 30% of human breast cancers, itself evokes different forms of breast cancer. ...

New point of attack for breast cancer with poor prognosis

March 5, 2012
(Medical Xpress) -- Scientists from the Friedrich Miescher Institute for Biomedical Research describe how the protein phosphatase SHP2 promotes breast cancer with poor prognosis. As they report in the latest issue of Nature ...

Scientists identify overactive genes in aggressive breast cancers

June 1, 2011
Scientists at Dana-Farber Cancer Institute have identified an overactive network of growth-spurring genes that drive stem-like breast cancer cells enriched in triple-negative breast tumors, a typically aggressive cancer that ...

Hedgehog pathway key in tamoxifen-resistant breast CA

November 6, 2012
(HealthDay)—Noncanonical Hedgehog (Hh) signaling is activated in tamoxifen-resistant tumors, and the phosphoinositide 3-kinase inhibitor/protein kinase B (PI3K/AKT) pathway plays a key role protecting Hh signaling molecules, ...

Diverse genetic alterations found in triple-negative breast cancers after neoadjuvant chemotherapy

December 7, 2012
Many different genetic alterations were detected in tumor cells left behind after patients with triple-negative breast cancer were treated with chemotherapy prior to surgery (neoadjuvant chemotherapy), according to data presented ...

Recommended for you

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

New immunotherapy approach boosts body's ability to destroy cancer cells

January 12, 2018
Few cancer treatments are generating more excitement these days than immunotherapy—drugs based on the principle that the immune system can be harnessed to detect and kill cancer cells, much in the same way that it goes ...

Cancer's gene-determined 'immune landscape' dictates progression of prostate tumors

January 12, 2018
The field of immunotherapy - the harnessing of patients' own immune systems to fend off cancer - is revolutionizing cancer treatment today. However, clinical trials often show marked improvements in only small subsets of ...

FDA approves first drug for tumors tied to breast cancer genes

January 12, 2018
(HealthDay)—The U.S. Food and Drug Administration on Friday approved the first drug aimed at treating metastatic breast cancers linked to the BRCA gene mutation.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.