New Posts New Posts RSS Feed - Targeting PI3K and JAK2/STAT5 Pathways
  FAQ FAQ  Forum Search   Events   Register Register  Login Login

Targeting PI3K and JAK2/STAT5 Pathways

 Post Reply Post Reply
Author
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 13509
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Topic: Targeting PI3K and JAK2/STAT5 Pathways
    Posted: Dec 13 2012 at 8:22am

Targeting PI3K and JAK2/STAT5 Pathways

One of the most frustrating truths aboutcancer 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 cancer biology 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 cancer cells in order to anticipate resistance mechanisms 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 tumor development 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 breast tumors 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." 
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
dmwolf View Drop Down
Senior Member
Senior Member
Avatar

Joined: Jan 22 2009
Location: Berkeley, CA
Status: Offline
Points: 3619
Post Options Post Options   Thanks (0) Thanks(0)   Quote dmwolf Quote  Post ReplyReply Direct Link To This Post Posted: Dec 13 2012 at 4:03pm
In part this shows the dangers of targeted cancer treatment.  If you hit a pathway with a lot of feedback loops in the wrong way, it can actually make the cancer more aggressive.  This is where the focus is going these days, figuring out how to combine targeted treatments so that aggressive phenotypes are disabled along multiple fronts simultaneously.  The hope is that eventually treating cancer will be like treating HIV - several drugs combined to prevent even a very mutation prone cell population from proliferating and rapidly evolving around the treatment.  Making metastatic breast cancer a chronic condition, like hiv has become.

DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.
Back to Top
 Post Reply Post Reply
  Share Topic   

Forum Jump Forum Permissions View Drop Down

Forum Software by Web Wiz Forums® version 12.01
Copyright ©2001-2018 Web Wiz Ltd.