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Old 03-22-2018, 02:20 AM   #1
Lani
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Three-in-one molecule shows promise in her2+ bc

Three-in-one molecule shows promise in helping certain breast cancer patients
A newly designed three-part molecule could be the one answer patients with a certain form of breast cancer are looking for, scientists report.

MEDICAL COLLEGE OF GEORGIA AT AUGUSTA UNIVERSITY


CREDIT: PHIL JONES, SENIOR PHOTOGRAPHER, AUGUSTA UNIVERSITY

AUGUSTA, Ga. (Mar. 19, 2018) - A newly designed three-part molecule could be the one answer patients with a certain form of breast cancer are looking for, scientists report.

This chimera, created by a team at the Georgia Cancer Center, has the ability to simultaneously decrease the expression of three growth factors that are over-expressed in some cancers.

The growth factors are human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), and epidermal growth factor receptor (EGFR). The new chimera interferes with HER2 and HER3 signaling and ultimately leads to cancer cell death, as shown in the group's recent publication in Molecular Therapy: Nucleic Acids.

"When HER2 is expressed in a cell, you'll usually find high expression of HER3, too," said Dr. Hongyan Liu, bioengineer at the Georgia Cancer Center at Augusta University and the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia at Augusta University.

Extensive studies have found that 20% to 30% of breast cancers are characterized by over-expression of HER2, which makes the cancer cells grow and divide faster, leading to a cancer that's more aggressive and more likely to be resistant to the standard of care. Patients with this type of breast cancer tend to have a poorer prognosis.

"As a bioengineer, I am developing the materials for cancer-targeted treatment," Liu said. "I have experience building multifunctional chimeras to target different types of genes associated with cancer cells."

Liu and her team created their molecule to target HER family receptors EGFR, HER2, and HER3 all at once, since it is well-known that another HER family member can compensate for one that is blocked by a drug having a single target.

Each component of this tripartite molecule has potent anti-tumor activity. The molecule was designed such that the EGFR-targeting component is sandwiched between the HER2- and HER3-targeting components in what is known as a HER2 aptamer-EGFR siRNA-HER3 aptamer chimera. This construction enables the EGFR component to reach its target within HER2- and HER3-expressing cells. Compared to individual components, the chimera is large enough to avoid renal depletion, resulting in a prolonged circulation time and increased efficiency.

The newly crafted molecule is non-toxic, simple to produce, and cost-effective compared to the production of alternate treatment strategies, such as antibodies and small molecule inhibitors.

Liu's ongoing studies are testing the ability of the three-in-one chimera to treat breast cancers that are resistant to Herceptin, a drug that targets HER2. This work is being done in collaboration with Dr. Hasan Korkaya, assistant professor, Biochemistry and Molecular Biology at the Medical College of Georgia, who has developed drug-resistant cell lines, and with breast cancer clinicians.

"We need to prove that this molecule will work on Herceptin-resistant breast cancer patients," Liu said.

Since other cancers, such as lung and head and neck, proliferate due to HER family over-expression, Liu anticipates that the chimera's utility will not be limited to breast cancers alone.

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Old 03-22-2018, 06:49 AM   #2
jra40
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Re: Three-in-one molecule shows promise in her2+ bc

Very interesting - thank you for posting Lani!
__________________
11/17/10 - Diagnosed with 4.5cm tumor in right breast, IDC, Stage 2, Nuclear grade 2, ER+ PR+ HER2+
12/13/10 - Lymph node biopsy - negative
12/28/10 - Started neo-adjuvant treatment along with clinical trial with 4 rounds of AC chemo every 3 weeks
3/15/11 - Began weekly Taxol/Herceptin infusions along with 750mg of Tykerb taken by mouth daily
6/28/11 - Finished last cycle of Taxol
7/27/11 - Breast MRI shows tumor has dissolved, remarkable reaction to chemo
8/31/11 - Lumpectomy, Sentinel Node biopsy. Node negative, clear margins, 7mm of cancer left over from chemo.
10/05/11 - Started radiation, 5 days a week for 7 weeks.
11/8/11 - Finished radiation
3/21/12 - Last Herceptin!
3/26/12 - Port removed!
Tamoxifen for 5 years
8/4/15 - Hysterectomy & bilateral salpingo-oophorectomy. Due to large fibroids. No cancer!
8/8/15 - Started Arimidex
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Old 03-22-2018, 10:28 PM   #3
Kim in CA
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Re: Three-in-one molecule shows promise in her2+ bc

Love the part that says: “The newly crafted molecule is non toxic, simple to produce, and cost-effective”!

Thanks for posting Lani, this one sounds so promising!
__________________
Diag. Feb 1997 4.5cm IDC <10%ER+, PR-. 5 out of 36 nodes +. Mastectomy followed by 3 rounds Adriamycin/Cytoxin.


5/1997 Hi Dose Chemo w/ Stem cell rescue. Spent 4 weeks in isolation ward. Then 6 weeks radiation.

9/2001 widespread mets to liver. 8 mos Taxotere/Herceptin brought me almost to NED. Stop Taxotere & add Femara .

11/2002 liver resection to remove spot that turned out to be necrosis. Officially NED!

7/2003 Tumor markers rising add Xeloda Disastrous reaction, 8 days hospital, but tumor markers came back to normal!

June -Dec 2004 UW Vaccine Trial.

7/2005 MRI single 11mm brain met
8/2005 Gamma Knife.

Brain MRI @3 months NED!

2006-2011 brain/body still NED

8/04/11 Taking Herceptin break, will monitor with tumor markers.

6/20/12 Tumor markers begin to rise. CA15-3 is 31.3 and Her2 Serum is at 17.1 Decide to repeat in one month.

7/23/12 CA15-3 now 49.3
Her2 Serum 26.8

8/6/12 Back on Herceptin
CA15-3 now 76
Her2 Serum now 49

11/7/12 Add weekly Taxotere for 4 cycles

2/2013 Stopped Taxotere added Perjeta. MRI shows approx. 50% reduction liver mets. CA15-3 still elevated @ 55. Will continue on just Herceptin & Perjeta.

November 2014 Continuing on Herceptin, Perjeta, and
Femara indefinitely. Guess I'm NED again, but watching those tumor markers carefully!

Dec. 2015 PET scan reveals mass in perirectal area of abdomen.biopsy confirms. Still Her2+, but no longer ER+. Bye bye Femara

Jan 2016 Begin Kadcyla

March 2016 PET scan shows tumor now barely visible, still NED everywhere else.
2016/2017 continue Kadcyla

November 2017 brain MRI reveals small focus of T2 hyperintensity with possible 4mm enhancing nodule. Short term follow up MRI suggested. Stay tuned...
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Old 03-23-2018, 08:23 AM   #4
Donna H
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Re: Three-in-one molecule shows promise in her2+ bc

So glad people continue to work on new treatments. This one sounds promising!
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