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01-12-2011, 04:45 AM
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#1
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Senior Member
Join Date: Feb 2009
Posts: 1,526
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Her 2 and Her 3 signalling and Dr M Moasser
Hi everyone
I have been reading the research from Dr Moasser about the relationship between her 2 and her 3 and the possible explanation of why herceptin alone may not be enough to contain bc.
He believes that it will be possible to eradicate advanced bc if we can get this combination right and 3 days (yes days) of no signalling kills the cells!!
Wondered if anyone had more info or knew if there were any trials yet?
He seems to be advocating short high doses of lapatinib with rapamycin, a drug I understand is used to stop rejection of transplanted organs.
Hope I have got the essence of this correct. If not maybe Lani, Steph or someone will chime in.
Ellie
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01-12-2011, 10:12 AM
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#2
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Guest
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Re: Her 2 and Her 3 signalling and Dr M Moasser
Please Ellie, could you give a link?
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01-12-2011, 11:10 AM
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#3
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Guest
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Re: Her 2 and Her 3 signalling and Dr M Moasser
He has had (and might still have) small trials at UCSF of high dose intermittent Tykerb. I don't know about with the other drug. You could check the UCSF trial website for further information.
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01-12-2011, 11:35 AM
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#4
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Guest
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Re: Her 2 and Her 3 signalling and Dr M Moasser
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01-12-2011, 12:15 PM
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#5
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Senior Member
Join Date: Feb 2009
Posts: 1,526
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Re: Her 2 and Her 3 signalling and Dr M Moasser
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01-12-2011, 01:42 PM
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#6
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Guest
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Re: Her 2 and Her 3 signalling and Dr M Moasser
Thank you Ellie, its called "Research Grants Awarded", does it mean that Doctor Moasser has become this grant?
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01-13-2011, 05:11 AM
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#7
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Guest
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Hurray
A drug that targets HER2, called Tykerb, now is being used to test this new dosing strategy. In the clinical trial, women with advanced breast cancer are being treated with large, intermittent dosages of the drug instead of with daily, lower-dosage treatment. The larger dosage should more effectively kill tumor cells, Moasser, says. Breaks in treatment are intended to limit side effects.
The Phase 1 clinical trial is open to women with HER2-positive breast cancers that continue to grow after prior treatment with standard therapies.
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01-13-2011, 05:37 AM
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#8
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Guest
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Re: Her 2 and Her 3 signalling and Dr M Moasser
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01-13-2011, 08:30 AM
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#9
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Re: Her 2 and Her 3 signalling and Dr M Moasser
for those confused by unregistered's post--lapatinib and tykerb are one and the same drug.
Hope this helps!
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01-13-2011, 09:30 AM
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#10
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Senior Member
Join Date: Feb 2009
Posts: 1,526
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Re: Her 2 and Her 3 signalling and Dr M Moasser
Thanks Lani
I feel really frustrated that we POSSIBLY have the cure or at least a long term management strategy YET we still seem as far away as ever.So far it really seems hit and miss, with more toxic chemos which I believe equips the cancer cells to create greater survival strategies! Is it not time now medicine has reached this consensus that they get together and develop trials that either support or disprove this hypothesis?
One question I have, does bone marrow sampling always indicate the prescence of tumour cells?
Sorry to go on!!
Ellie
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01-13-2011, 01:28 PM
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#11
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Senior Member
Join Date: Sep 2005
Location: Central Coast, CA
Posts: 3,207
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Re: Her 2 and Her 3 signalling and Dr M Moasser
Lani,
you are right on target, so to speak!
__________________
Chris in Scotts Valley
June 2002 extensive hi grade DCIS (pre-cancer-stage 0, clean sentinal node) Mastectomy/implant - no chemo, rads. "cured?"
9/2004 Diag: Stage IV extensive liver mets (!) ER/PR- Her2+++
10/04-3/05 Weekly Taxol/Carboplatin/Herceptin , complete response!
04/05 - 4/07 Herception every 3 wks, Continue NED
04/07 - recurrence to liver - 2 spots, starting tykerb/avastin trial
06/07 8/07 10/07 Scans show stable, continue on Tykerb/Avastin
01/08 Progression in liver
02/08 Begin (TDM1) trial
08/08 NED! It's Working! Continue on TDM1
02/09 Continue NED
02/10 Continue NED. 5/10 9/10 Scans NED 10/10 Scans NED
12/10 Scans not clear....4/11 Scans suggest progression 6/11 progression confirmed in liver
07/11 - 11/11 Herceptin/Xeloda -not working:(
12/11 Begin MM302 Phase I trial - bust:(
03/12 3rd times the charm? AKT trial
5/12 Scan shows reduction! 7/12 More reduction!!!!
8/12 Whoops...progression...trying for Perjeta/Herceptin (plus some more nasty chemo!)
9/12 Start Perjeta/Herceptin, chemo on hold due to infection/wound in leg, added on cycle 2 &3
11/12 Poops! progression in liver, Stop Perjeta/Taxo/Herc
11/12 Navelbine/Herce[ptin - try for a 3 cycles, no go.
2/13 Gemzar/Carbo/Herceptin - no go.
3/13 TACE procedure
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01-13-2011, 04:05 PM
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#12
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Re: Her 2 and Her 3 signalling and Dr M Moasser
No Ellie. It is a better predictor of minimal residual disease, future recurrence than CTCs and when her2+ the bone marrow cells (DTCs) are much better able to predict recurrence than when her2-. It seems her2+ patients rarely have her2- DTCs in their bone marrow, but her2-s may have her2+ cells, especially after they have been treated with antihormonals or chemos (ie, their cancer tries to switch to increase her signalling in order to survive the onslaught of chemos)
Remember these cells may be very slowly dividing and more difficult to eradicate with chemo therefore and may represent the cancer stem cells responsible for recurrences, if you adhere to the stem cell theory of breast cancer, which i do.
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01-13-2011, 04:11 PM
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#13
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Guest
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Re: Her 2 and Her 3 signalling and Dr M Moasser
Lani, could you answer please:
so,
1) Blockade of her3 is not a cure?
2) Can any researcher block her3 for now?
3) What do you think about M. Moasser's study with extremaly dosage of lapatinib?
Thank you
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01-13-2011, 07:22 PM
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#14
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Re: Her 2 and Her 3 signalling and Dr M Moasser
blocking her2 is not necessarily a cure for all her2+ breast cancers for the Ireasons I listed above and others, such as upregulation of EGFR, IGFR1 etc.
Blocking her2 and her3 or blocking egfr, her2 and her3 may be a cure for a subgroup of her2+ breast cancers especially done so quickly that the tumor does not have time to find another signalling pathway to get around the blockade.
THere are drugs which block her3 which are used by researchers and in some clinical trials. Dr Ulrich, who got the AACR lifetime achievement award for herceptin (he did the work at Genentech) believes blocking her3 will be the most beneficial and effective way to work towards curing her2+ breast cancer.
Am not quite sure what you mean re Dr. Moasser's work, but if you are referring to giving the doses more intermittently rather than continuously to decrease the side effects, I would have to reread any articles to form an opinion. Obviously it would be nice for patient to go for longer periods without diarrhea!!
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01-13-2011, 07:30 PM
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#15
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Re: Her 2 and Her 3 signalling and Dr M Moasser
here is a quick bibliography of Dr Moasser's articles on the topic (and closely related ones):
The role of HER3, the unpretentious member of the HER family, in cancer biology and cancer therapeutics.
Amin DN, Campbell MR, Moasser MM.
Semin Cell Dev Biol. 2010 Dec;21(9):944-50. Epub 2010 Sep 9.
PMID: 20816829 [PubMed - in process]
Related citations
3.
Resiliency and vulnerability in the HER2-HER3 tumorigenic driver.
Amin DN, Sergina N, Ahuja D, McMahon M, Blair JA, Wang D, Hann B, Koch KM, Shokat KM, Moasser MM.
Sci Transl Med. 2010 Jan 27;2(16):16ra7.
PMID: 20371474 [PubMed - indexed for MEDLINE]
Related citations
4.
HER3 comes of age: new insights into its functions and role in signaling, tumor biology, and cancer therapy.
Campbell MR, Amin D, Moasser MM.
Clin Cancer Res. 2010 Mar 1;16(5):1373-83. Epub 2010 Feb 23.
PMID: 20179223 [PubMed - indexed for MEDLINE]
Related citations
5.
A phase I study of a 2-day lapatinib chemosensitization pulse preceding nanoparticle albumin-bound Paclitaxel for advanced solid malignancies.
Chien AJ, Illi JA, Ko AH, Korn WM, Fong L, Chen LM, Kashani-Sabet M, Ryan CJ, Rosenberg JE, Dubey S, Small EJ, Jahan TM, Hylton NM, Yeh BM, Huang Y, Koch KM, Moasser MM.
Clin Cancer Res. 2009 Sep 1;15(17):5569-75. Epub 2009 Aug 25.
PMID: 19706807 [PubMed - indexed for MEDLINE]Free Article
Related citations
6.
MRI methods for evaluating the effects of tyrosine kinase inhibitor administration used to enhance chemotherapy efficiency in a breast tumor xenograft model.
Aliu SO, Wilmes LJ, Moasser MM, Hann BC, Li KL, Wang D, Hylton NM.
J Magn Reson Imaging. 2009 May;29(5):1071-9.
PMID: 19388114 [PubMed - indexed for MEDLINE]
Related citations
9.
A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer.
Dickler MN, Rugo HS, Eberle CA, Brogi E, Caravelli JF, Panageas KS, Boyd J, Yeh B, Lake DE, Dang CT, Gilewski TA, Bromberg JF, Seidman AD, D'Andrea GM, Moasser MM, Melisko M, Park JW, Dancey J, Norton L, Hudis CA.
Clin Cancer Res. 2008 Dec 1;14(23):7878-83.
PMID: 19047117 [PubMed - indexed for MEDLINE]Free PMC ArticleFree text
Related citations
10.
HER-2-directed, small-molecule antagonists.
Arkin M, Moasser MM.
Curr Opin Investig Drugs. 2008 Dec;9(12):1264-76. Review.
PMID: 19037833 [PubMed - indexed for MEDLINE]
Related citations
11.
A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition.
Torbett NE, Luna-Moran A, Knight ZA, Houk A, Moasser M, Weiss W, Shokat KM, Stokoe D.
Biochem J. 2008 Oct 1;415(1):97-110.
PMID: 18498248 [PubMed - indexed for MEDLINE]Free Article
Related citations
13.
The epidermal growth factor receptor family: biology driving targeted therapeutics.
Wieduwilt MJ, Moasser MM.
Cell Mol Life Sci. 2008 May;65(10):1566-84. Review.
PMID: 18259690 [PubMed - indexed for MEDLINE]
Related citations
14.
The HER family and cancer: emerging molecular mechanisms and therapeutic targets.
Sergina NV, Moasser MM.
Trends Mol Med. 2007 Dec;13(12):527-34. Epub 2007 Nov 5. Review.
PMID: 17981505 [PubMed - indexed for MEDLINE]
Related citations
15.
Improved tumor vascular function following high-dose epidermal growth factor receptor tyrosine kinase inhibitor therapy.
Moasser MM, Wilmes LJ, Wong CH, Aliu S, Li KL, Wang D, Hom YK, Hann B, Hylton NM.
J Magn Reson Imaging. 2007 Dec;26(6):1618-25.
PMID: 17968965 [PubMed - indexed for MEDLINE]
Related citations
17.
Targeting HER proteins in cancer therapy and the role of the non-target HER3.
Hsieh AC, Moasser MM.
Br J Cancer. 2007 Aug 20;97(4):453-7. Epub 2007 Jul 31. Review.
PMID: 17667926 [PubMed - indexed for MEDLINE]Free PMC ArticleFree text
Related citations
18.
Targeting the function of the HER2 oncogene in human cancer therapeutics.
Moasser MM.
Oncogene. 2007 Oct 11;26(46):6577-92. Epub 2007 May 7. Review.
PMID: 17486079 [PubMed - indexed for MEDLINE]
Related citations
19.
The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis.
Moasser MM.
Oncogene. 2007 Oct 4;26(45):6469-87. Epub 2007 Apr 30. Review.
PMID: 17471238 [PubMed - indexed for MEDLINE]
Related citations
20.
Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3.
Sergina NV, Rausch M, Wang D, Blair J, Hann B, Shokat KM, Moasser MM.
Nature. 2007 Jan 25;445(7126):437-41. Epub 2007 Jan 7.
PMID: 17206155 [PubMed - indexed for MEDLINE]
Related citations
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01-14-2011, 05:22 AM
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#16
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Senior Member
Join Date: Feb 2009
Posts: 1,526
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Re: Her 2 and Her 3 signalling and Dr M Moasser
Lani-just wanted to say many thanks for keeping us so well informed.
What I seem to have gathered so far is that it is thought that there are many sub-groups within her2 bc (let alone all the other types).At present we do not have sophisticated assessment tools for us to be able to determine all of these sub types and even less idea which combination of drugs will be effective (assuming that we have discovered enough drugs to treat all sub types!) The result seems to be pick and mix of chemos for advanced breast cancer (and some early stage).
I remember a famous onc from MSKCC talking about needing to use good scientific analysis with a mathematical model to determine individual treatment regimes. Why are we still so far away from this???
Ellie
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01-14-2011, 07:19 AM
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#17
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Senior Member
Join Date: Aug 2010
Location: New York, New York
Posts: 1,580
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Re: Her 2 and Her 3 signalling and Dr M Moasser
HER3 is a new one for me...what exactly is it? What is its relationship to HER2? Thanks,
__________________
World Trade Center Survivor (56th Floor/North Tower): 14 years and still just like yesterday.
Graves Disease, became Euthyroid via Radioactive Iodine, June 2001.
Thyroid Eye Disease. 2003. Decompression surgery in 2009; eyelid lowering surgery in 2010.
Diagnosed: June 2010, liver mets. ER-/PR+10%; HER2+++.
July 2010: Begin Taxol/Herceptin. Eliminate sugar from diet. No surgery or radiation.
January 2011: NED
April 2011: Progression in liver only. Other previous affected areas eradicated. Stop Taxol/Herceptin after 32 infusions.
May 2011: Brain MRI: clear.
May 2011: Begin Tykerb daily, Xeloda twice per day for one week on, one week off, and Herceptin.
November 2011: Progression in liver. All other tumors remain eradicated.
December 2011: BEGIN TRIAL #09-093 Taxol, MCC-DM1 (T-DM1), Perjeta.
Trial requires scans every six weeks, bloodwork and infusions weekly.
Brain MRI: clear.
January 2012: NED. Liver mets, good riddance!
March 2012: NED. Developed SMA (rare blood clot) in intestinal artery and loss of sight in right eye due to optical nerve neuropathy. Resolved when Taxol removed this month.
Continue Protocol of T-DM1 weekly and Perjeta every 3 weeks.
May 2012: NED.
June 2012: Brain MRI: clear.
June-December 2012: NED.
December 2012: TRIAL CONCLUDED; ENTER TRIAL EXTENSION #09-037. CT, Brain MRI, bone scan: clear. NED.
January-March 2013: NED.
June 2013: Brain MRI: clear. CEA upticking; CT shows new met on liver.
July 3, 2013: DISASTER STRIKES during liver ablation: sloppy surgeon cuts intercostal artery and I bleed out, lose 3.5 liters of blood, have major hemothorax, and collapsed lung requiring emergency resuscitative thoracotomy, lung surgery, rib rearrangement and cutting deep connective tissue, transfusion. Ablation incomplete. This life-saving procedure would end up causing me unforgiving pain with every movement I make, permanently, otherwise known as forever.
July 26, 2013: Try Navelbine/Herceptin. Body too weak after surgery and transfusion. Fever. CEA: Normal.
August 16, 2016: second dose Navelbine/Herceptin; CEA: Normal. Will skip doses. Watching and waiting.
September 2013: NED, Herceptin only. CEA: Normal. Started Arimidex.
October-November 2013: NED. Herceptin and Arimidex. CEA, CA125, 15-3: Normal.
December 2013: Something brewing. PET lights up on little spot on liver; CEA upward trend, just outside normal. PET and triphasic liver scan confirm Little Met. Restart Perjeta with Herceptin, stay on Arimidex. Genomic sequencing completed for future treatments, if necessary.
January 2014: Ablate Little Met on the 6th. Happy New Year.
March 2014: Brain MRI: clear. PET/CT reveal liver mets return; new lung mets. This is not funny.
March 2014: BEGIN TRIAL #10-005 A(11)-Temsirolimus plus Neratinib.
April 2014: Genomic testing indicated they could work, they did not. Very strange drug combo for me, felt weird.
April 2014: Started Navelbine and Herceptin. Needed something tried and true, but had significant progression.
June 2014: Doxil and Herceptin.
July 2014: Progression. Got nothing out of it. Brain: NED.
July 2014: Add integrative medical hematologist-oncologist to my team. Begin supplements. These are tumor-busting, immune system boosters. Add glutathione, lysine and taurine IV infusions every three weeks.
July 2014: Begin Gemzar, Herceptin & Perjeta. Happy.
August 2014: ECHO perfect.
January 2015: Begin weekly Vitamin D Analog infusions. 25 mcg. via port.
February 2015: CT: stable.
April 2015: Gem working, but not 100%. Looking into immunotherapy. Finally, treatments for the 21st century!
April 2015: Penn Medicine. Dendritic cell immunotherapy.
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01-15-2011, 11:11 AM
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#18
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Re: Her 2 and Her 3 signalling and Dr M Moasser
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