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Nathan Goodyear

Abstract GS2-06: Phase Ib/II study evaluating safety and efficacy of pembrolizumab and ... - 0 views

cancerres.aacrjournals.org/...GS2-06

PD-L1 breast cancer keytruda herceptin

shared by Nathan Goodyear on 25 May 21 - No Cached
  • Nathan Goodyear on 25 May 21
     
    The addition of keytruda to herceptin in herceptin resistant breast cancer shown to b safe and effective in small pilot trial; only abstract available here.
Nathan Goodyear

Interleukin‐2 enhances the natural killer cell response to Herceptin‐coated H... - 1 views

onlinelibrary.wiley.com/...%3AAID-IMMU3016%3E3.0.CO%3B2-J

IL-2 breast cancer cancer NK cells HER-2 immunotherapy

shared by Nathan Goodyear on 18 Jun 18 - No Cached
  • administration of low‐dose IL‐2 results in expansion of a CD3– / CD56+ NK cell population in patients with advanced cancer
  • approximately 20 % will overexpress theHer2 / neu proto‐oncogene
  • In breast cancer, Her2 / neu overexpression is associated with a worse histologicalgrade, decreased relapse‐free and overall survival periods, and altered sensitivity to chemotherapeutic regimens
  • ...17 more annotations...
  • NK cells are large granular lymphocytes that comprise approximately 10 % of circulating lymphocytes
  • all human NK cells express the CD56 antigen
  • treatment with various concentrations of IL‐2 in vivo may induce distinct functions within the NK cell compartment and, therefore, may have profound effects on NK cell‐mediated cytotoxicity
  • CD56bright
  • CD56dim
  • We show here that ADCC conducted by NK cells in vitro is enhanced by IL‐2 activation and is critically dependent on interactions between FcγRIII on NK cells and Herceptin‐coated tumor targets
  • administration of low‐dose IL‐2 to patients results in the marked expansion of a CD56+ population of immune effectors with the ability to lyse antibody‐coated cancer targets
  • NK cells represented only 7 % of lymphocytes prior to therapy but comprised over 50 % of the population after 10 weeks of low‐dose IL‐2
  • These data suggest that the enhanced ADCC seen following the expansion of NK cells with low‐dose IL‐2 is likely due to an increase in the overall number of NK cells
  • co‐administration of IL‐2 with rhu4D5 mAb will enhance activation of NK cell effector functions
  • Stimulation of NK cells with IL‐2 resulted in a significant increase in the lysis of rhu4D5‐coated targets
  • We have shown that costimulation with IL‐2 plus rhu4D5 results in significant production of IFN‐γ by NK cells with concomitant up‐regulation of cell‐surface activation and adhesion molecules
  • It has been previously demonstrated that continuous low‐dose IL‐2 can expand a CD56+ lymphocyte population, and we have now shown that this cell population is a potent mediator of ADCC against rhu4D5 mAb‐coated Her2 / neu+ targets
  • These results suggest that administration of low‐dose IL‐2 can be used to expand NK cell numbers, while higher doses may be used to enhance their cytolytic capacity in the setting of mAb therapy
  • we have demonstrated that NK cell lysis of Her2 / neu+ breast cancer cell lines in the presence of rhu4D5 mAb is markedly enhanced following stimulation with IL‐2
  • we have presented evidence that administration of low‐dose IL‐2 in vivo results in the expansion of a potent NK cell effector population
  • Our experiments suggest that NK cells costimulated with IL‐2 and immobilized IgG can secrete potent immunomodulatory cytokines which may serve to potentiate the anti‐tumor immune response.
  • Nathan Goodyear on 18 Jun 18
     
    low dose IL-2 found to expand NK levels in conjuction in with herceptin in HER-2 positive breast cancer cell lines.
Nathan Goodyear

A phase II trial of trastuzumab in combination with low-dose interleukin-2 (IL-2) in pa... - 0 views

link.springer.com/...s10549-008-0251-7

herceptin IL-2 breast cancer cancer trastuzumab NK cells

shared by Nathan Goodyear on 18 Jun 18 - No Cached
  • Nathan Goodyear on 18 Jun 18
     
    phase II study of herceptin and IL-2 found no benefit of NK cell expansion
Nathan Goodyear

Trastuzumab and Interleukin-2 in HER2-positive Metastatic Breast Cancer | Clinical Canc... - 0 views

clincancerres.aacrjournals.org/...2440

breast cancer cancer herceptin IL-2 immunotherapy trastuzumab

shared by Nathan Goodyear on 18 Jun 18 - No Cached
  • Nathan Goodyear on 18 Jun 18
     
    Herceptin and IL-2 increase NK cell expansion when used in conjunction.  The IL-2 was the low dose protocol for 7 weeks.
Nathan Goodyear

Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer t... - 0 views

www.sciencedirect.com/...S0960977617300103

HER-2 breast cancer cancer herceptin Perjeta

shared by Nathan Goodyear on 06 Aug 18 - No Cached
  • 15%–20%
  • key mediator of cell growth, differentiation, and survival
  • of higher histological grade and are more likely to invade axillary lymph nodes
  • ...15 more annotations...
  • shortened survival and an increased risk of disease recurrence and metastasis
  • Currently, four HER2-directed agents are approved for the treatment of patients with HER2+ breast cancer: trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1)
  • biosimilars
  • trastuzumab may provide greater benefit when administered concurrently with chemotherapy rather than after, and this has become the standard approach
  • concurrent use of anthracyclines (ie, doxorubicin or epirubicin) and trastuzumab is not recommended because of an increased risk for cardiac toxicity
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      avoid herceptin in conjuction with antracyclines i.e. doxorubicin
  • Sequential doxorubicin plus cyclophosphamide followed by concomitant paclitaxel or docetaxel and trastuzumab is recommended for most patients
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      top recommended regimen combination
  • Guidelines also recommend trastuzumab in combination with paclitaxel, docetaxel and carboplatin, or docetaxel and cyclophosphamide, particularly for patients with increased risk for cardiac toxicity or those with small (≤1 cm), node-negative HER2+ tumors
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      good alternative in patients with increased risk of cardiac toxicity.
  • guidelines recommend up to 1 year of adjuvant trastuzumab
  • Neoadjuvant chemotherapy with trastuzumab is associated with higher rates of pathologic complete response (pCR) than chemotherapy alone or in combination with lapatinib
  • the combination of trastuzumab, lapatinib, and chemotherapy is not recommended because it failed to demonstrate noninferiority versus trastuzumab and chemotherapy in the adjuvant setting
  • recommend the combination of trastuzumab, pertuzumab, and chemotherapy as neoadjuvant treatment for patients with locally advanced HER2+ breast cancer and for some patients (node-positive or tumor ≥2 cm) with early-stage disease
  • neoadjuvant chemotherapy in combination with pertuzumab and trastuzumab reduced the risk of progression or death by 31% and recurrence or death by 40% versus trastuzumab alone
  • Concurrent chemotherapy and HER2-directed therapy improves survival outcomes over chemotherapy alon
  • dual inhibition of HER2 with trastuzumab and pertuzumab in combination with paclitaxel reduced the risk of death or progression by approximately 40% compared with concurrent trastuzumab and paclitaxel
  • the combination of trastuzumab, pertuzumab, and taxane chemotherapy is the preferred first-line regimen
  • Nathan Goodyear on 06 Aug 18
     
    HER-2 + breast cancer = appx 15-20% of all breast cancers and is a marker of worse prognosis and an indication for targeted immunotherapy blockade.
Nathan Goodyear

Adaptive changes result in activation of alternate signaling pathways and acquisition o... - 0 views

www.ncbi.nlm.nih.gov/...PMC3131492

ER alpha cancer aromatase inhibitor breast ER-alpha HER-2

shared by Nathan Goodyear on 14 Sep 20 - No Cached
  • Nathan Goodyear on 14 Sep 20
     
    Interesting cross-talk between EGF and ER. Inhibition of EGFR increases ER-alpha. Herceptin is a negative signal on ER expression.
Nathan Goodyear

The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer... - 0 views

www.ncbi.nlm.nih.gov/...PMC3162976

curcumin HER-2 breast cancer NF-KappaB

shared by Nathan Goodyear on 19 Jan 12 - No Cached
  • Nathan Goodyear on 19 Jan 12
     
    Curcumin downregulates HER-2 oncoprotein in breast cancer in vitro and in vivo.  IN this study, the combination of taxol and curcumin was comparable to that of taxol and perceptin.
Nathan Goodyear

Oleic acid, the main monounsaturated fatty acid of olive oil, suppresses Her-... - 0 views

annonc.oxfordjournals.org/...359.abstract

breast cancer oleic acid extra virgin olive oil

shared by Nathan Goodyear on 30 Nov 10 - No Cached
  • Nathan Goodyear on 30 Nov 10
     
    Olive Oil helps in Breast Cancer therapy
Nathan Goodyear

The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer... - 0 views

www.hindawi.com/...486568

EGFR HER-2 MAPK PI3k_Akt oncogene curcumin breast cancer

shared by Nathan Goodyear on 14 May 21 - No Cached
  • Nathan Goodyear on 14 May 21
     
    Curcumin found to decrease HER-2, EGFR and effectively decrease the PI3k/Akt and MAPK signaling pathways.
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