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Scientist Profile

Mark Sliwkowski

Senior Staff Scientist, Research Oncology
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"One cannot adequately describe the excitement that permeates our company when we learn that one of our drugs helps critically ill patients."

I joined Genentech in 1991 as a senior scientist and have worked on a number of programs involving drugs directed against the human epidermal growth factor receptor family (also known as the HER or ErbB family). Gratifyingly, two of these drugs, Herceptin (Trastuzumab) and Tarceva (erlotinib) have received U.S. Food and Drug Administration approval.

In September 1998, Herceptin was approved in combination with paclitaxel for the first-line treatment of HER2-positive metastatic breast cancer. In November of 2006, Herceptin was approved by the FDA as part of a treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel, for the adjuvant treatment of patients with HER2-positive, node-positive breast cancer. In January 2008, Herceptin was approved by the FDA as a single agent for the adjuvant treatment of HER2-overexpressing node-negative (ER/PR-negative or with one high-risk feature) or node-positive breast cancer, following multi-modality anthracycline-based therapy. In April of 2004, it was announced that Tarceva extended the survival of patients with relapsed non-small cell lung cancer. Later that same year, FDA approved Tarceva for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.

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My Focus

The epidermal growth factor receptor network, also known as the HER or ErbB family, is frequently activated in a number of proliferative diseases including cancer.

Our lab focuses on studying various aspects of this receptor activation process including the biochemical nature of the receptor complexes, the activation of signal transduction pathways, and the resultant biological outcomes. These investigations have contributed to the development of a number of therapeutic approaches that target the receptor family such as Herceptin, pertuzumab, Tarceva, and a trastuzumab-DM1 conjugate. Working closely with the Oncology Diagnostics and Pathology Departments, our current effort deals primarily with identifying a molecular profile that may aid in selecting patients who may benefit from pertuzumab therapy. We are also actively investigating combination therapeutic approaches and exploring mechanisms of resistance.

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Publications & Recognition
  • Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
  • J Clin Oncol. 2010 Mar 1; 28(7): 1215-23
  • Makhija S, Amler LC, Glenn D, Ueland FR, Gold MA, Dizon DS, Paton V, Lin CY, Januario T, Ng K, Strauss A, Kelsey S, Sliwkowski MX, Matulonis U
  • View Abstract on PubMed
  • Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941
  • Cancer Cell 2009; 15: 429-40
  • Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D, Sliwkowski MX
  • View Abstract on PubMed
  • Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate
  • Cancer Res 2008; 68: 9280-90
  • Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, Blattler WA, Lambert JM, Chari RV, Lutz RJ, Wong WL, Jacobson FS, Koeppen H, Schwall RH, Kenkare-Mitra SR, Spencer SD, Sliwkowski MX
  • View Abstract on PubMed
 
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  • National Institutes of Health, National Heart, Lung and Blood Institute
  • Staff Fellow
  • 1982-1985
  • North Carolina State University, Department of Biochemistry
  • Ph.D
  • 1977-1981
  • University of Delaware, Department of Animal Science and Agricultural Biochemistry
  • B.S
  • 1972-1976
Publications & Recognition
  • Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
  • J Clin Oncol. 2010 Mar 1; 28(7): 1215-23
  • Makhija S, Amler LC, Glenn D, Ueland FR, Gold MA, Dizon DS, Paton V, Lin CY, Januario T, Ng K, Strauss A, Kelsey S, Sliwkowski MX, Matulonis U
  • View Abstract on PubMed
  • Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941
  • Cancer Cell 2009; 15: 429-40
  • Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D, Sliwkowski MX
  • View Abstract on PubMed
  • Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate
  • Cancer Res 2008; 68: 9280-90
  • Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, Blattler WA, Lambert JM, Chari RV, Lutz RJ, Wong WL, Jacobson FS, Koeppen H, Schwall RH, Kenkare-Mitra SR, Spencer SD, Sliwkowski MX
  • View Abstract on PubMed
  • Kinetic analysis of epidermal growth factor receptor somatic mutant proteins shows increased sensitivity to the epidermal growth factor receptor inhibitor, erlotinib
  • Cancer Res. 2006 Aug 15; 66(16): 8163-71
  • Carey KD, Garton AJ, Romero MS, Kahler J, Thomson S, Ross S, Park F, Haley JD, Gibson N, Sliwkowski MX
  • View Abstract on PubMed
  • Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab
  • Cancer Immunol Immunother. 2006 Jun; 55(6): 717-27
  • Adams C, Allison DE, Flagella K, Presta L, Clarke J, Dybdal N, McKeever K, Sliwkowski MX
  • View Abstract on PubMed
  • Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer
  • J Clin Oncol. 2005 Apr 10; 23(11): 2534-43
  • Agus DB, Gordon MS, Taylor C, Natale RB, Karlan B, Mendelson DS, Press MF, Allison DE, Sliwkowski MX, Lieberman G, Kelsey SM, Fyfe G
  • View Abstract on PubMed
  • Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex
  • Cancer Cell. 2004 Apr; 5(4): 317-28
  • Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX
  • View Abstract on PubMed
  • Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor
  • J Biol Chem 2002 Nov 29; 277(48): 46265-72
  • Stamos J, Sliwkowski MX, Eigenbrot C
  • View Abstract on PubMed
  • Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth
  • Cancer Cell 2002 Aug; 2(2): 127-37
  • Agus DB, Akita RW, Fox WD, Lewis GD, Higgins B, Pisacane PI, Lofgren JA, Tindell C, Evans DP, Maiese K, Scher HI, Sliwkowski MX
  • View Abstract on PubMed
  • Identification of a region within the ErbB2/HER2 intracellular domain that is necessary for ligand-independent association
  • J Biol Chem 2002 Aug 9; 277(32): 28468-73
  • Penuel E, Akita RW, Sliwkowski MX
  • View Abstract on PubMed
  • Growth regulation of human breast and ovarian tumor cells by heregulin: Evidence for the requirement of ErbB2 as a critical component in mediating heregulin responsiveness
  • Cancer Res 1996 Mar 15; 56(6): 1457-65
  • Lewis GD, Lofgren JA, McMurtrey AE, Nuijens A, Fendly BM, Bauer KD, Sliwkowski MX
  • View Abstract on PubMed
  • Untangling the ErbB signalling network
  • Nat Rev Mol Cell Biol 2001 Feb; 2(2): 127-37
  • Yarden Y, Sliwkowski MX
  • View Abstract on PubMed
  • A discrete three-amino acid segment (LVI) at the C-terminal end of kinase-impaired ErbB3 is required for transactivation of ErbB2
  • J Biol Chem 1999 Jan 8; 274(2): 859-66
  • Schaefer G, Akita RW, Sliwkowski MX
  • View Abstract on PubMed
  • Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin
  • J Biol Chem 1994 May 20; 269(20): 14661-5
  • Sliwkowski MX, Schaefer G, Akita RW, Lofgren JA, Fitzpatrick VD, Nuijens A, Fendly BM, Cerione RA, Vandlen RL, Carraway KL 3rd
  • View Abstract on PubMed
  • Identification of heregulin, a specific activator of p185erbB2
  • Science 1992 May 22; 256(5060): 1205-10
  • Holmes WE, Sliwkowski MX, Akita RW, Henzel WJ, Lee J, Park JW, Yansura D, Abadi N, Raab H, Lewis GD
  • View Abstract on PubMed
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Awards & Honors
  • Industry Scientist of the Year, Pharmaceutical Achievement Award - 2005
  • Triton Research & Development Award - 1989
  • Industrial Initiative for Science and Math Education Award - 1989
  • American Society of Biological Chemistry Travel Grant - 1985
  • Phi Lambda Upsilon Chemistry Honor Society - 1981
  • Gamma Delta Sigma Agricultural Honor Society - 1981
  • Outstanding Graduate Student Teaching Award - 1979
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Ellen Filvaroff, Senior Scientist and Alex Avardo, Receipent of Free Medicine From the Genentech® Access to Care Foundation, on the cover of Genentech's 2006 Annual Report.