Mark Sliwkowski

Distinguished Staff Scientist, Research Oncology

POSTDOC MENTOR

"One cannot adequately describe the excitement that permeates our company when we learn that one of our drugs helps critically ill patients."

• 22
  years at Genentech
• 23
  publications (2010-12)
• 4
  awards & honors

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.

• 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.

• Publications

  • Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiation

    Cancer Research, 2012, ISSN: 0008-5472

    Huang, Shyhmin; Li, Chunrong; Armstrong, Eric A.; Peet, Chimera R.; Saker, Jarob; Amler, Lukas C.; Sliwkowski, Mark X.; Harari, Paul M.

     View on PubMed

  • Pari passu dimers of dimers

    Proceedings of the National Academy of Sciences, 2012, ISSN: 0027-8424

    Sliwkowski, Mark;

     View on PubMed

  • Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates

    Nature Biotechnology, 2012, ISSN: 1087-0156

    Shen, Ben-Quan; Xu, Keyang; Liu, Luna; Raab, Helga; Bhakta, Sunil; Kenrick, Margaret; Parsons-Reponte, Kathryn L; Tien, Janet; Yu, Shang-Fan; Mai, Elaine; Li, Dongwei; Tibbitts, Jay; Baudys, Jakub; Saad, Ola M; Scales, Suzie J; McDonald, Paul J; Hass, Philip E; Eigenbrot, Charles; Nguyen, Trung; Solis, Willy A; Fuji, Reina N; Flagella, Kelly M; Patel, Darshana; Spencer, Susan D; Khawli, Leslie A; Ebens, Allen; Wong, Wai Lee; Vandlen, Richard; Kaur, Surinder; Sliwkowski, Mark X; Scheller, Richard H; Polakis, Paul; Junutula, Jagath R

     View on PubMed

  • Treatment of HER2-positive breast cancer: Current status and future perspectives

    Nature Reviews Clinical Oncology, 6 Jan 2012, v9(1), p16-32, ISSN: 1759-4774

    Arteaga, Carlos L.; Sliwkowski, Mark X.; Osborne, C. Kent; Perez, Edith A.; Puglisi, Fabio; Gianni, Luca

     View on PubMed

  • Effects of anti-VEGF on pharmacokinetics, biodistribution and tumor penetration of trastuzumab in a preclinical breast cancer model

    Molecular Cancer Therapeutics, 5 Jan 2012, ISSN: 1538-8514

    Cinthia V. Pastuskovas; Eduardo E. Mundo; Simon P. Williams; Tapan K. Nayak; Jason Ho; Sheila Ulufatu; Suzanna Clark; Sarajane Ross; Eric Cheng; Kathryn Parsons-Reponte; Gary Cain; Marjie Van Hoy; Nicholas Majidy; Sheila Bheddah; Josefa dela Cruz Chuh; Katherine R. Kozak; Nicholas Lewin-Koh; Peter Nauka; Daniela Bumbaca; Mark Sliwkowski; Jay Tibbitts; Frank-Peter Theil; Paul J. Fielder; Leslie A. Khawli; and C. Andrew Boswell

     View on PubMed

  • Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941

    Cancer Cell, 2011, ISSN: 1535-6108

    Junttila, Teemu T.; Akita, Robert W.; Parsons, Kathryn; Fields, Carter; Lewis Phillips, Gail D.; Friedman, Lori S.; Sampath, Deepak; Sliwkowski, Mark X.

     View on PubMed

  • Trastuzumab Emtansine (T-DM1): A Novel Agent for Targeting HER2(+) Breast Cancer.

    Clinical Breast Cancer, Oct 2011, V11, N5, , pp 275-282. ISSN: 1526-8209.

    Burris, Howard A III; Tibbitts, Jay; Holden, Scott N; Sliwkowski, Mark X; Phillips, Gail D Lewis

     View on PubMed

  • A Two-in-One Antibody against HER3 and EGFR Has Superior Inhibitory Activity Compared with Monospecific Antibodies

    Cancer Cell, 18 Oct 2011, v20(4), p.472-86, ISSN: 1878-3686

    Gabriele Schaefer; Lauric Haber; Lisa M. Crocker; Steven Shia; Lily Shao; Donald Dowbenko; Klara Totpal; Anne Wong; Chingwwei V. Lee; Scott Stawicki; Robyn Clark; Carter Fields; Gail D. Lewis Phillips; Rodney A. Prell; Dimitry M. Danilenko; Yvonne Franke; Jean-Philippe Stephan; Jiyoung Hwang; Yan Wu; Jenny Bostrom, Mark X. Sliwkowski; Germaine Fuh; Charles Eigenbrot

     View on PubMed

  • Trastuzumab emtansine: a unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer.

    Clinical Cancer Research, 15 Oct 2011, vol. 17, no. 20, p. 6437-47, ISSN: 1078-0432.

    Lorusso, Patricia M; Weiss, Denise; Guardino, Ellie; Girish, Sandhya; Sliwkowski, Mark X

     View on PubMed

  • On the Road to Combinations of Targeted Therapies: PPM1H Phosphatase as a Suppressor of Trastuzumab Resistance

    Cancer Discovery,14 September 2011, V1(4), p.285-286, ISSN: 2159-8274, eISSN: 2159-8290

    Sliwkowski, Mark; Stern, Howard;

     View on PubMed

  • PPM1H Is a p27 Phosphatase Implicated in Trastuzumab Resistance.

    Cancer Discovery, 2011, V1, N4, SEP, pp 326-337, ISSN: 2159-8274.

    Lee, Hoeflich Si Tuen; Thinh, Q Pham; Dowbenko, Don; Munroe, Xander; Lee, James; Li, Li; Zhou, Wei; Haverty, Peter M; Pujara, Kanan; Stinson, Jeremy; Chan, Sara M; Eastham, Anderson Jeffrey; Pandita, Ajay; Seshagiri, Somasekar; Hoeflich, Klaus P; Turashvili, Gulisa; Gelmon, Karen A; Aparicio, Samuel A; Davis, David P; Sliwkowski, Mark X; Stern, Howard M

     View on PubMed

  • Conjugation site modulates the stability and biological activity of antibody drug conjugates.

    Proceedings of the American Association for Cancer Research Annual Meeting, 2010, ISSN: 0197-016X

    Shen, B.; Xu, K.; Liu, L.; Parsons, K.; Bhakta, S.; Raab, H.; Flagella, K.; Spencer, S.; Kaur, S.; Scheller, R.; Sliwkowski, M.; Polakis, P.; Junutula, J.

  • Dual targeting of HER2: Enhanced antitumor efficacy of trastuzumab- DMI combined with pertuzumab.

    Proceedings of the American Association for Cancer Research Annual Meeting, 2010, ISSN: 0197-016X

    Fields, C.; Crocker, L.; Sliwkowski, M.; Phillips, G.

  • Engineered thio-trastuzumab-DM1 conjugate with an improved therapeutic index to target HER2-positive breast cancer.

    Clinical Cancer Research, 2010, ISSN: 1078-0432

    Junutula, J.; Flagella, K.; Graham, R.; Parsons, K.; Ha, E.; Raab, H.; Bhakta, S.; Nguyen, T.; Dugger, D.; Li, G.; Mai, E.; Lewis Phillips, G.; Hiraragi, H.; Fuji, R.; Tibbitts, J.; Vandlen, R.; Spencer, S.; Scheller, R.; Polakis, P.; Sliwkowski, M.

     View on PubMed

  • Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer.

    Breast Cancer Research and Treatment, 2011, ISSN: 1573-7217

    Junttila, Teemu; Li, Guangmin.; Parsons, Kathryn.; Phillips, Gail L.; Sliwkowski, Mark

     View on PubMed

  • Superior In vivo Efficacy of Afucosylated Trastuzumab in the Treatment of HER2-Amplified Breast Cancer.

    Cancer Research, 2010, ISSN: 1538-7445

    Junttila, T.; Parsons, K.; Olsson, C.; Lu, Y.; Xin, Y.; Theriault, J.; Crocker, L.; Pabonan, O.; Baginski, T.; Meng, G.; Totpal, K.; Kelley, R.; Sliwkowski, M.

  • Modeling the efficacy of trastuzumab-DM1, an antibody drug conjugate, in mice.

    Journal of Pharmacokinetics and Pharmacodynamics, 2010, ISSN: 1567-567X

    Jumbe, N.; Yan, X.; Leipold, D.; Crocker, L.; Dugger, D.; Mai, E.; Sliwkowski, M.; Fielder, P.; Tibbitts, J.

  • Phase I Study of Trastuzumab-DM1, a HER2 Antibody-Drug Conjugate, Given Every 3 Weeks to Patients With HER2-Positive Metastatic Breast Cancer

    Journal of Clinical Oncology, 2010, ISSN: 1527-7755

    Krop, I.; Beeram, M.; Modi, S.; Jones, S.; Holden, S.; Yu, W.; Girish, S.; Tibbitts, J.; Yi, J.-H.; Sliwkowski, M.; Jacobson, F.; Lutzker, S.; Burris, H.

  • Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer.

    Journal of Clinical Oncology, 2010, ISSN: 0732-183X

    Makhija, S.; Amler, L.; Glenn, D.; Ueland, F.; Gold, M.; Dizon, D.; Paton, V.; Lin, C.; Januario, T.; Ng, K.; Strauss, A.; Kelsey, S.; Sliwkowski, M.; Matulonis, U.

  • Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab.

    Clinical Cancer Research, 2009, ISSN: 1078-0432

    Yao, E.; Zhou, W.; Lee-Hoeflich, S.T.;Truong T.; Haverty, P.M.;Eastham-Anderson, J.; Lewin-Koh, N.; Gunter, B.; Belvin, M.; Murray, L.J.; Friedman, L.S.; Sliwkowski, M.X.; Hoeflich, K.P.

  • Toward an effective targeted chemotherapy for multiple myeloma.[comment].

    Clinical Cancer Research, 2009, ISSN: 1078-0432

    Polson, A.G.; Sliwkowski, M.X.

  • Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941.

    Cancer Cell, 2009, ISSN: 1535-6108

    Junttila, T.T.; Akita, R.W.; Parsons, K.; Fields, C.; Lewis Phillips, G.D.; Friedman, L.S.; Sampath, D.; Sliwkowski, M.X.

  • Suppression of breast cancer cell growth by a monoclonal antibody targeting cleavable ErbB4 isoforms.

    Oncogene, 2009, ISSN: 0950-9232

    Hollmen, M.; Maatta, J.A.; Bald, L.; Sliwkowski, M.X.; Elenius, K.

• Education
  • National Institutes of Health, National Heart, Lung and Blood Institute, Staff Fellow – 1985
  • North Carolina State University, Department of Biochemistry, Ph.D. – 1981
  • University of Delaware, Department of Animal Science and Agricultural Biochemistry, B.S. – 1976
• Awards & Honors
  • Industry Scientist of the Year, Pharmaceutical Achievement Award – 2005
  • Industrial Initiative for Science and Math Education Award – 1989
  • Triton Research & Development Award – 1989
  • American Society of Biological Chemistry Travel Grant – 1985