Genentech: Gail Lewis | Distinguished Scientist, Discovery Oncology - Antibody-drug Conjugates, PI3K/AKT pathway inhibitors, Research Biology

Scientists / Our Scientists

"There’s no end. There’s no done. And we won’t stop."

Years at Genentech

Publications at Genentech

Awards & Honors

I was hired at Genentech to study tumor cell killing mechanisms of TNF-alpha and interferon-gamma. We discovered that activated tyrosine kinases conferred resistance to tumor cell killing by TNF-alpha. We were investigating which kinases induced TNF-a resistance at the same time that the HER2 receptor tyrosine kinase was discovered and characterized, also at Genentech. This work came together when we demonstrated that overexpressed/activated HER2 conferred resistance to TNF-a and that this was prevented by treatment with HER2-blocking antibodies.

Our focus shifted to studying mechanisms by which HER2 antibodies inhibited growth only of HER2-overexpressing breast cancer cells, which resulted in the identification of 2 HER2 antibodies that blocked growth by different mechanisms.

We then pivoted from antibodies to studying antibody-drug conjugates for selective delivery of cell killing agents to tumor cells. This has remained the primary focus of my lab, covering ADCs for both solid tumors and hematologic indications. We also study small molecule inhibitors of signal transduction pathways downstream of receptor tyrosine kinases.

Featured Publication

The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results

Nat Commun. 2024;15:466-480

Lewis GD, Li G, Guo J, Yu S-F, Fields CT, et al.

View Abstract

Trastuzumab does not bind rat or mouse ErbB2/neu: implications for selection of nonclinical safety models for trastuzumab-based therapeutics

Breast Cancer Res Treat 2022;191:303-317

Lewis Phillips G, Guo J, Kiefer JR, Proctor W, Bumbaca Yadav D, Dybdal N, Shen B-Q.

View Abstract

Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells

Mol Cancer Ther 2018;17:1441-1453

Li G, Guo J, Shen B-Q, Bumbaca Yadav D, Sliwkowski MX, Crocker LM, Lacap JA, Lewis Phillips GD

View Abstract

Trastuzumab uptake and its relation to efficacy in an animal model of HER2-positive breast cancer brain metastasis

Breast Cancer Res Treat 2017;164:581-591

Lewis Phillips GD, Nishimura MC, Arca Lacap J, Kharbanda S, Mai E, Tien J,et al.

View Abstract

ADCs approved for use: Trastuzumab emtansine (Kadcyla®, T-DM1) in patients with previously treated HER2-positive metastatic breast cancer.

In: Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer 2016;chapter 14;345-380. Olivier, K and Hurvitz, S (ed.), John Wiley & Sons, Inc., New Jersey

Lewis Phillips GD, de Haas S, Girish S, Guardino, E.

View Abstract

Relationship between Tumor Biomarkers and Efficacy in EMILIA, a Phase III Study of Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer.

Clin Cancer Res 2016;22:3755-3763

Baselga J, Lewis Phillips GD, Verma S, Ro J, Huober J, Guardino AE, et al.

View Abstract

In Vitro Skin Models and Their Predictability in Defining Normal and Disease Biology, Pharmacology, and Toxicity.

Toxicol Pathol 2016;44:555-563

Danilenko DM, Lewis Phillips GD, Diaz, D.

View Abstract

Dual targeting of HER2-positive cancer with trastuzumab emtansine (T-DM1) and pertuzumab: critical role for neuregulin blockade in anti-tumor response to combination therapy.

Clin Cancer Res 2014;20:456-468

Lewis Phillips GD, Fields CT, Li G, Dowbenko D, Schaefer G, et al.

View Abstract

Antibody-Drug Conjugates and Immunotoxins: from Pre-Clinical Development to Therapeutic Applications.

Cancer Drug Discovery and Development Series 2008;68:9280-9290

Gail Lewis Phillips, editor;

View Abstract

Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate.

Cancer Res 2008;68:9280-929

Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, Blattler WA, Lambert JM, Chari RVJ, Lutz RJ, Wong WLT, Jacobson FS, Koeppen, H., Schwall, R.H., Kenkare-Mitra, S.R., Spencer, S.D. and Sliwkowski MX.

View Abstract

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;56:1457-1465

Lewis G.D, Lofgren J.A, McMurtrey AE, Nuijens A, Fendly BM, Bauer K D, Sliwkowski MX.

View Abstract

Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies.

Cancer Immunol Immunother 1993;37:255-263

Lewis GD, Figari I S, Fendly BM, Wong WL, Carter PJ, Gorman C, Shepard HM.

View Abstract

My early work at Genentech focused on investigating the biology of cell surface receptor tyrosine kinases and the potential for therapeutic targeting with antibodies. From there, we began a journey of studying antibody-drug conjugates - i.e., the utilization of tumor-selective antibodies to target cancer killing agents to tumor cells.

We have worked for many years to understand what comprises an optimal tumor target, which type of linker to use for conjugation of the killing agent to the antibody, and which cell killing agents give the most desired effects in terms of both efficacy and safety. Our ADC efforts cover breast cancer and other solid tumors as well as different hematologic malignancies.

In addition, my lab works on agents targeting signal transduction pathways (HER2, PI3K/AKT) to gain understanding of mechanisms of action across tumor indications.

A homogeneous high-DAR antibody-drug conjugate platform combining THIOMAB antibodies and XTEN polypeptides†

Chemical Science, ISSN: 20416539 20416520

Neelie Zacharias; Vladimir N. Podust; Kimberly K. Kajihara; Douglas Leipold; Geoffrey Del Rosario; Desiree Thayer; Emily Dong; Maciej Paluch; David Fischer; Kai Zheng; Corinna Lei; Jintang He; Carl Ng; Dian Su; Luna Liu; Shabkhaiz Masih; William S. Sawyer; Jeff N. Tinianow; Jan Marik; Victor Yip; Guangmin Li; Josefa Chuh; J. Hiroshi Morisaki; Summer Park; Bing Zheng; Hilda Hernandez-Barry; Kelly M. Loyet; Min Xu; Katherine R. Kozak; Gail Lewis Phillips; Shen; Cong Wu; Keyang Xu; Shang-Fan Yu; Amrita Kamath; Rebecca K. Rowntree; Dorothea Reilly; Thomas H. Pillow; Andrew G. Polson; Volker Schellenberger; Wouter L. W. Hazenbos; Jack D. Sadowsky

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Gail Lewis

Distinguished Scientist, Discovery Oncology - Antibody-drug Conjugates, PI3K/AKT pathway inhibitors, Research Biology

Featured Publication

The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results

Trastuzumab does not bind rat or mouse ErbB2/neu: implications for selection of nonclinical safety models for trastuzumab-based therapeutics

Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells

Trastuzumab uptake and its relation to efficacy in an animal model of HER2-positive breast cancer brain metastasis

ADCs approved for use: Trastuzumab emtansine (Kadcyla®, T-DM1) in patients with previously treated HER2-positive metastatic breast cancer.

Relationship between Tumor Biomarkers and Efficacy in EMILIA, a Phase III Study of Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer.

In Vitro Skin Models and Their Predictability in Defining Normal and Disease Biology, Pharmacology, and Toxicity.

Dual targeting of HER2-positive cancer with trastuzumab emtansine (T-DM1) and pertuzumab: critical role for neuregulin blockade in anti-tumor response to combination therapy.

Antibody-Drug Conjugates and Immunotoxins: from Pre-Clinical Development to Therapeutic Applications.

Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate.

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.

Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies.

Breast Cancer

In Her Own Words