Gedatolisib

2021 San Antonio Breast Cancer Symposium (SABCS)

Phase Ib expansion study of gedatolisib in combination with palbociclib and endocrine therapy in women with ER+ metastatic breast cancer

Rachel M. Layman, Robert Wesolowski, Hyo Han, Jennifer M. Specht, Erica M. Stringer-Reasor, E. Claire Dees, Peter Kabos, Ingrid A. Mayer, Ulka Vaishampayan, Janice Lu, Keerthi Gogineni, Aditya Bardia, Anne F. Schott, Maysa M. Abu-Khalaf, Doug Hawkins, Brian Sullivan, Igor Gorbatchevsky, Hope S. Rugo

2021 San Antonio Breast Cancer Symposium (SABCS)

Phase II study of trastuzumab biosimilar (Herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy: KM-10A (KCSG BR 18-13) interim analysis

Ju Won Kim, Hee Kyung Ahn, Jong Gwon Choi, Yee Soo Chae, Gyeong-Won Lee, KeonUk Park, Eunmi Lee, Sung Hoon Sim, Jee Hyun Kim, Yeon Hee Park, Miso Ki1, Jin Hyun Park, Jeong Eun Kim, Han Jo Kim, Mi Sun Ahn, So Yeon Oh, Min Hwan Kim, Su-Jin Koh, Kyoung Eun Lee, Myoung Joo Kang, Jae Ho Byun, Joo young Ha, Jung Hye Kwon, Joo Young Jung, Su Ee Lee, Inhae Park, and Kyong Hwa Park

Clinical Cancer Research

Phase I dose-escalation study of the dual PI3K-mTORC1/2 inhibitor gedatolisib in combination with paclitaxel and carboplatin in patients with advanced solid tumors. Clin Cancer Res;27:5012–9, 2021

Ilaria Colombo, Sofia Genta, Federica Martorana, Monia Guidi, Milo Frattini, Eleftherios Pierre Samartzis, Simone Brandt, Sheila Gaggetta, Laura Moser, Mariarosa Pascale, Tatiana Terrot, Cristiana Sessa, and Anastasios Stathis

2021 American Associated of Cancer Research (AACR)

Subgroup of HER2-negative breast cancer patients with hyperactive RAS network signaling identified: dynamic pathway activity test identifies patients that may benefit from PI3K/mTOR or PI3K/mTOR/BCL inhibitors

Salmaan Khan, Adrish Sen, Catherine Kuzmicki, Ian MacNeil, Aaron Broege, Sarah Mutka, Kelly Brass, Ky McCracken, Laura Milligan, Kaija Kottke, Brian Sullivan, Lance G. Laing

2021 American Associated of Cancer Research (AACR)

Subgroup of ovarian cancer patients with hyperactive RAS network signaling identified: dynamic pathway activity test identifies patients that may benefit from PI3K/mTOR or PI3K/mTOR/BCL inhibitors

Stefano Rossetti, Aaron Broege, Joanna Sabat, Shu Wiley, Salmaan Khan, Catherine Kuzmicki, Ian MacNeil, Brian Sullivan, Lance Laing

Gynecologic Oncology

A randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer, Gynecologic Oncology 142, 62–69, 2016

Josep María del Campo, Michael Birrer, Craig Davis, Keiichi Fujiwara, Ashwin Gollerkeri, Martin Gore, Brett Houk, Susie Lau, Andres Poveda, Antonio González-Martín,  Carolyn Muller, Kei Muro, Kristen Pierce, Mie Suzuki, Jennifer Vermette, Amit Oza

Clinical Cancer Research

First-in human study of PF-05212384 (PKI-587), a small-molecule, intravenous, dual inhibitor of PI3K and mTOR in patients with advanced cancer. Clin Cancer Res; 21(8) April 15, 2015

Geoffrey I. Shapiro, Katherine M. Bell-McGuinn, Julian R. Molina, Johanna Bendell, James Spicer, Eunice L. Kwak, Susan S. Pandya, Robert Millham, Gary Borzillo, Kristen J. Pierce, Lixin Han, Brett E. Houk, Jorge D. Gallo, Maria Alsina, Irene Brana, and Josep Tabernero

Clinical Cancer Research

Antitumor Efficacy of PKI-587, a Highly Potent Dual PI3K/mTOR Kinase Inhibitor, Clin Cancer Res; 17(10); 3193–203, 2011

Robert Mallon, Larry R. Feldberg, Judy Lucas, Inder Chaudhary, Christoph Dehnhardt, Efren Delos Santos, Zecheng Chen, Osvaldo dos Santos, Semiramis Ayral-Kaloustian, Aranapakam Venkatesan, and Irwin Hollander

Journal of Medicinal Chemistry

Bis(morpholino-1,3,5-triazine) Derivatives: Potent Adenosine 50-Triphosphate Competitive Phosphatidylinositol-3-kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of Compound 26 (PKI-587), a Highly Efficacious Dual Inhibitor. J. Med. Chem. 2010, 53, 6, 2636–2645

Aranapakam M Venkatesan, Christoph M Dehnhardt, Efren Delos Santos, Zecheng Chen, Osvaldo Dos Santos, Semiramis Ayral-Kaloustian, Gulnaz Khafizova, Natasja Brooijmans, Robert Mallon, Irwin Hollander, Larry Feldberg, Judy Lucas, Ker Yu, James Gibbons, Robert T Abraham, Inder Chaudhary, Tarek S Mansour

CELSignia

Cell Communication and Signaling

Functional signaling test identifies HER2 negative breast cancer patients who may benefit from c-Met and pan-HER combination therapy. Cell Communication and Signaling, 20:4, 2022

Ian A. MacNeil, Salmaan A. Khan, Adrish Sen, Sajjad M. Soltani, David J. Burns, Brian F. Sullivan & Lance G. Laing

Journal of Cancer Research and Clinical Oncology

New HER2‐negative breast cancer subtype responsive to anti‐HER2 therapy identified. Journal of Cancer Research and Clinical Oncology 2020;146:605-619

Ian A. MacNeil, David J. Burns, Benjamin E. Rich, Sajjad M. Soltani, Samantha Kharbush, Nicole G. Osterhaus, Brian F. Sullivan, Douglas M. Hawkins, Jodie R. Pietruska, Lance G. Laing

2020 American Association of Cancer Research (AACR)

Hyperactive c-Met and ErbB signaling detected in a sub-group of ovarian patient tumors:
Patient sub-group may benefit from c-Met and pan-HER combination therapy

Stefano Rossetti, Catherine Kuzmicki, Aaron Broege, Joanna Sabat, Salmaan Khan, Ian MacNeil, Brian Sullivan, Lance Laing

2020 American Society of Clinical Oncology (ASCO)

Test measuring signaling activity in live patient tumor cells identifies PI3KCA WT patients who may benefit from PIK3 inhibitors

Lance G Laing, Salmaan Khan, Ian A MacNeil, Catherine Kuzmicki, Benjamin Rich, Abhay Shukla, Kelly Brass, Brian Sullivan

2019 San Antonio Breast Cancer Symposium (SABCS)

Sub-Group of PIK3CA WT breast cancer patients have hyperactive S1P and LPA signaling tumors responsive to PI3K inhibitors: functional signaling test identifies new patient group who may benefit from PI3K inhibitors

Lance G Laing, Salmaan Khan, Ian A MacNeil, Catherine Kuzmicki, Samantha Kharbush, Benjamin Rich, Abhay Shukla, Kelly Brass, Brian Sullivan

2018 San Antonio Breast Cancer Symposium (SABCS)

Evaluation of pan-HER and c-MET inhibitors tested ex vivo in live primary HER2- breast cancer cells with hyperactive c-MET and ErbB family signaling

Laing, L., Burns, D., Khan, S., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Kharbush, S., Broege, AM., Brass, K., Mutka, S., Sullivan. B

2018 San Antonio Breast Cancer Symposium (SABCS)

Evaluating contribution of hyperactive c-Met and ErbB signaling to tumor progression in mouse breast tumor xenografts: an in vivo study of c-Met and ErbB targeted therapies

Laing, L., Burns, D., Khan, S., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Kharbush, S., Brass, K., Sullivan. B

2018 San Antonio Breast Cancer Symposium (SABCS)

Sub-group of HER2- breast cancer patients with hyperactive and co-involved c-Met and ErbB pathways identified: functional signal profiling test identifies patient group that may benefit from c-Met and pan-HER combination therapy

Laing, L., Burns, D., Khan, S., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Kharbush, S., Brass, K., Broege, AM., Mutka, S., Sullivan. B

2018 American Society of Clinical Oncology (ASCO)

Live tumor cell functional analysis and a xenograft model find co-activated c-Met and ErbB signaling in HER2-negative breast cancer

Lance G Laing, David J Burns, Salmaan Khan, Ian A MacNeil, Benjamin E Rich, Sajjad M. Soltani, Samantha Myhre, Brian F Sullivan

2018 Miami Breast Cancer Conference

A phase 2 study of neoadjuvant chemotherapy plus trastuzumab and pertuzumab in HER2-negative breast cancer patients with abnormal HER2-driven signaling transduction (NCT03412643)

Eleftherios P. Mamounas, MD, MPH; Lance G Laing

BMC Cancer

Development of a test that measures real-time HER2 signaling activity in live breast cancer cell lines and primary cells. BMC Cancer. 2017 March 17:199

Huang, Y., Burns, D., Rich, B., MacNeil, I., Dandapat, A., Soltani, S., Myhre, S., Sullivan, B., Lange, C., Furcht, L., Laing, L.

Oncotarget

A functional signal profiling test for identifying a subset of HER2-negative breast cancers with abnormal amplified HER2 signaling activity. Oncotarget. 2016 Oct 5;7(48) 78577-78590

Huang, Y., Burns, D., Rich, B., MacNeil, I., Dandapat, A., Soltani, S., Myhre, S., Sullivan, B., Furcht, L., Lange, C., Hurvitz, S., & Laing, L.

2017 San Antonio Breast Cancer Symposium (SABCS)

Use of a functional signal profiling test to determine the prevalence of abnormal HER2-driven signaling activity in the HER2-negative breast cancer patient population: New patient group may benefit from anti-HER2 therapy

Lance G Laing, David J Burns, Ian A MacNeil, Benjamin E Rich, Sajjad M Soltani, Samantha Myhre, Brian F Sullivan

2017 American Society of Clinical Oncology (ASCO)

Measuring functional HER2-driven signaling status ex vivo to predict response to HER2 therapy: Results from a mouse breast tumor xenograft study

Laing, L., Burns, D., Huang, Y., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Sullivan, B.

2017 Miami Breast Cancer Conference

Inhibition of abnormal HER2-driven signaling by two HER2 targeted antibody drugs tested ex vivo in live primary HER2- breast cancer cell samples and HER2+ cell lines

2016 San Antonio Breast Cancer Symposium (SABCS)

Quantification of HER2-driven signaling (HER2S) inhibition of four different anti-HER2 drugs tested ex vivo in live primary HER2-negative breast cancer cell samples with abnormal HER2 signaling activity

Laing, L., Burns, D., Huang, Y., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Sullivan, B.

2016 San Antonio Breast Cancer Symposium (SABCS)

New method to measure functional HER2-driven signaling activity in primary tumor cells identifies HER2-negative breast cancers with abnormal HER2 signaling activity: New group of patients may benefit from anti-HER2 therapy

Laing, L., Burns, D., Huang, Y., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Sullivan, B.

2014 American Society of Clinical Oncology (ASCO)

Profiling of signaling pathways in live tumor cells to assess drug mechanism of action: A method to predict drug efficacy in a patient 

Laing, L., Huang, Y., MacNeil, I., Rich, B., Greeno, E.

2014 American Society of Clinical Oncology (ASCO)

Dynamic real-time signaling profiles of live primary cells characterize the response of PI3K and MAPK pathways in HER2+ breast cancer cells to attenuation with lapatinib: Tests of reproducibility of method

Laing, L., Huang, Y., MacNeil, I., Rich, B., Greeno, E.