Mathew Lab
The Mathew laboratory is focused on the investigation of epithelial-stromal interactions that drive the metastatic progression of human malignancies and the development of novel therapeutics that target these mechanisms.

Overview

Our major focus has been on prostate cancer and its progression to the highly-conserved phenotype of bone metastases. Our laboratory at Tufts Medical Center has identified a seed-and-soil mechanism involving integrin cooperativity in tumor-stromal interactions of prostate cancer and developed a proprietary bispecific antibody to target this cooperative biology (Joshi Cell Adh Migr 2016, Joshi et al, AACR 2018). We have traced survival pathways mediated by integrins in prostate cancer cells to the BCL-XL protein and have defined synthetic lethality in PTEN-deficient prostate cancer cells with the combination of PI3K/AKT and BCL-XL inhibition (Ren et al, MCR 2016; Ren et al, AACR 2018).  Our long-term goal is to translate these advances to the clinic in prostate cancer and other malignancies which share this thematic biology.
Principal investigator + Staff

Paul Mathew, MD is a faculty member in the Department of Hematology-Oncology at Tufts Medical Center from 2009-present. He is principally responsible for clinical care of all genitourinary malignancies (prostate, kidney, testis, penile and bladder cancer) and experimental therapeutics in these tumors at Tufts Medical Center. Dr Mathew completed his Internal Medicine Residency at Cook County Hospital, Chicago IL and Hematology-Oncology Fellowship at Mayo Clinic, Rochester MN. His prior faculty position was in the Division of Genitourinary Medical Oncology at MD Anderson Cancer Center, Houston, 2001-2009.

Staff members:

Paul Mathew, MD 
Raghav Joshi, BSc 
Wenying Ren, PhD
Publications

Prostate cancer and experimental therapeutics

Abstracts:

  1. Joshi R, Ren W, Mathew P. Superior targeting of tumor-stromal interactions and endothelial migration with a bispecific antibody to α5 and αv integrins Proceedings of the Annual Association of Cancer Research 2018, Chicago, IL.
  2. Ren W, Joshi R, Mathew P. A potent BH3 mimetic targeting BCL-XL induces apoptosis regulated by PTEN loss and integrin alpha 5 in prostate cancer cells Proceedings of the Annual Association of Cancer Research 2018, Washington D.C.
  3. Joshi R, Ren W, Mathew P. MEK signaling marks a subgroup of PTEN-deficient tumors with resistance to synthetic lethality with PI3K/AKT and BCL-XL inhibition. Proceedings of the Annual Association of Cancer Research 2017, Washington D.C.
  4. Flores JP, Mathew P. Combination therapy with enzalutamide and the poly (ADP-ribose) polymerase-1 (PARP1) inhibitor niraparib in castration-resistant prostate cancer (CRPC): HCRN GU 14-202, J Clin Oncol 34, 2016 (suppl; abstr TPS5095)
  5. Ren W, Joshi R, Mathew P. Synergistic apoptosis induced by combined PI3 kinase and bcl-xl inhibition in genotypic subsets of prostate cancer is attenuated by a feedback signaling loop via the alpha-5 integrin. American Association of Cancer Research Annual Meeting 2016, New Orleans. Abstract #5091
  6. Joshi R, Goihberg E, Pilichowska M, Mathew P. The interaction of epithelial α5β1 integrin and stromal fibronectin is a candidate seed-and-soil mechanism in prostate cancer and bone metastases. American Association of Cancer Research Annual Meeting 2015, Philadelphia. Abstract #2378
Contact us

To contact the Mathew Lab, please email Paul Mathew at pmathew@tuftsmedicalcenter.org
Research focus area

Prostate cancer and bone metastases; integrin cooperativity in epithelial-stromal interactions; synthetic lethality in PTEN-deficient prostate cancer; clinical translation of experimental therapeutics in prostate cancer.