Article
Oncology
Emily N. Risdon, Cindy H. Chau, Douglas K. Price, Oliver Sartor, William D. Figg
Summary: The U.S. FDA approved two PARP inhibitors, olaparib and rucaparib, for treating metastatic castrate resistant prostate cancer with biomarker-positive patients. The benefits of PARP inhibition have been well studied in patients with BRCA1 and BRCA2 mutations, and there is potential to expand the use of PARP inhibitors to mutations in other non-BRCA DNA damage repair genes, increasing the patient population that could benefit from this treatment. Understanding the significance of PARP inhibitor-sensitizing alterations in other common non-BRCA DDR genes will help guide clinical decisions to offer targeted treatment options to a wider population of patients.
Review
Oncology
Kristi Y. Lee, Cindy H. Chau, Douglas K. Price, William D. Figg
Summary: The majority of the human proteome remains uncharacterized, hindering research on drug resistance mechanisms and advanced treatments. Chemical proteomics, specifically activity-based protein profiling (ABPP), offers a powerful solution for profiling and developing cancer therapeutics. In a recent study, ABPP was used to investigate the KLK family and their role in prostate cancer progression, revealing androgen receptor-dependent activity.
CANCER BIOLOGY & THERAPY
(2022)
Article
Oncology
Cindy H. Chau, Cathee Till, Douglas K. Price, Phyllis J. Goodman, Marian L. Neuhouser, Michael N. Pollak, Ian M. Thompson, William D. Figg
Summary: The molecular mechanisms linking obesity to prostate cancer involve steroid hormone and insulin/insulin-like growth factor 1 (IGF1) pathways. This study investigated the associations between circulating serum markers (e.g. androgens and IGFs/IGFBPs) and body mass index (BMI), as well as their role in modifying the association between obesity and prostate cancer risk. The results showed that there were significant associations between BMI and serum steroids and IGFs/IGFBPs, and the IGF1 axis played a significant role in the association between obesity and low- and high-grade prostate cancer.
ENDOCRINE-RELATED CANCER
(2022)
Article
Oncology
Cecilia Monge, Erica C. Pehrsson, Changqing Xie, Austin G. Duffy, Donna Mabry, Bradford J. Wood, David E. Kleiner, Seth M. Steinberg, William D. Figg, Bernadette Redd, Anuradha Budhu, Sophie Wang, Mayank Tandon, Lichun Ma, Xin Wei Wang, Tim F. Greten
Summary: This study demonstrates that the combination of capecitabine and oxaliplatin with pembrolizumab is well tolerated and potentially effective in treating refractory advanced biliary tract carcinoma. The study highlights the importance of a design framework for the precise characterization of individual tumors.
Article
Oncology
Tristan M. Sissung, William D. Figg
Summary: This article analyzes phase I clinical studies in oncology with a focus on pharmacogenetics. The findings suggest that current studies have small sample sizes, evaluate a limited number of genetic variants, and lack sufficient justification for pharmacogenetic hypotheses. Future studies should consider population heterogeneity and other confounding factors to optimize the design of phase I clinical trials and answer important scientific questions.
Article
Cell Biology
Ashlyn Parkhurst, Sabrina Z. Wang, Tyler R. Findlay, Kristen J. Malebranche, Arman Odabas, Jesse Alt, Micah J. Maxwell, Harpreet Kaur, Cody J. Peer, William D. Figg, Katherine E. Warren, Barbara S. Slusher, Charles G. Eberhart, Eric H. Raabe, Jeffrey A. Rubens
Summary: By combining the mTOR inhibitor TAK-228 with the BH3 mimetic Obatoclax, researchers have found that they can slow tumor growth, induce apoptosis and cell death in atypical teratoid/rhabdoid tumors (AT/RT), and activate the integrative stress response. This combination therapy shows promise in improving survival rates in AT/RT.
CELL DEATH & DISEASE
(2022)
Article
Pharmacology & Pharmacy
Yang Li, Yan Jin, Hanieh Taheri, Keith T. Schmidt, Alice A. Gibson, Stefan A. J. Buck, Eric D. Eisenmann, Ron H. J. Mathijssen, William D. Figg, Sharyn D. Baker, Alex Sparreboom, Shuiying Hu
Summary: In recent years, various endogenous compounds have been proposed as potential biomarkers for hepatic uptake transporters. This study used a bottom-up metabolomics screening approach to identify the bile acid CDCA-24G as a sensitive and selective endogenous biomarker for OATP1B-type transport function.
Article
Biochemical Research Methods
William J. Richardson, Sara M. Zimmerman, Annieka Reno, Natalia Corvalan Cabanas, Oluwatobi Arisa, Udo Rudloff, William D. Figg, Cody J. Peer
Summary: Metarrestin is a small molecule inhibitor that targets the perinucleolar compartment associated with metastasis. A uHPLC-MS/MS assay was developed to determine its pharmacokinetic profile in human plasma. The validated method is simple, sensitive, and clinically applicable.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Editorial Material
Oncology
Sharyn D. Baker, Susan E. Bates, Gabriel A. Brooks, William L. Dahut, Robert B. Diasio, Wafik S. El-Deiry, William E. Evans, William D. Figg, Dan L. Hertz, J. Kevin Hicks, Suneel Kamath, Pashtoon Murtaza Kasi, Todd C. Knepper, Howard L. McLeod, Peter H. O'Donnell, Mary V. Relling, Michelle A. Rudek, Tristan M. Sissung, D. Max Smith, Alex Sparreboom, Sandra M. Swain, Christine M. Walko
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Katherine E. Warren, Gilbert Vezina, Mark Krailo, Linda Springer, Allen Buxton, Cody J. Peer, William D. Figg, Chris William-Hughes, Sandy Kessel, Maryam Fouladi, Amar Gajjar, Daniel Bowers
Summary: This study investigated the efficacy of lenalidomide in treating children with low-grade glioma, and found that lenalidomide has a certain level of therapeutic activity. Low-dose (20 mg/m(2)/dose administered once daily x 21 days of each 28-day cycle) lenalidomide appears to have better tolerability with comparable activity.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Elijah R. Sommer, Giulia C. Napoli, Cindy H. Chau, Douglas K. Price, William D. Figg
Summary: Identification of actionable drug targets remains a bottleneck in successful drug development for metastatic cancers. The use of CRISPR-Cas9 for targeted genomic edits has accelerated discoveries in developmental biology. Recent work has integrated CRISPR-Cas9-based lineage tracing with single-cell transcriptomics in cancer metastasis, highlighting the importance of single-cell lineage tracing in oncology drug development and the potential of computational approaches in reshaping cancer drug discovery.
Article
Public, Environmental & Occupational Health
Kristi Y. Lee, Erica L. Beatson, Seth M. Steinberg, Cindy H. Chau, Douglas K. Price, William D. Figg
Summary: As the era of cancer genomics expands, the disproportionate rates of prostate cancer incidence and mortality by race are increasingly relevant in clinical settings. While Black men are most affected by prostate cancer, the opposite is observed for Asian men, creating a basis for exploring genomic pathways involved in mediating these opposing trends. Limited by sample size, studies on racial differences may be improved with expanding collaborations between research institutions to investigate health disparities from a genomics perspective. This study analyzed mutation and copy number frequencies of select genes in primary and metastatic tumor samples using GENIE v11, and identified differentially expressed genes highly upregulated in one race and subsequently downregulated in another using the TCGA race cohort.
JOURNAL OF RACIAL AND ETHNIC HEALTH DISPARITIES
(2023)
Review
Oncology
Austin Wesevich, Daniel A. A. Goldstein, Koosha Paydary, Cody J. J. Peer, William D. D. Figg, Mark J. J. Ratain
Summary: Immune checkpoint inhibitors (ICIs) have been approved for treating various types of cancer, but their doses have not been optimised. Optimising the doses could reduce the risk and severity of adverse events and provide cost-saving opportunities through interventional pharmacoeconomic strategies.
BRITISH JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Edjah K. Nduom, John Glod, Desmond A. Brown, Margaret Fagan, Mahalia Dalmage, John Heiss, Seth M. Steinberg, Cody Peer, William D. Figg, Sadhana Jackson
Summary: Diffuse midline gliomas (DMG) are aggressive brain tumors with low survival rates. The function of the blood-brain barrier (BBB) contributes to treatment failure. This clinical trial aims to use intratumoral microdialysis sampling to understand drug permeability and its relationship to DMG treatment response. The findings of this study could improve drug delivery efficacy and influence prognostic and diagnostic decisions for this lethal disease with limited treatment options.
Article
Oncology
Jerry T. Wu, Adam Cheuk, Kristine Isanogle, Christina Robinson, Xiaohu Zhang, Michele Ceribelli, Erin Beck, Paul Shinn, Carleen Klumpp-Thomas, Kelli M. Wilson, Crystal Mcknight, Zina Itkin, Hiroshi Sotome, Hiroshi Hirai, Elizabeth Calleja, Volker Wacheck, Brad Gouker, Cody J. Peer, Natalia Corvalan, David Milewski, Yong Y. Kim, William D. Figg, Elijah F. Edmondson, Craig J. Thomas, Simone Difilippantonio, Jun S. Wei, Javed Khan
Summary: Rhabdomyosarcoma (RMS) is a common pediatric soft tissue sarcoma. Futibatinib, an irreversible pan-FGFR inhibitor, shows efficacy in inhibiting the growth of RMS cell lines in vitro by targeting FGFR4. However, limited efficacy is observed in animal models, suggesting the need for alternative treatment strategies.