The AACR-Bayer Stimulating Therapeutic Advances through Research Training (START) Grants represent an exciting initiative to encourage and support collaboration between academia and industry. The combined academic and industry training provided through this program will be invaluable to young investigators, allowing them to attain a comprehensive research experience. Projects have direct applicability and relevance to clinical translation and development in solid tumors and hematologic malignancies.

2020 Grantees

Research
ATP-binding cassette (ABC) transporters contribute to multidrug resistance (MDR) by pumping cytotoxic drugs out of cancer cells. Among ABC transporters, multidrug resistance protein 1 and multidrug resistance-associated protein 1 have been extensively investigated and are implicated in refractory and resistant (R/R) cancer in response to chemotherapy and antibody-drug conjugates (ADCs). As these transporters are potential targets for developing more efficacious cancer treatments, Dr. Hwang proposes dual-payload ADCs that are designed to mitigate MDR in cancer cells. These dual-payload ADCs can selectively co-deliver anti-cancer drugs and MDR inhibitors to cancer cells without harming healthy tissues that endogenously express ADC transporters. Blocking MDR activity through an inhibitor can prompt the accumulation of the co-delivered anti-cancer drug and kill tumor cells at lower ADC dosing.

Biography
Dr. Hwang received her PhD at Seoul National University. Her research focused on discovering and engineering antibodies through phage display technology for use as cancer therapeutics and medical imaging tools. Since joining The Scripps Research Institute in 2017, she has continued to work in the field of antibody therapy, specifically on the development of next-generation antibody-drug conjugates (ADCs) for cancer therapy. She has devoted a particular focus to developing new conjugation technologies for the generation of site-specific ADCs and new antibody carriers to improve their tumor tissue penetration.

Acknowledgement of Support
I am very honored to have been selected for the AACR-Bayer START Grant and appreciate the support of my mentors for this proposal. This award will allow me to acquire insight into industrial drug discovery and development, continue my research on antibody-based cancer therapeutics, and greatly facilitate my career development.

Research
Pancreatic cancer is one of the deadliest types of cancer with a five-year survival rate in the single digits. There are multiple subtypes of this malignancy, which includes adenosquamous carcinoma of the pancreas (ASCP), a highly aggressive tumor with the poorest clinical outcome out of all pancreatic cancers. Given recent studies showing that a considerable proportion of pancreatic cancers exhibit adenosquamous features, the need to better characterize ASCP and to explore its molecular dependencies is of great importance. Using a new mouse model that develops ASCP as well as patient-derived samples, Dr. Nakamura plans to uncover the key molecular drivers that govern the formation and progression of ASCP tumors.

Biography
Dr. Nakamura obtained her BSc, MSc, and PhD from the University of Tokyo in Japan. She is currently a postdoctoral fellow at the University of California San Diego. Her research focuses on understanding the molecular mechanisms regulating pancreatic cancer progression and aims to identify novel therapeutic targets for the disease.

Acknowledgement of Support
The AACR-Bayer START Grant provides me with an important opportunity to explore the therapeutic vulnerabilities of ASCP, an aggressive subtype of pancreatic cancer that has thus far not been investigated thoroughly. I am honored to receive this support and hope to use this opportunity to gain exciting insights for the field.

2018 Grantees

Research
It is hypothesized that androgen receptor (AR)-expressing metastatic castration-resistant prostate cancer bypasses AR pathway blockade through activation of the fibroblast growth factor (FGF) pathway. Thus, combined FGF and AR pathway inhibition can be more effective at preventing tumor cell proliferation and survival than AR inhibitor monotherapy. Dr. Labrecque has been investigating the efficacy of FGF and AR pathway inhibitors alone or in combination. The mechanisms driving combination therapy response and resistance will be determined through deep molecular profiling of treatment-resistant cell lines and PDX tumors. The overarching goal of the research is to support a combination therapy clinical trial in men with AR-expressing mCRPC.

Biography
Dr. Labrecque received his PhD in health sciences from Simon Fraser University. His doctoral research, supported through a Prostate Cancer Canada fellowship, focused on transcription factor crosstalk and the role of the retinoblastoma protein in hypoxic tumor microenvironments. He joined the Department of Urology at the University of Washington as an Institute for Prostate Cancer Research postdoctoral fellow. Currently, he uses metastatic biospecimens, patient-derived xenograft models, and in vitro approaches to understand and target the molecular underpinnings driving treatment-resistance in advanced prostate cancer.

Acknowledgement of Support
I am profoundly thankful and honored to be awarded an AACR-Bayer START Grant. This generous support and the opportunity to train with an industry leader like Bayer will be instrumental for my career development and will hopefully lead to better therapies for men with advanced prostate cancer.

Research
The cellular capacity to repair DNA damage via homologous recombination depends on DNA end resection. Utilizing genome editing tools to precisely calculate the extent of DNA resection, Dr. Subramanyam has been determining how DNA end resection is regulated. In addition, he has been characterizing the spatio-temporal dynamics of proteins involved in DNA end resection, using live cell super-resolution microscopy.

Biography
Dr. Subramanyam completed his PhD in Biochemistry at the University of Illinois at Urbana-Champaign, where he focused on understanding molecular mechanisms in DNA repair at a single molecule level. His postdoctoral research focuses on building on his experiences from graduate school to visualize molecular mechanisms of DNA repair within living cells.

Acknowledgement of Support
I thank the committee for appreciating and generously supporting my proposed work for the 2018 AACR-Bayer Stimulating Therapeutic Advances through Research Training Grant. In addition to facilitating my development as an independent scientist, I hope we can make significant inroads into further understanding the fundamental mechanisms that regulate DNA repair.