Alexandra Corella
Sander Frank, PhD
Two early-career scientists at Fred Hutchinson Cancer Research Center—Alexandra Corella and Sander Frank, PhD—have received grants to further their prostate cancer research.
Ms. Corella, a graduate research assistant, won a $25,000, 1-year fellowship from the Ford Foundation Fellowship Programs, which are administered by the National Academies of Sciences, Engineering, and Medicine. She will use the funding to complete her doctoral dissertation research on small cell neuroendocrine prostate cancer, which does not respond well to conventional therapies.
Dr. Frank, a postdoctoral research fellow, received a 3-year training fellowship of more than $210,000 from the -National Institutes of Health (NIH) to study how mutations in genes that control DNA repair promote tumor progression and whether these mutations may be exploited for targeted therapies. The NIH established the Ruth L. Kirschstein National Research Service Award for Individual Postdoctoral Fellows, otherwise known as an F32 award, to help postdoctoral students transition to independent research careers.
Both Ms. Corella and Dr. Frank work in the laboratory of Peter Nelson, MD, who holds the Endowed Chair for Prostate Cancer Research at Fred Hutch. Dr. Nelson co-leads the center’s multidisciplinary Program in Prostate Cancer Research. Dr. Frank is co-mentored by Valeri Vasioukhin, PhD, whose Fred Hutch lab studies model systems of prostate cancer progression.
Rare, Aggressive Prostate Cancer
Ms. Corella, who is completing her doctoral research through an interdisciplinary molecular and cellular biology PhD program is particularly interested in the mechanisms that enable small cell neuroendocrine prostate cancer to grow and thrive within the body, impervious to standard treatments for metastatic disease, such as androgen-blocking therapy. Such mechanisms have remained elusive due to the rarity of the disease and a lack of model systems with which to study it.
Already she has analyzed RNA-sequencing data from a panel of aggressive, small cell neuroendocrine tumors—not only from the prostate but also from Merkel cell carcinomas and small cell lung cancers. She has found that although these neuroendocrine cancers arise in different parts of the body, they share some 4,300 genes in common. She then analyzed these genes to see which ones may contain potentially “druggable” mutations that may respond to treatment.
One such mutation, BCL2, is highly expressed in patients with small cell neuroendocrine prostate cancer and other neuroendocrine cancers. She plans to devote the next phase of her dissertation research to investigating the biology of the role of BCL2 in aggressive prostate cancer.
Faulty DNA Repair
Dr. Frank joined Drs. Nelson’s and Vasioukhin’s labs in 2018 and is interested in understanding the role of DNA-repair gene mutations in prostate cancer. Genes in the DNA-repair pathway were recently found to be mutated in about 20% of advanced prostate cancers. Dr. Frank will use a combination of lab-grown cell lines and mouse models to test how the loss of BRCA1, BRCA2, and CDK12 can promote cancer progression and potentially sensitize tumors to certain therapies.
In Dr. Vasioukhin’s lab, Dr. Frank has helped generate mice with prostate-specific gene deletions to study how “knocking out” these genes affects prostate cancer development. In Dr. Nelson’s lab, he is working with cell lines and patient-derived xenograft models. Dr. Frank will combine his work in the two labs to test potential therapies against prostate cancers with DNA-repair loss. ■
