Genomic Characterization of Preclinical Prostate Cancer Cell Line Models.

As we move into the era of precision medicine, the growing relevance of genetic alterations to prostate cancer (PCa) development and treatment demonstrates the importance of characterizing preclinical models at the genomic level. Our study investigated the genomic characterization of eight PCa cell lines to understand which models are clinically relevant. We designed a custom AmpliSeq DNA gene panel that encompassed key molecular pathways targeting AR signaling, apoptosis, DNA damage repair, and PI3K/AKT/PTEN, in addition to tumor suppressor genes. We examined the relationship between cell line genomic alterations and therapeutic response. In addition, using DepMap's Celligner tool, we identified which preclinical models are most representative of specific prostate cancer patient populations on cBioPortal. These data will help investigators understand the genetic differences in preclinical models of PCa and determine which ones are relevant for use in their translational research.

Detection of Extracellular Vesicle-Derived RNA as Potential Prostate Cancer Biomarkers: Role of Cancer-type SLCO1B3 and ABCC3.

Extracellular vesicles (EVs) provide a minimally invasive liquid biopsy source of tumor-specific markers for patients who have already undergone prostatectomies. Our laboratory has previously demonstrated enrichment of the cancer-type solute carrier organic anion transporter family 1B3 (ct-SLCO1B3) and the ATP Binding Cassette Subfamily Member C (ABCC3) in castration-resistant cell lines (CRPC). However, their expression in EVs has yet to be explored. Our study demonstrated that ct-SLCO1B3 and ABCC3 are highly detectable in CRPC cell line-derived EVs. We also showed that ct-SLCO1B3 and ABCC3 were detectable in a CRPC xenograft mouse model, both intratumorally and in plasma-derived EVs. Our results provide evidence for EV-contained ct-SLCO1B3 and ABCC3 as novel, EV-based tumor markers for prostate cancer progression.

Targeting the metastatic niche: Single-cell lineage tracing in prime time.

Identification of actionable drug targets remains a rate-limiting step of, and one of the most prominent barriers to successful drug development for metastatic cancers. CRISPR-Cas9, a tool for making targeted genomic edits, has given rise to various novel applications that have greatly accelerated discovery in developmental biology. Recent work has coupled a CRISPR-Cas9-based lineage tracing platform with single-cell transcriptomics in the unexplored context of cancer metastasis. In this perspective, we briefly reflect on the development of these distinct technological advances and the process by which they have become integrated. We also highlight the importance of single-cell lineage tracing in oncology drug development and suggest the profound capacity of a high-resolution, computational approach to reshape cancer drug discovery by enabling identification of novel metastasis-specific drug targets and mechanisms of resistance.

Functional Drug Screening in the Era of Precision Medicine.

The focus of precision medicine is providing the right treatment to each unique patient. This scientific movement has incited monumental advances in oncology including the approval of effective, targeted agnostic therapies. Yet, precision oncology has focused largely on genomics in the treatment decision making process, and several recent clinical trials demonstrate that genomics is not the only variable to be considered. Drug screening in three dimensional (3D) models, including patient derived organoids, organs on a chip, xenografts, and 3D-bioprinted models provide a functional medicine perspective and necessary complement to genomic testing. In this review, we discuss the practicality of various 3D drug screening models and each model's ability to capture the patient's tumor microenvironment. We highlight the potential for enhancing precision medicine that personalized functional drug testing holds in combination with genomic testing and emerging mathematical models.

Single whole genome sequencing analysis blazes the trail for precision medicine.

As precision oncology evolves toward developing more targeted therapies, sequencing has moved to the forefront of treatment decision-making. Whole genome sequencing (WGS) has emerged as a technology capable of identifying candidates for rare and targeted treatments. Yet, because the tumor is constantly evolving during relapse and therapy resistance, the frequency with which WGS should be performed to identify potential new therapies for progressing patients remains unknown. A recent study in Nature Medicine by Van de Haar et al. observed a remarkably stable driver gene mutational profile among 250 biopsy pairs from 231 patients undergoing standard of care treatments during the biopsy interval. Their findings suggest that the actionable metastatic cancer genome is relatively stable over time and that a single WGS provides a complete view of the treatment opportunities available to most metastatic cancer patients.