Review of precision cancer medicine: Evolution of the treatment paradigm.

In recent years, biotechnological breakthroughs have led to identification of complex and unique biologic features associated with carcinogenesis. Tumor and cell-free DNA profiling, immune markers, and proteomic and RNA analyses are used to identify these characteristics for optimization of anticancer therapy in individual patients. Consequently, clinical trials have evolved, shifting from tumor type-centered to gene-directed, histology-agnostic, with innovative adaptive design tailored to biomarker profiling with the goal to improve treatment outcomes. A plethora of precision medicine trials have been conducted. The majority of these trials demonstrated that matched therapy is associated with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To improve the implementation of precision medicine, this approach should be used early in the course of the disease, and patients should have complete tumor profiling and access to effective matched therapy. To overcome the complexity of tumor biology, clinical trials with combinations of gene-targeted therapy with immune-targeted approaches (e.g., checkpoint blockade, personalized vaccines and/or chimeric antigen receptor T-cells), hormonal therapy, chemotherapy and/or novel agents should be considered. These studies should target dynamic changes in tumor biologic abnormalities, eliminating minimal residual disease, and eradicating significant subclones that confer resistance to treatment. Mining and expansion of real-world data, facilitated by the use of advanced computer data processing capabilities, may contribute to validation of information to predict new applications for medicines. In this review, we summarize the clinical trials and discuss challenges and opportunities to accelerate the implementation of precision oncology

Outlook Magazine, Winter 2018

https://digitalcommons.wustl.edu/outlook/1206/thumbnail.jp

Clinical proteomics for precision medicine: the bladder cancer case

Precision medicine can improve patient management by guiding therapeutic decision based on molecular characteristics. The concept has been extensively addressed through the application of –omics based approaches. Proteomics attract high interest, as proteins reflect a “real-time” dynamic molecular phenotype. Focusing on proteomics applications for personalized medicine, a literature search was conducted to cover: a) disease prevention, b) monitoring/ prediction of treatment response, c) stratification to guide intervention and d) identification of drug targets. The review indicates the potential of proteomics for personalized medicine by also highlighting multiple challenges to be addressed prior to actual implementation. In oncology, particularly bladder cancer, application of precision medicine appears especially promising. The high heterogeneity and recurrence rates together with the limited treatment options, suggests that earlier and more efficient intervention, continuous monitoring and the development of alternative therapies could be accomplished by applying proteomics-guided personalized approaches. This notion is backed by studies presenting biomarkers that are of value in patient stratification and prognosis, and by recent studies demonstrating the identification of promising therapeutic targets. Herein, we aim to present an approach whereby combining the knowledge on biomarkers and therapeutic targets in bladder cancer could serve as basis towards proteomics- guided personalized patient management

Frontiers in Pigment Cell and Melanoma Research

We identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology. Significantly, this document encapsulates important advances in melanocyte and melanoma research including emerging frontiers in melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo, albinism, genomics and systems biology, epidemiology, pigment biophysics and chemistry, and evolution

Addressing current challenges in cancer immunotherapy with mathematical and computational modeling

The goal of cancer immunotherapy is to boost a patient's immune response to a tumor. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumor microenvironment, immune-modulating effects of conventional treatments, and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modeling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumor classification, optimal treatment scheduling, and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modelers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumor-immune biology. We conclude the review with recommendations for modelers both with respect to methodology and biological direction that might help keep modelers at the forefront of cancer immunotherapy development.Comment: Accepted for publication in the Journal of the Royal Society Interfac