SIGNALING PATHWAYS AS BIOMARKERS.

Supplement Aims and Scope

This supplement is intended to focus on signalling pathways as biomarkers. Wnt-11 signalling pathway in prostate cancer, testicular cancer, and ovarian cancer are included within the supplement’s scope.

Biomarkers in Cancer aims to provide researchers working in this complex, quickly developing field with online, open access to highly relevant scholarly articles by leading international researchers. In a field where the literature is ever-expanding, researchers increasingly need access to up-to-date, high quality scholarly articles on areas of specific contemporary interest. This supplement aims to address this by presenting high-quality articles that allow readers to distinguish the signal from the noise. The editor in chief hopes that through this effort, practitioners and researchers will be aided in finding answers to some of the most complex and pressing issues of our time.

Articles should focus on signalling pathways as biomarkers and may include the following topics:

▪ Wnt-11 signalling pathway in prostate cancer

▪ Wnt-11 signaling pathways promote tumor growth

▪ Targeting signaling pathways to prevent metastases

▪ Wnt-11 expression as an indicator of tumor stage and propensity to metastasize.

▪ Testicular cancer

▪ miRNAS as biomarkers of disease

▪ Signalling pathways as indicators of histological subsets

▪ KIT and RAS signalling.

▪ Ovarian cancer

▪ Gene expression changes as prognostic indicators

▪ Cell cycle genes as prognostic factors

▪ Biomarkers of apoptosis, metastases and invasion.

At the discretion of the guest editors other articles on other relevant topics within the scope of the supplement may be included.

The main focus of this supplement is to highlight the importance of cell signaling aberrations as cancer biomarkers for early diagnosis. Further, this supplement includes the role of aberrant cellular signaling in cancer progression, resistance to cancer therapeutics and potential avenues to modulate deregulated signaling as novel therapeutic strategies.

Normal tissue carefully controls the cell signaling that instructs the cell growth and division cycle, replicative senescence, angiogenesis, apoptosis and gene expression signatures that dictate cellular identity. However, during neoplastic transformation of the cell, deregulation of cellular signaling due to oncogenic activation of growth promoting signaling intermediates and inactivation of tumor suppressors, endows cells with loss of cellular identity and relentless capacity to proliferate. Hence, the deregulated signaling pathways underlie the pathogenesis of several human malignancies.1,2 However, the identity and extent to which these signaling pathways are affected in the specific lineage of malignancy is not fully understood. Identification of signaling aberrations associated with specific types of malignancies can be utilized as cancer biomarkers and therapeutic targets.

Prior to the invention of advanced technologies such as next generation sequencing (NGS) and mass spectrometry based proteomic approaches, the diagnosis of cancer was largely dependent upon imaging analysis.3 However, now with the use of the NGS platform and proteomic screening of clinical samples, the identification of the molecular underpinning of the signaling system altered in cancer as a biomarker or therapeutic target is much appreciated.4–6 The vision to integrate independent approaches exploiting NGS, proteomic, and metabolomic platforms for the discovery of novel biomarkers of cancer through peer reviewed publications in this arena is the major goal of this journal.3 Such an integrated approach will be instrumental to contour our current model of cancer development, as well as for more efficient diagnostic and therapeutic interventions. Therefore, the identification of signaling alterations as cancer biomarkers and therapeutic targets through these approaches is the focus of this supplement. The studies presented in this supplement include utilization of multidisciplinary approaches to identify cell signaling alterations that can serve as biomarkers for specific types of cancer.

In this regard, Dr. Brown’s study published in this supplement discusses the recurrent alterations in the MAPK cell signaling pathway components FGFR2, BRAF and RAS as a biomarker for ameloblastoma, an odontogenic neoplasm. His study exploited a next generation sequencing approach to identify recurrent alterations in MAPK signaling components that can serve as potential biomarkers for ameloblastoma.7 Along with specific approaches, the accessibility of samples for investigation also play a critical role in efficient and early diagnosis of the disease. In this regard, Dr. Furtado’s study discusses the diagnosis of lung cancer through circulating cell free tumor DNA (ctDNA), which is more accessible through body fluid rather than lung biopsy and these ctDNA can serve as biomarkers for lung cancer.8 Further, in a similar line of work, along with nucleic acids, the level of secretory protein may also prove instrumental to judge the propensity of cancer progression of a particular lineage depending upon the expression level of relevant signaling biomarkers. Dr. Koizume and Dr. Miyagi highlight the role of secretory protein tissue factor (TF) and associated cellular signaling as a diagnostic biomarker in several types of cancer including ovarian cancer.9 Oncogenic signaling alterations also endow cells with resistance to anticancer therapy. Dr. Zonathan Schatz’s review on manipulation of increased oncogenic signaling to therapeutic benefit provides an insight for novel therapeutic intervention that can be designed to target cancer-sustaining and altered growth-promoting signaling that evades current therapeutic regimens.

In summary, this supplement covers the diverse spectrum of approaches that are exploited for the identification of cell signaling intermediates as biomarkers of cancer. The supplement aims to encourage potential investigators focusing on identification of altered signaling intermediates as biomarkers of cancer to contribute their studies to this journal and also to benefit from published papers that may offer novel insights into diverse approaches that can be further exploited for their studies.

Lead Guest Editor Dr. Anagh A. Sahasrabuddhe

Dr. Anagh Sahasrabuddhe received a national research fellowship from the government of India to conduct his Ph.D. at the National Center for Cell Science (NCCS) Pune, before working as a post-doctoral fellow at Northwestern University and the University of Michigan. In 2015, he was awarded the prestigious Ramanujan Fellowship to initiate an independent research program on proteolytic and epigenetic regulatory mechanisms in cancer and design of novel diagnostic and therapeutic approaches to treat cancer. He is presently working as Scientist at the Department of Biotechnology, Pandit Ravishankar Shukla University, India. His research interests include studies on the inappropriate gain or loss of components of molecular machine that maintain and operate chromatin structure/function and their association with disease progression using genetic, epigenetic and proteomic approaches. His studies also include the identification of cancer biomarkers and therapeutic targets for several lineages of hematologic malignancies through next generation sequencing approaches. His seminal contribution to cancer research is documented in more than 20 peer reviewed scientific journals and two US Patents. He also serves as a reviewer for more than 10 peer reviewed international journals and as an editorial board member of a few of them.

anagh@umich.edu

anaghanant@gmail.com

Guest Editors

DELPHINE C.M. ROLLAND

Dr. Delphine Rolland obtained her PharmD degree from the Institut des Sciences Pharmaceutiques et Biologiques, University Claude Bernard Lyon I, Lyon, France, where she specialized in hematology. Later on, she worked on the characterization of mass spectrometry-based proteomic signatures of B-cell lymphomas and obtained her PhD degree from the University Claude Bernard Lyon I, Lyon, France. She served as a clinical assistant professor of hematology at the Medical School of the University Joseph Fournier, Grenoble, France. Dr. Delphine Rolland joined the University of Michigan, Ann Arbor, MI, USA, for a post-doctoral position where she developed a particular interest in mass spectrometry-based characterization of protein post-translational modifications of lymphomas in order to identify novel biomarkers as well as novel therapeutic targets. In 2015, Dr. Delphine Rolland moved to the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Her contribution to cancer research is documented in more than 20 peer reviewed scientific journals and 4 US patents.

drolland@upenn.edu

PINAKI P. BANERJEE

Dr. Pinaki P. Banerjee obtained his PhD degree from the National Center for Cell Science, Pune, India, in defining a novel role of a tumor rejection antigen, GP96, in primary T cell activation. Later Dr. Banerjee worked on chondrosarcoma, prostate cancer and fibrosarcoma models and on a concept to develop a universal cancer vaccine. Dr. Banerjee was an Assistant Professor of Pediatrics at Baylor College of Medicine where he studied the outcome of human effector cell and target cell interaction in health and disease conditions. This includes effector function of human natural killer cells against tumorigenic cells. His areas of research also included the role of human innate and adaptive immune cells in inflammatory diseases, and viral infections that modulate innate immune function. His “bench to bedside” ongoing research on primary immunodeficiency clarifies the success of implying IL-2 or gene therapy as a treatment for patients with Wiskott Aldrich Syndrome, which leads to autoimmune diseases and cancer. Currently he is the Director of Immunology and Project Management of Kiromic Biopharma, a clinical stage biopharmaceutical company that is focused in developing therapeutics for cancer. Areas of his present research include the role of human innate and adaptive immune cells in cancer therapy, development of biomarkers for cancer, and studying signaling pathways of various drugs to prevent the progression of cancer.

Dr. Banerjee has 31 peer reviewed publications and serves on editorial boards and as a reviewer for various peer-reviewed journals.