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Precision Medicine In Cancer

Winter Spence
Prostate cancer continues to be the most commonly diagnosed cancer among Canadian men. The introduction of routine screening and advanced treatment options have allowed for a decrease in prostate cancer-related mortality, but outcomes following treatment continue to vary widely. In addition, the overtreatment of indolent prostate cancers causes unnecessary treatment toxicities and burdens health care systems. Accurate identification of patients who should undergo aggressive treatment, and those which should be managed more conservatively, needs to be implemented...
December 2018: Journal of Medical Imaging and Radiation Sciences
William T Tran, Charmaine Childs, Heidi Probst, Golnaz Farhat, Gregory J Czarnota
Guidelines from the American National Comprehensive Cancer Network recommend neoadjuvant chemotherapy to patients with locally advanced breast cancer (LABC) to downstage tumours before surgery. However, only a small fraction (15%-17%) of LABC patients achieve pathological complete response (pCR); that is, no residual tumour in the breast, after treatment. Measuring tumour response during neoadjuvant chemotherapy can potentially help physicians adapt treatment, thus potentially improving the pCR rate. Recently, imaging biomarkers that are used to measure the tumour's functional and biological features have been studied as pretreatment markers for pCR or as an indicator for intratreatment tumour response...
December 2018: Journal of Medical Imaging and Radiation Sciences
Ya-Ping Ye, Hong-Li Jiao, Shu-Yang Wang, Zhi-Yuan Xiao, Dan Zhang, Jun-Feng Qiu, Ling-Jie Zhang, Ya-Li Zhao, Ting-Ting Li, Li-Liang, Wen-Ting Liao, Yan-Qing Ding
BACKGROUND: Colorectal cancer (CRC) is one of the most common digestive malignant tumors, and DMTN is a transcriptionally differentially expressed gene that was identified using CRC mRNA sequencing data from The Cancer Genome Atlas (TCGA). Our preliminary work suggested that the expression of DMTN was downregulated in CRC, and the Rac1 signaling pathway was significantly enriched in CRC tissues with low DMTN expression. However, the specific functions and underlying molecular mechanisms of DMTN in the progression of CRC and the upstream factors regulating the downregulation of the gene remain unclear...
December 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
Prithy C Martis, Atira T Dudley, Melissa A Bemrose, Hunter L Gazda, Barry H Smith, Lawrence S Gazda
BACKGROUND: Agarose encapsulated murine renal adenocarcinoma cells (RENCA macrobeads) are currently being investigated in clinical trials as a treatment for therapy-resistant metastatic colorectal cancer. We have previously demonstrated the capacity of RENCA macrobeads to produce diffusible substances that markedly inhibit the proliferation of epithelial-derived tumor cells outside the macrobead environment. This study examined the molecular mechanisms underlying the observed inhibition in targeted tumor cells exposed to RENCA macrobeads...
December 4, 2018: BMC Cancer
Michael H Gerber, Patrick W Underwood, Sarah M Judge, Daniel Delitto, Andrea E Delitto, Rachel L Nosacka, Bayli B DiVita, Ryan M Thomas, Jennifer B Permuth, Steven J Hughes, Shannon M Wallet, Andrew R Judge, Jose G Trevino
Cancer cachexia is a debilitating condition seen frequently in patients with pancreatic ductal adenocarcinoma (PDAC). The underlying mechanisms driving cancer cachexia are not fully understood but are related, at least in part, to the immune response to the tumor both locally and systemically. We hypothesize that there are unique differences in cytokine levels in the tumor microenvironment and systemic circulation between PDAC tumors and that these varying profiles affect the degree of cancer cachexia observed...
December 1, 2018: International Journal of Molecular Sciences
Zheng Hu, Ding Ma
Cervical cancer is a complex disease caused by both genetic susceptibility and environmental factors. Inherited genomic variance, high-risk human papilloma virus (HPV) infection/integration, genome methylation and somatic mutation could all constitute one machine learning model, laying the ground for molecular classification and the precision medicine of cervical cancer. Therefore, for cervical screening, next generation sequencing (NGS)-based HPV DNA and other molecular tests as well as dynamic machine learning models would accurately predict patients with potential to develop the cancer, thereby reducing the burden of repeated screening...
February 25, 2018: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
Gaurav Goel
Colorectal cancer (CRC) is a major public health problem, both in the USA and globally. Over the past 20 years, significant advances have been made in the treatment of patients with metastatic CRC (mCRC). Recent efforts in the field of biomarkers have focused on the development of molecular diagnostics to define the subset of patients with mCRC that is likely to derive most benefit from anti-EGFR therapy. Herein, we review the recent advancements in molecular stratification of CRC and the role of current as well as emerging biomarkers in this disease...
2018: Cancer Management and Research
Sneha P Couvillion, Ying Zhu, Gabe Nagy, Joshua N Adkins, Charles Ansong, Ryan S Renslow, Paul D Piehowski, Yehia M Ibrahim, Ryan T Kelly, Thomas O Metz
Mass-spectrometry based omics technologies - namely proteomics, metabolomics and lipidomics - have enabled the molecular level systems biology investigation of organisms in unprecedented detail. There has been increasing interest for gaining a thorough, functional understanding of the biological consequences associated with cellular heterogeneity in a wide variety of research areas such as developmental biology, precision medicine, cancer research and microbiome science. Recent advances in mass spectrometry (MS) instrumentation and sample handling strategies are quickly making comprehensive omics analyses of single cells feasible, but key breakthroughs are still required to push through remaining bottlenecks...
December 3, 2018: Analyst
Boris Winterhoff, Shobhana Talukdar, Zenas Chang, Jinhua Wang, Timothy K Starr
PURPOSE OF REVIEW: This article discusses the advances, applications and challenges of using single-cell RNA sequencing data in guiding treatment decisions for ovarian cancer. RECENT FINDINGS: Genetic heterogeneity is a hallmark of ovarian cancer biology and underlies treatment resistance. Defining the different cell types present within a single ovarian cancer is difficult, but could ultimately lead to improvements in diagnosis and treatment. Next-generation sequencing technologies have rapidly increased our understanding of the molecular landscape of epithelial ovarian cancers, but the majority of these studies are conducted on bulk samples, resulting in data that represents an 'average' of all cells present...
November 30, 2018: Current Opinion in Obstetrics & Gynecology
Brian Olson, Akash Patnaik
The last two decades of cancer research have seen two major advancements in our ability to treat cancer: precision medicine and immunotherapy. While these approaches have shown striking anticancer efficacy in numerous malignancies, they have not shown similar success and applicability in advanced prostate cancer patients. The fields of precision medicine and immunotherapy have come to realize that targeted therapies are capable of not only inhibiting tumor cell growth, but also promoting antitumor immunity by modulating the tumor microenvironment...
November 29, 2018: Urologic Oncology
Asunción Díaz-Serrano, Ana Sánchez-Torre, Luis Paz-Ares
Personalized patient-precise medicine is being gradually incorporated into clinical practice for the treatment of non-small-cell lung cancer (NSCLC). The EGFR pathway has been explored as a druggable target with monoclonal antibodies such as cetuximab or necitumumab. Necitumumab is a humanized IgG1 anti-EGFR. In the Phase III SQUIRE trial, necitumumab used as first-line therapy in combination with cisplatin and gemcitabine showed a reduction in risk-of-death and a better disease control rate in advanced squamous NSCLC...
December 3, 2018: Future Oncology
Saif S Ahmad, Marka R Crittenden, Phuoc T Tran, Paul G Kluetz, Gideon M Blumenthal, Helen Bulbeck, Richard D Baird, Kaye J Williams, Timothy Illidge, Stephen Hahn, Theodore S Lawrence, Patricia A Spears, Amanda J Walker, Ricky A Sharma
Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumour, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs, however this ambition remains to be realised. In view of this lack of progress, the FDA-AACR-ASTRO Clinical Development of Drug-Radiotherapy Combinations Workshop was held in February 2018 to bring together stakeholders and opinion leaders from academia, clinical radiation oncology, industry, patient advocacy groups and the FDA in order to discuss challenges to introducing new drug-radiotherapy combinations to the clinic...
November 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ricardo Leão, Ardalan E Ahmad, Robert J Hamilton
Testicular germ cell tumors (TGCTs) represent the most common solid tumors among men aged 15 to 34 years. Fortunately, recent advances have made testicular cancer a highly curable disease. Despite the high cure rates, there are still several areas in testis cancer care where treatment decisions are controversial and guided only with clinical factors and historic serum tumor markers. Unfortunately, unlike other genitourinary malignancies, modern research techniques have not been widely tested or applied to germ cell tumors, perhaps as a result of excellent prognosis in this cohort of young men...
October 23, 2018: Clinical Genitourinary Cancer
Jake R Conway, Eric Kofman, Shirley S Mo, Haitham Elmarakeby, Eliezer Van Allen
Immune checkpoint blockade (ICB) therapies, which potentiate the body's natural immune response against tumor cells, have shown immense promise in the treatment of various cancers. Currently, tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are the primary biomarkers evaluated for clinical management of cancer patients across histologies. However, the wide range of responses has demonstrated that the specific molecular and genetic characteristics of each patient's tumor and immune system must be considered to maximize treatment efficacy...
November 29, 2018: Genome Medicine
Andrew McGuigan, Paul Kelly, Richard C Turkington, Claire Jones, Helen G Coleman, R Stephen McCain
This review aims to outline the most up-to-date knowledge of pancreatic adenocarcinoma risk, diagnostics, treatment and outcomes, while identifying gaps that aim to stimulate further research in this understudied malignancy. Pancreatic adenocarcinoma is a lethal condition with a rising incidence, predicted to become the second leading cause of cancer death in some regions. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients...
November 21, 2018: World Journal of Gastroenterology: WJG
Darko Castven, Diana Becker, Carolin Czauderna, Diana Wilhelm, Jesper B Andersen, Susanne Strand, Monika Hartmann, Stefanie Heilmann-Heimbach, Wilfried Roth, Nils Hartmann, Beate K Straub, Friederike L Mahn, Sophia Franck, Sharon Pereira, Anna Haupts, Arndt Vogel, Marcus A Wörns, Arndt Weinmann, Stefan Heinrich, Hauke Lang, Snorri S Thorgeirsson, Peter R Galle, Jens U Marquardt
Primary liver cancer (PLC) ranks among the most lethal solid cancers worldwide due to lack of effective biomarkers for early detection and limited treatment options in advanced stages. Development of primary culture models that closely recapitulate phenotypic and molecular diversities of PLC is urgently needed to improve the patient outcome. Long-term cultures of 7 primary liver cancer cell lines of hepatocellular and cholangiocellular origin were established using defined culture conditions. Morphological and histological characteristics of obtained cell lines and xenograft tumors were analyzed and compared to original tumors...
November 28, 2018: International Journal of Cancer. Journal International du Cancer
Shijie Sheng, M Margarida Bernardo, Sijana H Dzinic, Kang Chen, Elisabeth I Heath, Wael A Sakr
The predominant cause of cancer mortality is metastasis. The major impediment to cancer cure is the intrinsic or acquired resistance to currently available therapies. Cancer is heterogeneous at the genetic, epigenetic, and metabolic levels. And, while a molecular-targeted drug may be pathway-precise, it can still fail to achieve wholesome cancer-precise toxicity. In the current review, we discuss the strategic differences between targeting the strengths of cancer cells in phenotypic plasticity and heterogeneity and targeting shared vulnerabilities of cancer cells such as the compromised integrity of membranous organelles...
November 27, 2018: Cancer Metastasis Reviews
Gholamreza Bidkhori, Rui Benfeitas, Martina Klevstig, Cheng Zhang, Jens Nielsen, Mathias Uhlen, Jan Boren, Adil Mardinoglu
Hepatocellular carcinoma (HCC) is one of the most frequent forms of liver cancer, and effective treatment methods are limited due to tumor heterogeneity. There is a great need for comprehensive approaches to stratify HCC patients, gain biological insights into subtypes, and ultimately identify effective therapeutic targets. We stratified HCC patients and characterized each subtype using transcriptomics data, genome-scale metabolic networks and network topology/controllability analysis. This comprehensive systems-level analysis identified three distinct subtypes with substantial differences in metabolic and signaling pathways reflecting at genomic, transcriptomic, and proteomic levels...
November 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
Tomer Cooks, Sofia Dp Theodorou, Eleni Paparouna, Sophia V Rizou, Vassilios Myrianthopoulos, Vassilis G Gorgoulis, Ioannis S Pateras
In the era of precision medicine immunohistochemistry (IHC) and immunocytochemistry (ICC) share some of the highlights in personalized treatment. Survival data obtained from clinical trials shape the cut-offs and IHC scoring that serve as recommendations for patient selection both for targeted and conventional therapies. Assessment of Estrogen and Progesterone Receptors along with HER2 status has been among the first approved immunostaining assays revolutionizing breast cancer treatment. Similarly, ALK positivity predicts the efficacy of ALK inhibitors in patients with non-small cell lung cancer (NSCLC)...
November 27, 2018: Histology and Histopathology
James D Chambers, Elle F Pope, Colby L Wilkinson, Peter J Neumann
BACKGROUND: FDA-required labeling summarizes certain data that the FDA relies on in its drug approval process. However, when determining coverage of specialty drugs, health care payers may consider dissimilar evidence. OBJECTIVE: To compare evidence cited by the largest U.S. commercial payers in their specialty drug coverage policies with evidence featured in the labeling of the indicated drugs. METHODS: We used the Tufts Medical Center Specialty Drug Evidence and Coverage Database (SPEC)-a database of specialty drug coverage policies issued by 17 of the 20 largest U...
December 2018: Journal of Managed Care & Specialty Pharmacy
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