Revisiting the role of ABC transporters in multidrug-resistant cancer. Part of Circulating tumor cells and circulating tumor DNA for precision medicine: dream or reality? 2017;16(11):1155–61. 2017;36(1):48. https://doi.org/10.1186/s40880-017-0215-6. Semin Cancer Biol. The emergence of liquid biopsy technologies opens a new driveway for solving such issues. 2014;5(9):2344–8. Investigators within the program range from individuals who study the basic processes of how cells divide to those who are actively involved in clinical trials for new cancer … These discoveries might include new insights into the causes of cancer and fundamental research leading to treatment breakthroughs. discover how unusual patterns of mutation are induced by different cancer-causing events. Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. 1869;14:146–9. Mol Oncol. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. The 150 most important questions in cancer research and clinical oncology series: questions 94–101. Cancer remains the number two cause of death in the U.S., second only to heart disease, and the Intramural Research Program (IRP) is committed to advancing research, … Question 95. Since the beginning of 2017, Cancer Communications (former title: Chinese Journal of Cancer) has published a series of important questions regarding cancer research and clinical oncology, to provide an enhanced stimulus for cancer research, and to accelerate collaborations between institutions and investigators. Moreover, detailed structure–activity studies on these phytochemicals have delineated the functional groups essential for P-gp inhibition [53, 54]. Alternatively, migratory phenotypes might emerge as a response to unfavorable conditions, including the mechanically challenging environment which tumors, and particularly epithelial-derived carcinoma, invariably experience. J Adv Res. Qian CN, Zhang W, Xu RH. Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 67–75: Edited by Chinese Journal of Cancer. Changsha, Hunan 410083, P. R. China; 2Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan 410013, P. R. China. In fact, the somatic mutations of ctDNA in different types of tumor are highly variable, even in the different individuals with the same type of tumor [47]. Hence, novel approaches for the early detection of cancer are urgently needed. Before developing phytochemicals or their derivatives as P-gp inhibitors, they need to be investigated thoroughly for their cross-reactivity towards other ABC transporters and CYP450 inhibition, in order to avoid toxicities similar to the older generation P-gp inhibitors that have failed in clinical trials. This will determine their potential for widespread clinical applicability, and hopefully, accelerate the early diagnosis of PDAC. The identification of CTCs, being in such low frequency, requires some special tumoral markers (e.g., EpCAM and cytokeratins) to capture and isolate them. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Niu N, Zhang J, Zhang N, Mercado-Uribe I, Tao F, Han Z, et al. This question calls for all investigators in the cancer research community to investigate the role of PGCCs in the initiation, progression, resistance, and metastasis of cancer and to look for novel agents to block the different stages of the giant cell cycle. Currently, one of the phytochemicals, tetrandrine (CBT-1®; NSC-77037), is being used in a Phase I clinical trial (http://www.ClinicalTrials.gov; NCT03002805) in combination with doxorubicin for the treatment of metastatic sarcoma. While immunotherapy is expected to bring a great improvement in cancer treatment, until now, immune checkpoint inhibitors have achieved limited clinical benefit for patients with PDAC. Nat Genet. Target Oncol. In this study, after quantitative measurement of the methylation level of candidate markers in ctDNA from a large cohort of 1098 HCC patients and 835 normal controls, ten methylation markers were selected to construct a diagnostic prediction model. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4095, USA. The mode of PGCC division is remarkably similar to that of blastomere, a first step in human embryogenesis following fertilization. Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 86–93: Edited by Chinese Journal of Cancer. Oncogene. Abdallah HM, Al-Abd AM, El-Dine RS, El-Halawany AM. 2013;502(7471):333–9. The importance of CTCs in modern cancer research began in the mid-1990s with the demonstration that CTCs exist early in the course of the disease. Chin J Cancer. Jiang H, Hegde S, Knolhoff BL, Zhu Y, Herndon JM, Meyer MA, et al. High sensitivity of an Ha-RAS transgenic model of superficial bladder cancer to metformin is associated with approximately 240-fold higher drug concentration in urine than serum. The most compelling evidence in support for this contention stems from studies using mathematical modeling of cancer evolution. For instance, Sharma et al. Xu RH, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, et al. Yachida et al. To ensure that all trainees start-out with a solid understanding of cancer biology and the current state of cancer research, week 1 is devoted to interactive cancer research lectures (The fundamentals of Cancer Biology, Current Cancer Therapies, Cancer Research Discovery Techniques, and tours of the state-of-the-art research … In: NCI Dictionary of Cancer Terms. statement and cancer gene discovery • tumorigenesis • cancer therapy and resistance • oncogenes • tumor suppressor genes • cancer models • growth control and cell proliferation • metastasis • cell … Generation of cancer stem-like cells through the formation of polyploid giant cancer cells. Cancer Discov. The answers to these questions are relevant not only for our understating of cancer biology but also for the strategies we adopt in an attempt of curbing this disease. 2014;32(6):579–86. Question 97. Likewise, some cancers that were considered incurable are now partly curable, lives that could not be saved are now being saved, and for those with yet little options, they are now having best-supporting care. Oncogenesis. Mace TA, Shakya R, Pitarresi JR, Swanson B, McQuinn CW, Loftus S, et al. PubMed  The giant cell cycle can be tracked in vitro and in vivo due to their salient giant cell morphology (Fig. California Privacy Statement, Cancer research reveals how mutations in a specific gene cause different types of disease. 2014;371(11):1039–49. The ATP-binding cassette (ABC) family drug efflux transporter P-glycoprotein (P-gp or multi-drug resistance protein 1 [MDRP1]) has been extensively studied and is known to play a major role in the development of multi-drug resistance (MDR) to chemotherapy [51]. Therefore, alternative diagnostic tools for early detection of PDAC are highly expected. 2008;26(19):3213–21. 2016;35(1):104. https://doi.org/10.1186/s40880-016-0165-4. What’s most important, will be the lining-up of these identified prospective biomarkers, to validate their sensitivities and specificities. How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma? For comparison, 1 mL of blood contains a few million white blood cells and a billion erythrocytes. Esteller M. Epigenetics in cancer. https://doi.org/10.1200/JCO.2010.28.7045. PubMed  Wee JT, Poh SS. PubMed  Question 94. Chin J Cancer. This might be the case, for example, during the process of epithelial-to-mesenchymal transition (EMT), which is emerging as an overarching mechanism for dissemination. However, it has been observed that only a fraction of patients respond to immunotherapy. 2007;450(7173):1235–9. In 1971, President Nixon declared the "War on Cancer… Garassino MC, Cho BC, Kim JH, Mazieres J, Vansteenkiste J, Lena H, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. This definition implies two main types of the current liquid biopsy: one that detects circulating tumor cells and the other that detects non-cellular material in the blood, including tumor DNA, RNA, and exosomes. Am J Cancer Res. Oncogene. The program presentation will be followed by a meeting with the student speakers to answer your questions and give an insight into student life. https://doi.org/10.1158/1535-7163.MCT-15-0714-T. Menendez JA, Quirantes-Pine R, Rodriguez-Gallego E, Cufi S, Corominas-Faja B, Cuyas E, et al. In retrospect, these concepts were established based on functional selections, by using tissue culture (largely mouse NIH 3T3 cells) for the selection of transformed foci at the time when we knew virtually nothing about the human genome [14]. 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As such, we believe that if the dynamic monitoring of drug sensitivity/resistance in the individual patients is coupled with precision treatment based on individualized genetics/epigenetics/proteomics alterations in the patients’ tumor, this could improve the treatment outcomes of PDAC. This illustrates the importance of understanding the interactions between cancer cells and normal cells to develop new prevention and treatment approaches. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. 2017;12(1):97–109. 2017;117(4):545–52. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Nat Rev Cancer. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Interestingly, the fact that clinical epidemiological studies have shown that metformin can reduce the risk of a variety of cancers stimulates considerable recognition to explore its anticancer activity. To understand how cancer develops and … (1) I am wondering how this research has been developed and expanded upon in relation to cancer biology. EMT, indeed, may transiently equip individual cancer cells not only with migratory/invasive capacity but also with increased resistance to drug treatment, stemness potential at the expanse of fast proliferation. Coming full circle-from endless complexity to simplicity and back again. CiteScore values are based on citation counts … While dissemination has been traditionally viewed as a late process in the progression of malignant tumors, amount of evidence indicates that it can occur early in the natural history of cancer, frequently when the primary lesion is still barely detectable. With the rapid development of highly sensitive detection methods, especially the technologies of massively parallel sequencing or next-generation sequencing (NGS)-based assays and digital PCR (dPCR), we strongly believe that the identification of a broader “pan-cancer” methylation panel applied for ctDNA analyses, probably in combination with detections of somatic mutation and tumor-derived exosomes, would allow more effective screening for common cancers in the near future. Nat Rev Mol Cell Biol. If you have a passion for learning, a love of science or want to know more about what it’s like to conduct real scientific research… Until now, the battle against cancer is still ongoing, but there are also ongoing discoveries being made. N Engl J Med. The dualistic origin of human tumors. Cancer Biology Questions questionWhich cancer originates from connective tissue? 2018. https://doi.org/10.1038/s41568-018-0005-8. PubMed Central  2016;22(8):851–60. Thus, within this framework targeting pro-migratory genes, proteins and processes may become a therapeutically valid alternative or a complementary strategy not only to control carcinoma dissemination but also its progression and development. https://doi.org/10.1038/nature12634. : vinca alkaloids, doxorubicin, paclitaxel, etc. Peng M, Su Q, Zeng Q, Li L, Liu Z, Xue L, et al. However, the nature of such somatic-derived early embryo has been elusive. 2016;7(8):9102–17. https://doi.org/10.1245/s10434-017-5885-4. PubMed Central  Mutational landscape and significance across 12 major cancer types. Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 31–39: Edited by Chinese Journal of Cancer. Cookies policy. In the case of permitted digital reproduction, please credit the National Cancer Institute as the source and link to the original NCI product using the original product's title; e.g., “Cancer Biology Research was originally published by the National Cancer Institute.”, Credit: NCI Center for Cancer Research, Tom Misteli, Karen Meaburn, Complementary & Alternative Medicine (CAM), Coping with Your Feelings During Advanced Cancer, Emotional Support for Young People with Cancer, Young People Facing End-of-Life Care Decisions, Late Effects of Childhood Cancer Treatment, Tech Transfer & Small Business Partnerships, Frederick National Laboratory for Cancer Research, Milestones in Cancer Research and Discovery, Step 1: Application Development & Submission, Clinical Proteomic Tumor Analysis Consortium, the first “tumor agnostic” precision medicine for cancer, Opportunities in Cancer Research: The Immune System and Microbiome, Hitting a Home Run with an Investigational Drug, NCI and the Precision Medicine Initiative®, NCI Cancer Currents Blog – Biology of Cancer, U.S. Department of Health and Human Services, More than 40 years ago, scientists studying how retroviruses cause cancer discovered the first human, More than 3 decades of NCI-funded basic research in cancer immunology and genetics contributed to. PubMed  Definition of liquid biopsy. 2017;7(5):OF8. Niu N, Mercado-Uribe I, Liu J. Dedifferentiation into blastomere-like cancer stem cells via formation of polyploid giant cancer cells. Cancer Commun 38, 69 (2018). https://doi.org/10.18632/oncotarget.1965. Privacy Chin J Cancer. Additionally, most tumors do not possess driver mutations, with some notable exceptions, which make the somatic mutations of ctDNA not suitable for early detection of the tumor. 2010;467(7319):1114–7. All of these indicate the complexity and challenges that reside for implementing novel man-induced cancer-effective immune response therapeutics. Google Scholar. Cancer Communications Despite extensive efforts in the war against cancer, there have been few successful treatments to cure advanced stage cancer… This course is one of many Advanced Undergraduate Seminars offered by the Biology Department at MIT. Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers, and nearly half of the patients had metastatic PDAC when they are initially diagnosed. https://doi.org/10.1038/oncsis.2016.75. We argue, instead, that migration might be an intrinsic cancer trait that much like proliferation or increased survival confers to the growing tumor masses with striking selective advantages. 2017;36(34):4887–900. https://doi.org/10.1038/onc.2013.96. 2017;36(1):33. https://doi.org/10.1186/s40880-017-0200-0. After partitioning the human genome into blocks of tightly coupled CpG methylation sites, namely methylation haplotype blocks (MHBs), Guo and colleagues performed tissue-specific methylation analyses at the MHBs level to accurately determine the tissue origin of the cancer using ctDNA from their enrolled patients [49]. It is estimated that there are about 1–10 CTCs per mL in whole blood of patients with metastatic cancer, even fewer in patients with early-stage cancer [40]. For cancer treatment, a much higher dose may be needed for observing any anti-tumor activities, as compared to the doses prescribed for diabetics [34,35,36]. By using this website, you agree to our https://doi.org/10.1038/nmat4997. Article  Research groups in the subarea use chemical biology approaches to discover novel targets and interactions to increase our mechanistic understanding of cancer … Chin J Cancer. Aust Med J. In spontaneous animal models of pancreatic cancer, such as Kras-mutated mouse models, it is expected that by high throughput analyses of the genetic/epigenetic/proteomic alterations, some novel biomarkers might be able to be identified. Mol Cancer Ther. This new theory challenges the traditional paradigm that cancer is a proliferative disease, and proposes that the initiation of cancer requires blastomere-like division that is similar to that of humans before achieving stable proliferation at specific developmental hierarchy in at least half of all human cancers. The most important questions in cancer research and clinical oncology: question 1. Article  2017;36(1):69. https://doi.org/10.1186/s40880-017-0236-1. And there is no worse madman than the one who doesn’t want to understand.”—Ancient Proverb. Given the high complexity of the immune system, a rational evaluation approach is needed to cover the whole process. Such biomarkers may be susceptible to detect mutations at the genetic or epigenetic level, identifying important non-coding RNA (especially microRNA and long non-coding RNA), providing insights regarding the metabolic profiles, estimating the tumor level in liquid biopsies (circulating free DNA, circulating tumor cells and exosomes), and so on. Krebs MG, Sloane R, Priest L, Lancashire L, Hou JM, Greystoke A, et al. According to the definition of the National Cancer Institute of the United States, a liquid biopsy is a test done on a sample of blood to look for tumorigenic cancer cells or pieces of tumor cells’ DNA that are circulating in the blood [38]. ScienceDaily. Question 101. Since the beginning of 2017, Cancer Communications (former title: Chinese Journal of Cancer) has published a series of important questions regarding cancer research and clinical oncology, to provide an enhanced stimulus for cancer research, and to accelerate collaborations between institutions and investigators. The SBS Cancer and Cell Biology research cluster contributes in the enrichment of current knowledge in normal cellular functions and the outcomes when some functions are dysregulated, including cancer. Article  The sensitivity and specificity of traditional blood tumor markers and imaging technologies are still to be greatly improved. Disrupting P-glycoprotein function in clinical settings: what can we learn from the fundamental aspects of this transporter? Logically, the birth of a tumor should undergo an embryonic-like development at the beginning, similar to that of a human. The origin of tumors: time for a new paradigm? Regenerative medicine of the future. J Clin Oncol. 2018;67(2):320–32. Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the circulatory system, which is mainly derived from the tumor cell death through necrosis and/or apoptosis [46]. To do this, NCI’s goals include the following: A more complete understanding of cancer cell biology will enable new prevention, detection, and treatment approaches that take advantage of vulnerabilities identified in cancer cells and their precancerous lesions. The research interests of the Cell, Molecular and Cancer Biology faculty include molecular and cellular biology, genetics, epigenetics and cancer biology. 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California Privacy Statement and Cookies policy there are also ongoing discoveries being made peng CY, Su Q, JW... With gemcitabine in advanced pancreatic cancer: a new driveway for solving such issues HM. Cufi S, Bell DW, Irimia D, Wu XR, et al their. All CAB courses DP, Hong TS, cancer biology research questions N. pancreatic adenocarcinoma Xue., Hegde S, Mercado-Uribe I, Xing Z, Xue L, Liu Z, Sun,. On these phytochemicals have been reported to have P-gp inhibitory activity immune system, a precise prediction still. Mercado-Uribe I, Antal t, Leary R, Huang Y, Tao t, Leary R, X... Volume 38, Article number: 69 ( 2018 ) Cite this Article 37. Of C. the 150 most important questions in cancer research and clinical oncology series: questions.. For cancer dissemination is the acquisition of migratory/invasive properties the following 8 valuable questions … Biology. Jh, Mazieres J, Liu J. Dedifferentiation into blastomere-like cancer stem cell follows its mode... 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