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== Cancer Biology Research ==

[[File:Breast-cancer-cells-article.jpg|200px|right]]
=== Why Research on Cancer Biology Is Critical to Progress against the Disease ===

Research on the biology of cancer starts with the simplest of questions: What is—and isn’t—normal?

To understand how cancer develops and progresses, researchers first need to investigate the biological differences between normal cells and cancer cells. This work focuses on the mechanisms that underlie fundamental processes such as cell growth, the transformation of normal cells to cancer cells, and the spread, or metastasis, of cancer cells.

Knowledge gained from such studies deepens our understanding of cancer and produces insights that could lead to the development of new clinical interventions. For example, studies of cell signaling pathways in normal cells and cancer cells have contributed greatly to our knowledge about the disease, revealing molecular alterations that are shared among different types of cancer and pointing to possible strategies for treatment.

The last few decades of basic research in cancer biology have created a broad base of knowledge that has been critical to progress against the disease. In fact, many advances in the prevention, diagnosis, and treatment of cancer would not have occurred without the knowledge that has come from investigating basic questions about the biology of cancer.

==Opportunities in Cancer Biology Research==

Scientists today have a growing understanding of the biology of a vast array of cancers driven by various mutations and across many body sites. New data and research approaches have created opportunities for researchers to study in detail many aspects of cancer biology, including how the normal biological programs of cell proliferation and death are altered during cancer and how the immune system responds to tumors.

The discovery of tumor stem cells in a range of cancers has created opportunities for researchers to identify these rare cells in both solid tumors and hematologic cancers, as well as to investigate the role of these cells at different stages of disease.

The recognition that the cancer cell is in a symbiotic relationship with the tumor microenvironment has created opportunities to study the interactions of cancer cells within the tumor or the host microenvironment. Researchers are now studying the molecular mechanisms and signaling pathways of cancer cell development, proliferation, and metastasis.

Researchers are also investigating the role of the human microbiome—the community of microorganisms that inhabit the human body—in the initiation and progression of tumors.

New genetic technologies developed over the past decade have helped researchers examine the functional effects of genetic alterations that underlie the development of cancer. These tools have also been used to study epigenetic changes associated with cancer, mechanisms of DNA damage and repair, and gene regulation in cancer cells.

The introduction of increasingly powerful structural biology approaches has allowed researchers to characterize the structures of mutant proteins involved in cancer, such as RAS, and other molecules in greater detail than had been possible previously. And through approaches that allow the characterization of the entire proteome, researchers are integrating genomic analysis with the analysis of the proteins in tumor cells to learn, in detail, how cancer-associated mutant proteins affect other proteins.

==Proteogenomics Research: On the Frontier of Precision Medicine==

Researchers are hopeful that proteogenomics, the integrated study of proteomics and genomics, may improve our ability to prevent, diagnose, and treat cancer at the molecular level using precision medicine.

There are also opportunities to explore cancer biology through systems biology approaches. Researchers use a variety of information and tools, such as mathematical modeling, to describe the complex interactions among components of a biological system and make predictions that help guide and further refine experimental science.

=== Challenges in Cancer Biology Research ===

Basic research in cancer biology is often viewed as “high risk,” in part because the clinical applications of a given research project might not be clear at the outset. However, knowledge gained from studying cancer cell biology not only improves our understanding of the disease but is essential for the development of clinical advances that benefit patients, as recent progress in the areas of immunotherapy and cancer vaccines illustrates.

Nonetheless, because of the uncertainty about the outcomes of basic research in cancer biology, this area of research receives relatively little funding from sources that are driven by profit. For this reason, federal funding for cancer biology research is critical.

Collaboration across disciplines is increasingly necessary to better understand key mechanisms in cancer. Therefore, some investigators may need to develop tools and strategies for sharing and communicating research results.

=== NCI's Role in Cancer Biology Research ===

NCI supports and directs research on the biological differences between normal cells and cancer cells through a variety of programs and approaches. For example, the Division of Cancer Biology (DCB) supports extramural researchers who are using a variety of methods to study cancer biology.

In addition to many of the topics mentioned above, DCB supports research on:

[[File:David-Lyden feature.jpg|200px|right]]

*the metabolism of cancer cells, the responses of cancer cells to stress, and mechanisms involved in control of the cell cycle

*biological agents (such as viruses and bacteria), host factors (such as obesity, co-morbid conditions, and age), and behaviors (such as dietary intake) that may cause or contribute to the development of cancer

*immune regulation of the development and spread of tumors and approaches to improve immune targeting and destruction of cancer cells

*genomic instability and related molecular, cytogenetic, and chromosomal effects during induction and progression to malignancy

*the role of the microenvironment created by inflammation and the inflammatory signaling molecules in the formation and progression of tumors

*processes and molecular targets where there is potential for therapeutic or preventive intervention

*the effects of hypoxia on tumor cell invasion and metastasis

*the role of somatic stem cells in determining tumor progression and metastatic behavior, and control of the stem cell niche by tumor microenvironment

NCI-supported research programs in cancer biology include the:

*'''Physical Sciences in Oncology Network (PS-ON)'''

:The goal of this initiative is to promote and foster the convergence of physical science and cancer research. Small transdisciplinary teams of physical scientists (engineers, physicists, mathematicians, chemists, and computer scientists) and cancer researchers (cancer biologists, oncologists, and pathologists) collaborate on solving problems such as determining which cell is the cell of origin for brain and hematopoietic tumors and exploring the use of three-dimensional images of single cells as cancer signatures.

*'''Cancer Systems Biology Consortium (CSBC)'''

:The CSBC focuses on combining advanced experimental approaches with mathematical and computational methodologies to build and test predictive models of cancer. The initiative takes an integrative approach to cancer research to complement and expand our current understanding of tumor development and progression across many physical and time scales, with the ultimate goal of improving the lives of cancer patients.

*'''Barrett's Esophagus Translational Research Network (BETRNet)'''

:This multidisciplinary, multi-institutional collaboration was established to better understand Barrett esophagus and to prevent esophageal adenocarcinoma. BETRNet aims to better understand esophageal adenocarcinoma (EA) biology; examine research opportunities associated with its precursor lesion, Barrett Esophagus; improve EA risk stratification and prediction; and provide strategies for EA prevention. The overriding goal is to decrease the incidence, morbidity, and mortality of this cancer.

*'''Alliance of Glycobiologists for Detection of Cancer'''

:This consortium of tumor glycomics laboratories and their research partners study the cancer-related dynamics of complex carbohydrates. This program, which NCI sponsors with the National Institute of General Medical Sciences and the National Heart, Lung and Blood Institute, aims to study the structure and function of glycans in relation to cancer.

*'''Molecular and Cellular Characterization of Screen-Detected Lesions Initiative'''

:The goal of this program is to undertake a comprehensive molecular and cellular characterization of tumor tissue, cell, and microenvironment components to distinguish screen-detected early lesions from interval and symptom-detected cancers. Researchers use various technologies and approaches to determine both the cellular and molecular phenotypes of early lesions, with the goal of better predicting the fate of early lesions.

*'''Clinical Proteomic Tumor Analysis Consortium (CPTAC)'''

:CPTAC was launched by NCI’s Office of Cancer Clinical Proteomics Research (OCCPR) to systematically identify proteins that result from genetic alterations in cancer cells, study how they affect biological processes, and provide this data with accompanying assays and protocols to the public.

*'''Applied Proteogenomics OrganizationaL Learning and Outcomes Network (APOLLO)'''

:A collaboration between the Department of Defense (DoD), Department of Veterans Affairs (VA), and NCI using the latest genomic and proteomic research methods to more rapidly and accurately identify effective drugs to treat cancer based on the proteogenomic profile of a patient’s tumor. Initial collaborative efforts will focus on a cohort of 8,000 patients with lung cancer and will make data broadly available to the research community. Eventually, the effort will be expanded to additional cancer types..

[[File:Human-Tumor-Atlas-Network-article.jpg|200px|right]]

*'''Human Tumor Atlas Network (HTAN)'''

:A collaborative network that is constructing multidimensional tumor atlases to document the molecular and cellular alterations and interactions within tumors as they develop and evolve. The atlases will represent a diverse patient population and describe the dynamics of cancer, focusing on the transition from precancer to malignancy, from local invasion to distant metastasis, and how tumors respond to treatment and develop resistance to drugs.

:NCI’s Centers of Excellence bring together intramural researchers from NCI’s Center for Cancer Research and Division of Cancer Epidemiology and Genetics to develop new projects and initiatives in various areas of cancer biology, including:

*'''Chromosome Biology'''

:The experts affiliated with this center study the mechanisms involved in chromosome function through diverse research that includes mapping the dynamic changes of the genome and transcriptome during the development of cancer and translational research for the early diagnosis of cancer.

*'''Integrative Cancer Biology and Genomics'''

:This center’s goal is to use advanced analytic technologies to define homogenous clusters of patients, who can then be treated with appropriate therapies. The researchers in this center build upon the immense amount of basic research data available in an effort to shorten the time between discovery and patient benefit by bringing together expertise in five areas: biomarkers and molecular targets, genomic approaches, human genomics and genetics, cancer inflammation, and integrative/systems biology and bioinformatics.

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