Cancer
Cancer genomics and proteomics Types of Cancer How Cancer StartsTreatment and Strategies
Links of interest: Cancer Immunome Database Cancer Research Institute Memorial Sloan-Kettering Cancer Center (see also Memorial Sloan free physician referral service at 800-525-2225 to gain access to world-renowened physicians for treamtent or a second opinion). Cancer Genome Atlas (TCGA) International Cancer Genome Consortium
American Cancer Society American Joint Committe on Cancer (AJCC) World Health Organization Clinical Trials Center for Cancer Research Clinical Trials Cancer.net (list links for finding clinical trials)
Advocacy Groups of Cancer: New Cures for Cancer
Cancer is the second leading cause of death in the United States, after heart disease. More than one million Americans are diagnosed with cancer each year, with this number likely to increase as the population ages. Cancer kills one out of six people in the developed world. Among men, the three most commonly diagnosed cancers are prostate, lung and colorectal cancer in developed countries.
Solid tumors are composed to two prinicpal structures; (1) the malignant cell itself, and supporting cells, including connective tissue and vessels that comprise the stroma, which plays a fundamental role in nutritional support and the removal of waste products for tumor cells. One type of tumor associated stromal cell is the myofibroblast which develop in the neoplastic environment as tumor cells grow and progress and play an essential role in tumor cell metastasis by stimulating angiogenesis via secretion fo stromal derived factor (SDF_-1 and by controlling the formation of the extracellular matrix via secretion of matrix metalloproteases. Cho (Gynecologic Oncology, 123 (2011) 379-386
Cancer is a class of diseases in which a group of cells display uncontrolled growth, invasion and sometimes metastasis. Cancer begins as a single cell that progresses through mutations to a malignancy. “Cancer” or “tumor” refers to any neoplastic growth in a subject. The cancer can be of the liquid or solid tumor type. Liquid tumors include tumors of hematological origin (e.g., mylomas, luekemias, lymphomas). Solid tumors can originate in organs (e.g., lungs, breasts, prostate, colon, cervix, liver). While there are over 100 distinct types of cancer, transformed malignant cells in all of the cancers can exhibit the following common properties:
- loss of anchorage dependence: whereas normal cells need to attach to surfaces in order to survive, cancerous cells can be found floating in suspension cultures
- loss of contact inhibition: whereas normal cells will arrest growth after they have filled up a defined area, malignant cells have no respect for this contact inhibition
- focus formation; in tissue cultures a single cell is transformed leading to a single cancerous colony
- genetic abnormalities such as deletions, translocations and chromosomal ploidy
- evasion of programmed cell death or apoptosis
- larger nuclear to cytoplasmic ratios
- sustained angiogeniesis through the secretion of growth factors
- Tissue invasion & metastasis of cancerous cells to other tissues
- Limitless replicative potential
- Insensitivity to anti-growth signals
- Self-sufficiency in growth signals
A neoplasm is an abnormal mass, the growth of which is purposeless, autonomous and with a tendency to be an atypical and aggressive, new growth. Oncology is the study of such neoplasms.
Challenges in Cancer Research:
The success rate for new drugs in all areas of cevelopment is dismal. Out of 5-10k chemicals that enter the drug development pipeline only one will enter the market. The failure rate for oncology drugs is even higher. See forlifeonearth.org for a list of references in the literature dealing with failure of animal models.
Development of cancer and response to anticancer drug therapy not only depends on discrete genetic alterations in the maligant clone but also on specific interactions between tumor cells and surrounding tissue components. Most established in vitro models fail to reflect the complex tissue archtiecture of an individual tumor. With respect to cancer research such as preclinical breast cancer resarch, the majority of such research is based on established cells lines. However, these cell lines frequently have undergone multiple changes influencing their biological behanior and thus no longer reflect the primary tumor of origin. Also, it is difficult to adapt the cells of many tumors to in vitro conditions when establishing a primary epithelial culture. In addition, it is most likely that separated tumor cells will behave differently in vitro, as both cell-cell and cell-matrix interactions are highly different compared to the in vivo situation (Heiko van der Kuip, BMC Cacer 2006, 6: 86, p. 2).
To investigate tumor cell behavior ex vivo it is necessary to maintain or reconstitute an environment closely resembling the tumor tissue. To simulate such conditions either three dimensional tissue cultures using several biomatrices or co-culture experiments with tumor fibroblasts have been performed. However, these sytemems can not mimic the complex tissue architecture and the high degree of variability seen in individual tumors. One possibility to maintain the tissue architecture ex vivo is the direct cultivation of fresh and intact tumor material. A problem here too is restricted diffusion of oxygen and nutrients leading to cell death in the center of the tissue cubes. This problem can be overcome by the introduction of tissue microtome establishing the prepartion of thin tissue slices. The use of confocal laser scan miroscopy based technique has also enabled one to identify cell type and test cell viability in tissue slices maintained for at least 4 days in culture (Heiko van der Kuip, BMC Cacer 2006, 6: 86, p. 2).