Spreading Tumor Cell (CTC)

Cancer, medically called ‘tumorigenesis’ (Thaker, Lutgendorf, & Sood, 2007, p.430) occurs when cells in the body orient themselves for malignant growth. Such cells show ‘self-sufficiency in growth signals’, are ‘insensitive to anti-growth signals’ and have ‘limitless replicative potential’ (Thaker, Lutgendorf, & Sood, 2007, p.430). Once a particular set of cells become malignant, the malignancy can spread to other set of cells in different organs due to ‘crosstalk’ between the affected cells and their surrounding ‘tissues’ and ‘micro-environments’(Thaker, Lutgendorf, & Sood, 2007, p.430).

Angiogenesis must be present for this occur, allowing cancer to spread to the blood, "thus the higher the density of new blood vessels within some tumors, the higher is the risk of metastasis of that tumor" (Mandal, 2014). Tumors have been documented to grow and spread without a direct blood supply and due to this physicians' are trying to discover ways to block tumor angiogenesis by investigating natural and synthetic inhibitors called "antiangiogenic agents" (National Cancer Institute, 2011). The goal is to slow the growth of cancer or prevent the disease entirely. According to the National Cancer Institute, "when vascular endothelial growth factor (VEGF) and other endothelial growth factors bind to their receptors on endothelial cells, signals within these cells are initiated that promote the growth and survival of new blood vessels" (2011, p. 1).

It is no secret that cancer is leading cause of death in the world. It was estimated that in 2012, 14.1 million new cases of cancer occurred worldwide and 8.2 million people died as a result of cancer [1]. Cancer prevalence is increasing at an alarming rate, yet the progress of treatment has been slow, with benefits of treatment being measured in only months or even weeks. Most patients with a specific type of cancer at a certain stage will receive the exact same form of treatment, but it has been made clear that while the treatment works well for some, it does not for a significant amount of others. The treatment that patients receive today is based on

Another biomarker that can be observed in response to cancer is ct-DNA. Ct-DNA refers to fragments of DNA from tumors found circulating in the blood stream. A recent study indicated that observing ct-DNA could have multiple useful applications for oncologists. Ct-DNA analysis during treatment could serve as an indication of how tumors react to treatment methods and whether recurrence is likely. Detecting ct-DNA in the bloodstream could even serve as an early sign of cancer, observable before imaging tests even show tumors. However, ct-DNA analysis has not yet proved to be a replacement for LDCT

Distant spread of primary malignant cells to local and distant sites was explained by several models. Cumulative research shows a pivotal role of tumor microenvironment in the process of malignant cell dissemination. This role occurs through angiogenesis and epithelial-stromal interactions, via the paracrine secretion of growth factors by stromal cells, which induce an epithelial-mesenchymal transition in neighboring epithelial cells. This result in the increased migration of epithelial cells [3].

Cancer cells migrating in the circulation are called circulating tumor cells (CTCs), which are proposed to be a promising target to interrupt distant metastatic cascades [4]. This process is likely common for all metastatic cancer cells regardless of the target organ.

Cells can enter small blood vessels and get into the bloodstream. Cancer cells that do that are called circulating tumor cells. The circulating blood sweeps up cancer cells as the blood is circulating and carries the cancer cells until they become attached

Background and Rationale. Pancreatic ductal adenocarcinoma (PDAC) is highly malignant with the lowest survival of any human cancer (1). Extensive metastasis and therapeutic resistance are the two major contributors to the dismal prognosis of this malignancy (3-5). The mechanisms by which PDAC cells can successfully spread and metastasize are largely unknown, and molecular events underlying the tumor cell’s resistance to therapeutics remain to be defined (6,7). The objective of this proposal is to use a special type of cancer cell, circulating tumor cell (CTC), responsible for the poor prognosis to characterize these cells and to test therapeutics we have designed to overcome therapeutic resistance and improve patient survival.

Bacteria accurately target tumors, actively enter tissue, simply recognized and controllably produce cytotoxicity. also, Several popular cures such as chemotherapy and radiation are poisonous for healthy tissue and not fully damage every cancer cells. Three main reasons for these difficulties are deficient tumor targeting, poor tissue invasion and insufficient toxicity to each cancer cells. These disadvantages limit qualified therapy and are linked with the rise in morbidity and mortality.

A) p53 is a protein in which it help detect damaged cells and is known

Cancer is one of the leading causes of death worldwide as it can develop in almost any organ or tissue. Significant advances in understanding the cellular basis of cancer and the underlying biological mechanisms of tumour has been vastly improved in the recent years (Jiang et al. 1994). Cancer is a genetic disease which requires a series of mutation during mitosis to develop, its characteristics can be associated with their ability to grow and divide abnormal cells uncontrollable while in the mean time invade and cause nearby blood vessels to serve its need. Even though many people are affected by cancer today, the abilities which cancer cells have make it hard to find a single effective treatment for cancer. The focus of research now lies

In the research paper, Transfer of a malignant trait to BRCA1 deficient human fibroblasts following exposure to serum of cancer patients by Dana Hamam and her colleagues, the idea of any cells within the human body that contain a single oncosuppressor mutation and can assimilate cancer factors and endure a successful malignant transformation is explored. Hamam first goes into detail about the background of cancer. A person that is diagnosed with cancer, it is usually the metastasis (the spreading) of cancer that instigates the poor healthy and possible death of the individual. Due to the statistic, Dana Hamam reviewed a piece of literature that explained the possibility of that the primary tumor cells may not be the only thing spreading throughout the body of cancer patients, but cancer cell-derived factors may also be making their way through the body as well. These cancer cell-derived factors, in theory, would create a niche that would allow malignant cancer cells to take host in other organs in the body. The factors could be numerous things such as proteins or nucleic acids that may perhaps be either floating around in the bloodstream or hitching a ride in exosomes (small extracellular membrane-enclosed vesicles). This process of trait transfers through blood circulating factors is named genometastasis. Hamam actually did an experiment on human embryonic kidney cells (HEK293) that was exposed to cancer. Those embryonic kidney cells were transformed into malignant cancer

Neovascularization is closely involved in tumor survival, progression, and spread, - factors known to contribute significantly to the difficulties in cancer treatment. Folkman (1971) presumed that survival and proliferation of cancer depend on angiogenesis, which could be a target of cancer therapy. Similar to embryos, any tumor intending to grow bigger than 2 mm, needs functional blood vessels. According to Folkman, tumors can initially grow by capturing oxygen and nutrition via diffusion from the surrounding microenvironment, but they cannot grow beyond 2 mm without angiogenesis. The mechanisms of neovascularization in tumors are complicated and each tumor shows unique features in its vasculature, depending on tissue specificity, angiogenic

Cancer has outsmarted the most brilliant amongst us ever since its discovery, and it will continue to do so until an effective treatment is found. A cure is something that is so rarely found in science, many maladies never completely leave our system. There’s almost always a mark, a trace left behind.

Therefore, patients can receive treatment before cancer metastasizes to other areas of the body, which is resulting in better health outcomes. The main challenge in circulating tumor cell (CTC) research is their detection, which requires the ability to detect one CTC out of almost 1 billion normal blood cells [2, 3]. Based on the known properties of tumor cells, several platforms for CTC detection have been developed. Such platforms can be classified into two major categories: (I) Immunochemistry-based methods, and (II) physical property-based methods. CELLSEARCHTM from Janssen Diagnostics is considered the most successful and the only FDA-approved platform for CTC detection in clinical practice in patients with breast, prostate, and colorectal cancers. Limitation of this method is the low yield of CTC capture from larger blood volume. Metastasis often involves epithelial-to-mesenchymal transition (EMT) of cells; thus, epithelial marker-dependent approaches may miss numerous CTCs that have low or absent epithelial marker expression. Isolation by size of epithelial tumor cells (ISET) [4] is another widely accepted size-based approach. This platform applies a specific membrane filter for tumor cell selection, because tumor cells are often larger and stiffer than blood cells. Main advantage of using membrane filter is that cells can be retained for further investigation. Nonetheless, the sizes of tumor cells may vary