Year: 2012
Type: book-chapter
Abstract: IntroductionPancreatic cancer remains to be one of the most lethal solid tumours of the gastrointestinal tract with a 5-year survival rate lower than 5%.It is characterised by late diagnosis, aggressive local invasion, early systemic dissemination and resistance to chemo-and radiotherapy.At the time of diagnosis more than 85% of patients have already developed metastasis and are therefore not eligible for local treatments with curative intention such as surgery or radiotherapy.Chemotherapy with Gemcitabine is the mainstay of palliative treatment with modest antitumour effects in these patients.The process of cancer initiation, progression and metastasis remains to be poorly understood.Little is known about the development of metastatic progression and the dissemination of cells from the primary tumour site into distant organs.A better understanding and thorough investigation of the biology behind pancreatic cancer invasion and metastasis is urgently needed.Current concepts and emerging fields of research in pancreatic cancer metastasis shall be discussed in this chapter. Mechanisms of metastatic evolutionMetastasis has been conventionally viewed as the last step in a cumulative process of genetic alterations within cells of a primary tumour mass.For metastatic cells to progress, they have to acquire distinct properties such as loss of cell adhesion, acquisition of an invasive potential, ability of intravasation, transport through the circulation, extravasation, formation of micro-metastases, and finally the ability to induce an angiogenic switch to form macro-metastasis (Coghlin & Murray, 2010).This hypothesis has been recently challenged by several groups (Bernards & Weinberg, 2002;Weinberg, 2008;Klein, 2008).An alternative model is proposed that considers the genetic alterations accumulated at the initial stages of www.intechopen.comPancreatic Cancer -Molecular Mechanism and Targets 62 tumour's evolution to be sufficient to promote the metastasis process.Two distinct models arising from this hypothesis are discussed in the following section. Metastasis: Progression models Late metastasis (linear progression) modelThis model is based on Leslie Fould's description of a step-wise progression of morphological abnormalities accompanying cancer (Klein, 2009).It places selection of genetic and epigenetic modifications mostly inside the established primary tumour for competitive fitness.After multiple rounds, the cells may be able to proliferate relatively autonomously at a competitive rate and seed to secondary metastatic niche sites (Fig. 1).Late disseminating cells are expected to be genetically identical to the parental cells of the primary tumour and should be subject to similar tumour cell targeting therapeutic modalities (Klein, 2008(Klein, , 2009;;Coghlin & Murray, 2010). How to referenceIn order to correctly reference this scholarly work, feel free to copy and paste the following:
Source: InTech eBooks
DOI: 10.5772/28175
Authors: Sara Chiblak, Amir Abdollahi
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G2315671612, G4815436790, G5618239459
OpenAlex ID: W1602163882