The effort to understand as to why cancer re-emerges despite treatment by chemotherapy or radiotherapy along with full surgery has revealed many new facts and theories responsible for this, the most important of all these has been the concept of cancer stem cells which lie dormant, silently & secretly, during all this period. Watching and investigating closely has revealed this not to be a straight, easy and simple task. Many processes, pathways and chemical/enzymes/hormones are involved to baffle the mind. Progression and reprogression / metastasis of cancer to other organs has lead to relevation of many new facts.

In order to simplify this difficult process, the easiest and first thing to focus is on one single aspect of this whole complicated story. We start this narrative with cancer stem cells and their microenvironment.

Our observations and derived concepts, tell us that cancer stem cells are similar to normal stem cells or progenitor cells which also have the ability for self renewal and differentiation in multiple directions to cause tumor mass production. This first step called tumor initiation occurs because of large number of mutations occurring in the DNA of the cell. Most of the times, this is helped with epigenitics and assisted by microenvironment. Microenvironment comprise many supportive factors, enzymes/hormones etc, along with inflammatory and immune cells.

Once so many mutations have taken place within the cell, the cell loses its control over cell division and acquires other malignant properties.

This conversion of a quiescent stem cell into cancer stem cell and then into active cell can take place even in non-cancer stem cell. There are many controversial views about this fact and the origin of cell is doubtful.

Nevertheless, this process of mutation continues and converts such a cell into more aggressive phenotype. This phenotype proliferates and tumor results.

The interaction of this cancer cell, the effects of chemotherapy or therapeutic intervention produce fully developed/ often resistant cancer cells.

More over, role of stemness transcription factor SOX-2 has been studied in detail. SOX-2 positively expressing cells when transplanted to mice, give rise to tumor formation. Whereas if transcription factor is deleted even from established tumors, the regression of tumor takes place.

The other important factor causing initiation of cancer is inflammation. Some of the viruses have been associated with this; viruses like HPV, hepatitis B & C, etc and helicobactor pylori. This is medicated through reactive oxygen species (ROS) reactive nitrogen species (RNS) and lipid poroxidation products (LPP). These toxic by products cause mutation in gene and through this process, initiate cancer.

Inflammation not only causes initiation of cancer under favorable conditions but it even persists through all phases of cancer development. The stem cells, the stem cells niche and the ROS, RNS and LPP all are related in cause and effect manner. The detailed mechanisms are still not clear.

The CSC niche also promotes and safeguards the progression and maintenance of stem cells in the long run via self renewal and angiogenesis. In turn, CSCs also modulate microenvironment for their survival, growth and metastasis.

The next phase in cancer development and the role of cancer stem cells comes through neoangiogenesis. As the cancer has been established, it grows and with its growth the size increase requires more food hence more circulation. This is met through neoangiogenesis. This need is fulfilled through microenvironment which produces, newer micro blood vessels. This in turn is helped by cancer stem cells; marked by surface markers CD31/ CD34, etc and endothelial cells.

These and other factors co-ordinate to secrete proangiogenic factors. The actual process involves great or details found in literature. During tumor developmental process and stem cells coordination comes the role of drug resistance.

Era’s Lucknow Medical College & Hospital Lucknow