What is Androgen Dependent Versus Androgen Independent Prostate Cancer – 2

Androgen independent prostate cancer

Pathways by which androgen-independence is initiated in prostate cancer cells. Pic courtesy: http://www.nature.com/nrc/journal/v1/n1/fig_tab/nrc1001-034a_F2.html

What triggers the rise of androgen independent prostate cancer (AIPC)? As we have seen in part 1 of this blog, tumor cells are androgen dependent in the initial stages. After treatment with androgen ablation therapies, there is usually, an initial response but cancer progresses to give rise to tumor cells that are androgen independent. Genetic modifications are definitely one of the main factors responsible for androgen independence. Evidence indicates that androgen receptors (AR) aid in proliferation of androgen-independent prostate cancer cells. The malignant cells go on to develop different signaling pathways that manages to sabotage and avoid therapeutic attempts made for controlling cancer cells.

Emergence of Androgen Independence in Prostate Cancer Cells

Prostate cancer has been observed to proceed to a stage where tumor cells no longer depend on androgens for growth or survival. Androgen independence of a cancerous cell leads to failure of androgen ablation therapy. The phenomenon of androgen independence has been associated with mutations in the ligand binding capacity of the AR. Some of the pathways that these cancerous cells follow for survival, proliferation, and regulation include,

  • gene amplification leading to increased production of AR
  • AR displaying increased sensitivity to androgens
  • there is an increase in conversion of testosterone to dihydrotestosterone (DHT)
  • AR activation by non-androgenic molecules present in circulation
  • formation of ligand independent- AR
  • presence of subpopulation of androgen-independent cancer cells even before initiation of androgen ablation treatment.

These are definitely not the only pathways adopted by the tumor cells, and further research would positively reveal more pathways. More than one of the mentioned pathways can be adopted by a single cancer for progression to AIPC.

Successful treatment might require a personalized analysis of the type of AIPC targeted. Each patient’s cancer would have to be studied and analyzed so that the treatment can be more target specific. Ideal and effective treatment would save the cells from AIPC mechanisms and restore normal growth and regulation cycle. Fresh diagnostic measures are underway to thwart unregulated prostate cancer cell growth.

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