Abstract
It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.
Highlights
Cancer is a molecular genetic disease [1,2]
If we further extend this concept at a molecular genetic level, it follows that the initiation event within these stem cells is equivalent to the sentinel mutation of vital oncogenes, and the promotion process equates to the progression of the neoplastic process as a result of the increased mutational state resulting from the dysfunctional genomic effects of such vital oncogenes
Weinstein has asked how do we identify the Achilles’ heel in specific cancers, so that each patient can be treated with the appropriate molecular targeted agent [151]? His concept of oncogene addiction states that during the multistage carcinogenesis process, cancer cells become highly dependent on specific oncogenes
Summary
Cancer is a molecular genetic disease [1,2]. it is a manifestation of the dysfunctional regulation of the normal genomic processes responsible for cell differentiation, growth, replication and cell death. A suitable molecular genetic model for cancer must provide a reasonable explanation and description of the genomic events manifested in the cancer cell, and should provide the etiological basis for genetic intratumor heterogeneity and the hallmarks of cancer [5,6] Paramount to this discussion is the crucial relevance of the seemingly inherent genetic instability of cancer and its relationship to cancer initiation and progression [7]. To establish the validity of the answers to such questions, we will need to review some pertinent information concerning carcinogenesis, certain aspects of the cancer genome, cancer cell biology and the nature of the mutations commonly found within the cancer cell This will lay the groundwork for the construction of a holistic molecular genetic model for cancer initiation and progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
