ABSTRACT
Malignancies have their etiology in malformations of DNA such as point mutations, chromosomal deletions, inversions, copy number variants (CNV), loss of heterozygocity (LOH), and other chromosomal abnormalities. However, protein biosynthesis is fundamental in all living cells because it is the mechanism that drives the cellular growth and development of all normal (healthy) and cancerous cells. For the most part, malignancies are expressing variants of protein biosynthesis due to mutations of abnormal upregulation of protein biosynthesis. Furthermore, many determinant causative proteins act in concert with hormones (growth hormone [GH], androgens, estrogens, etc.), about 20 families of growth factors and their ligands (VEGF, EGF, PDGF, IGF, etc.), which along with ample nutrients (glucose, amino acids [AAs], lipids, minerals, vitamins, etc.) constitute an important role in the control of gene expression leading to cellular growth and proliferation and/or differentiation. AAs, along with other nutrients, serve as the building blocks of protein biosynthesis as well as signal transduction messengers to transmit the nutritional status of the entire organism to individual cells. Given the critical roles AA exerts in cell survival, growth, metabolism, and signaling, it is not surprising that mammalian tumors have evolved mechanisms to adapt to protein malnutrition and related AA deprivation for short time intervals, i.e., during chemotherapy. The steady state of the cellular pool for each of the nonessential AA is the result of a balance between de novo biosynthesis plus nutrient input and utilization and removal (degradation). Diet and proteolysis provide all the essential and the majority of the nonessential AA pools. Certain key nonessential AAs like L-glutamine (Gln) and L-asparagine (Asn), which are necessary for neuronal function and survival of malignant cells, are in great demand for protein biosynthesis and as sources of carbon and nitrogen in highly proliferative conditions. Therefore, the molecular basis of gene regulation by AA is an important eld of research for study of the regulation of global protein inhibition under physiological and pharmacological conditions. However, we must leave the broad spectrum of cell survival aside, and now, we will focus on the aspects of the lymphoproliferative malignancies, which is an exciting eld in oncology.
