Hallmarks of Cancer Biology
Added on 2021-04-16
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Running head: HALLMARKS OF CANCER BIOLOGYIdentifying Hallmarks of Cancer Biology with a detailed insight of Sustaining ProliferativeThinking and Resisting Cell DeathName of the StudentName of the UniversityAuthor Note
1HALLMARKS OF CANCER BIOLOGYMetastatic cancer is a type of cancer in which cancer cells transfer to different organsin contrast to the site where it was first formed. The other part of the body in which it formsthe new tumor is called as metastatic tumors. Metastatic of cancer takes place in a complexsystem of heterogeneous cell population. One of the hallmarks of metastatic cancer is theinvasion of cell from local areas to distance tissues. There are many other mechanismunderlying development of metastatic cancer such as sustaining proliferative signaling,evading growth suppressors, overcoming immune destruction, tumor promotinginflammation, invasion, angiogenesis, mutation, resisting cell death and deregulationenergetic (1). This essay gives more insight into each hallmark of cancer and its contributionto cancer development. Furthermore, the essay also discusses in more detail about thehallmarks of sustaining proliferative signaling and resisting cell death and the role of specificchemotherapy drugs targeting these hallmarks. Hallmarks of cancer development:The 10 hallmarks underlying metastatic cancer development and their role inmetastatic dissemination are as follows:1.Sustaining proliferative signaling: The most fundamental mechanism for cancer celldevelopment is their ability to proliferate constantly. Compared to normal cells,cancer cells deregulate the growth promoting signals resulting in unlimited growth asthey are no more dependent on proliferation signals. Tumor cells acquire the propertyto sustain proliferative signaling by producing their own growth factors causingautocrine stimulation. The production of paracrine signal also enhances growth ofnormal cells. In addition, their reliance on growth factors are reduced by theconstitutive activation of downstream signaling pathways (2). The downstreamsignaling pathway is activated by somatic mutations in the catalytic subunit of
2HALLMARKS OF CANCER BIOLOGYphosphoinositide 3-kinase (PI3-kinase) (3). This indicates the mechanism by whichcancerous cell grow and develop. 2.Evading growth suppressors- Evading growth suppressors is that hallmarks of cancercells that complements the process of sustaining proliferative signaling. The ability toevade growth suppression is a necessary process to sustain growth signal as thismechanism acts to prevent all those pathways that negatively influence cellproliferation.TP53 and RB are some tumor suppressive protein coding gene involvesin inhibiting cell growth and mutation or deletion of these genes results inthedevelopments of cancerous tumors in patient (3). Another mechanism by whichcancer cells inhibits the function of tumor suppressor genes includes interaction of thencRNA fragments with tumor suppressor proteins. This results in release of highlevels of PSF-binding RNAs from tumor cell line (4). Hence, role of ncRNAs inevading growth suppressors gives clear insight into mechanism behind cancerdevelopment. 3.Avoiding immune destruction: Immune evasion or avoiding immune destruction isalso one of the hallmarks of cancer development. This process also acts as a majorbarrier in designing anti-cancer therapeutic strategies. The evasion of immune attackoccurs by creating an immune suppressive environment by means of tumor variantsresistant to immune effectors. Cytotoxic T cells and CD4+ and T helper cells produceinterferon and cytotoxin to inhibit the development of cancer cells, however theprocess of chronic inflammation counteracts immune response and promotes cancerdevelopment. The tumor cells also exploit regulatory T cells (Tregs), defectiveantigen presentation and immune suppressive mediators and apaptosis mechanism toevade immune response. In the case of cancer metastasis also, the mechanism of
3HALLMARKS OF CANCER BIOLOGYdetaching from primary tumor and travelling through the surroundings tissues occursby avoiding immune destruction (5). 4.Enabling replicative immortality: Enabling replicative immortality is the third trait ofcancer which indicates the potential of cancer cells towards unlimited replication.Normal cells cannot pass through large number of cell division cycles; however tumorcells possess the potential to unlimited replication. Tumor cells possess unlimitedreplication potential by way of circumventing the loss of telomeres that determinesthe number of cell division cycles. Tumor cells are able to control the loss oftelomeres by the expression of telomerase enzyme and the activation of telomeretandem lengthening pathway. Long ncRNAs also plays a role in replicativeimmortality as it acts as the regulator of genome stability and replication (3). 5.Tumor promoting inflammation: In the process of cancer development, it has beenfound that the negative effect of the immune system results in cancer development.The presence of white blood cells in tumor cells gives indication of the relationbetween inflammation and cancer development. The complex interplay betweenimmunity and inflammation causes the development of cancer cells. Tumorpromoting inflammation (TAM) and anti-tumor immunity regulates the pathway forformation of tumor. Tumor associated macrophases also provides the environment fortumor growth, invasion and metastasis (6). From this evidence, it can be said thatTAM cells plays a major role in tumor promoting inflammation and cancerdevelopment. This knowledge can be effectively utilized to design cancer treatmentoptions. 6.Activating invasion and metastasis: Another mechanism that is regarded as a hallmarkof cancer includes their ability to invade and form distant metastases. The steptowards invasion and metastatis initiates when morphological changes occur in cancer
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