Mode of Infection



Cancers can develop in many different types of tissues. Carcinomas are cancers that develop in endodermal or ectodermal tissues or in the epithlial lining of internal organs and glands. Sarcomas are cancers that develop in mesodermal connective tissues. Lymphomas are cancers that develop in lymphoid tissues. Leukemias are cancers that develop in lymphocytes or hematopoietic cells. Though there are many different types of cancer, there are some consistent patterns and themes to the disease.


Cancer is a state of uncontrolled cell growth. In healthy cells, cell growth is regulated by proto-oncogenes and tumor suppressor proteins. Mutations caused by a variety of factors can stimulate the development of proto-oncogenes into oncogenes and can affect the availability of tumor suppressor proteins. Mutations in proto-oncogenes can result in the constant stimulation of the cell growth pathway or the constant activation of growth receptors, even in the absence of stimulating signals. Mutations can also affect tumor supressor proteins which normally control the stimulatroy signals necessary for cell growth.


Here is a list of oncogenes and tumor supressor genes found in humans:

Oncogenes

Genes for growth factors and their receptors
PDGF Codes for platelet-derived growth factor which is involved in glioma
erb-B Codes for epidermal growth factor receptor which is involved in glioblastoma and breast cancer
erb-B2 Codes for a growth factor receptor which is involved in breast, salivary gland, and ovarian cancers
Genes for cytoplasmic relay in stimulatory signaling pathways
Ki-ras Involved in lung, ovarian, colon, and pancreatic cancers
N-ras Involved in leukemias
Genes for transcription factors that activate growth-promoting genes
c-myc Involved in leukemias and breast, stomach, and lung cancers
N-myc Involved in neuroblastoma and glioblastoma
L-myc Involved in lung cancer
Genes for other kinds of molecules
Bcl-2 Codes for a protein that normally blocks cell suicide
Bcl-1 Codes for cyclin D1, a component of the cell cycle clock
MDM2 Codes for an antagonist to the p53 tumor suppressor protein



Tumor Suppressor Genes

Cytoplasmic Protein Genes
APC Invovled in colon and stomach cancers
DPC4 Codes for relay molecule that inhibits cell division
NF-1 Codes for protein inhibitor of stimulatory (Ras) protein
NF-2 Involved in meningioma, ependymona, and schwannoma
Nuclear Protein Genes
MTS1 Codes for p16 protein, a component of the cell cycle clock
RB Codes for pRB protein, a component of the cell cycle clock
p53 Codes for p53 protein which can induce apoptosis


Together, the stimulatory and inhibitory pathways form a complex regulatory system known as the cell cycle clock. The cell cycle clock controls the progression of the cell through the various stages of growth and development. Cyclins and cyclin-dependent kinases (CDKs) are two important components of the cell cycle clock. Cyclins and CDKs are targeted by inhibitory proteins such as p15, p16, and p21. The protein p53 activates p21 and causes apoptosis (death) of malfunctioning cells. When a mutation occurs in p53, p21 cannot be activated and apoptosis cannot occur via this pathway. Nearly 50% of all human tumors contain genes that code for dysfunctional p53 proteins.



Apoptosis of a Leukemia Tumor Cell


Viruses are involved in the initiation of approximately 15% of all human cancers. Some strains of the human papilloma virus (HPV) knock out the genes coding for pRB and p53. Other viruses inject oncogenes into host cells, thereby stimulating cell growth. These viruses may have incorportated oncogenes from a previous host into their genome. Following is a list of six different viruses and the types of tumors that they cause.


Virus                    		                        Kind of

Tumor


Epstein-Barr          		                    		Burkitt's

Lymphoma, Nasopharyngeal carcinoma

Hepatitis B, C

	Hepatocellular carcinoma

HIV-1                   		                     	Karposi's

Sarcoma, B-cell Lymphomas

HTLV-1, -2          		                    		Adult

T-cell Leukemia

Human papilloma 5, 8  					        Squamous

cell carcinoma

Human papilloma 16, 18  	                                Genital

carcinomas


It is important to understand that because there are many steps involved in cancer development, there are many potential vaccine candidates. By knowing the mechanism of infection, scientists are able to focus their vaccine development efforts.




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