Cancer – An Exhaustive Review of What Cancer is

Cells that can expand and propagate in an uncontrolled manner would make a tumor or a neoplasm. Having a tumor doesn’t mean it has the capability of indefinite growth, and many times a tumor doesn’t invade the surrounding healthy tissues. This is said to be benign. A tumor may become dangerous when it starts to get aggressive and progress into the surrounding healthy tissues

This kind of behavior is called malignant.  The process by which most malignant tumors spread is called metastasis, the clusters of cells break away from the original growth, then travels some distance and start propagating at the place where it gets stuck. The site of the original tumor growth is called the primary site, and the rest of the places where the dislodged cells get stuck are called secondary sites.

The cancers are classified according to their embryonic origin of the tissue:

1. Carcinomas – develop from epithelial origins like that of the gut, skin, or any lining of the glands and internal organs in the body. Some examples are Carcinoma breast, and carcinoma lung and carcinoma colon.

2. Sarcomas—these arise from mesodermal connective tissues, these tissues also give rise to bones, fats, and cartilage. They are rare and account for just 1% of cancers. Bone cancers are often seen among this category of cancers.

3. Lymphomas, Myelomas, and Leukemias—these are cancers that occur from the blood cells, the hematopoietic stem cells give rise to the mature blood cells and if any mutation of any damage to the DNA.

Lymphomas and Myelomas arise from the later stages of the development of the blood cell, it develops when the progenitor blood cells move out of the bone marrow and the cancer cells move into the circulation, they can also return to the bone marrow. Lymphomas are known to spread through the lymphatic system and then to the secondary organs of the lymphoid system. Swollen lymph nodes are the first symptom of these kinds of cancers.

 Myelomas are characterized by the proliferation of Differentiated B cells (plasma cells), they produce antibodies that are mutated. These mutated antibodies are called M proteins. They take up residence and often cause anemia and pain in the bone. Much of the symptoms are bone lesions.

Common Human Infectious Carcinogens

Infectious Agent --- Type [RNA/DNA] --- Cancer

1. HTLV1 (HUMAN T CELL LEUKEMIA VIRUS 1)       RNA TYPE       ADULT T CELL LEUKEMIA OR LYMPHOMA.

2. HPV (HUMAN PAPILOMAVIRUS)        DNA TYPE           CERVICAL CANCER.

3. EBV(EPSTEIN-BARR VIRUS)                 DNA TYPE           BURKITT’S LYMPHOMA AND NASOPHARYNGEAL CARCINOMA.

4. HHV-8           (HUMAN HERPES VIRUS-8)         DNA TYPE           KAPOSI’S SARCOMA.

5. HBV&HCV   (HEPATITIS B AND C VIRUSES)    DNA TYPE           LIVER CARCINOMA.

6. MCV(MERKEL CELL POLYOMAVIRUS) DNA TYPE           MERKEL CELL CARCINOMA (MCC).

Causes for Cancer

1. Idiopathic

2. Tobacco use

3. Tanning (excessive exposure to ultraviolet light)

4. Diet (red, processed meats)

5. Excessive Alcohol consumption

6. Unsafe sex (leading to viral infection)

7. Inflammatory conditions, such as ulcerative colitis or obesity

8. Excessive sun exposure (UV)

9. Chemical carcinogen exposure

10. High-dose chemotherapy and radiation (mainly in children being treated for existing cancers)

11. Hormonal drugs

12. Immune-suppressing drugs (taken by transplant recipients)

13. Radioactive materials, e.g., radon

Genes Associated With Cancer Control

Normally the body has a mechanism to control the growth of the cells and their proliferation in the tissues. The mechanism the body employs is cell death or apoptosis.  The genes of the body involved in maintaining the status quo of the functioning of the homeostatic process are mainly growth-regulating genes. They can normally control and destroy those cells that demonstrate out-of-control growth in the body.

1.     Tumor suppressor genes:  these genes try and suppress uncontrolled growth of the cells.

• Rb          Suppressor of retinoblastoma

• TP53      Nuclear phosphoprotein that inhibits formation of small-cell lung cancer and colon cancers

• DCC       Suppressor of colon carcinoma

• APC       Suppressor of adenomatous polyposis

• NF1        Suppressor of neurofibromatosis

• WT1      Suppressor of Wilms tumor

2.     Genes regulating apoptosis or Programmed cell death [PCD]:  these genes destroy and induce cell death in those that are mutated or have been damaged beyond repair.

• Bcl-2      Suppressor of apoptosis

• Bcl-x      Suppressor of apoptosis

• Bax        Inducer of apoptosis

• Bim        Inducer of apoptosis

• Puma    Inducer of apoptosis

3.  PROTO-ONCOGENES:  the genes that help in the uncontrolled growth of the cells.

• Sis                         A form of platelet-derived growth factor (PDGF)

• Fms                      Receptor for colony-stimulating factor 1 (CSF-1) 

• Erbb                     Receptor for epidermal growth factor (EGF)

• Neu                      Protein (HER2) related to EGF receptor 

• Erba                      Receptor for thyroid hormone

• Src                        Tyrosine kinase

• Abl                        Tyrosine kinase

• Ha-ras                  GTP-binding protein with gtpase activity

• N-ras                    GTP-binding protein with gtpase activity

• K-ras                     GTP-binding protein with gtpase activity

• Jun                        Component of transcription factor AP1

• Fos                        Component of transcription factor AP1

• Myc                      DNA-binding protein

The Cancer cell doesn’t become malignant overnight, it arises from small timid changes, one step at a time to achieve this rate of uncontrolled replication. It can be driven by somatic mutations; early genetic changes are very hard to detect. There are very few means to detect the early onset of a genetic mutation, i.e. if the genes do not show expression of a defective protein

These factors contribute to the critical initiation of malignancy. For example, If we take the adenoma, Normal epithelium may undergo loss of gene function, causing the epithelium to become a hyperproliferative epithelium, then activation of the K-ras gene or DNA hypomethylation may lead to early adenomas.

The K ras helps the proliferation and the next stage of cancer is intermediate adenoma. The loss of DCC gene function gives rise to late adenoma. Another important loss of gene function called TP53 gives rise to the actual carcinoma and then this gives rise to metastasis.

Enabling characteristics and hallmarks of cancer

1. Sustained proliferative signaling

2. Evading growth suppressors

3. Activating invasion and metastasis

4. Resisting cell death

5. Inducing Angiogenesis

6. Enabling Replicative Immortality

The Tumor Antigens

The body has markers and tumour-specific antigens or TSAs that we can assay to find out what kind of cancer we might be dealing with:

1.     Viral TSAs

•  HPV:  L1, E6,E7               Cervical carcinoma

• HBV: HBsAg                     Hepatocellular carcinoma

• SV40: Tag                          Malignant pleural mesothelioma (cancer of the lung lining)

 2. Over- expressive TSAs

• MUC1                       Breast, ovarian

• MUC13/CA              Ovarian

• 125                       Breast, melanoma, ovarian, gastric, pancreatic

• HER-2/neu               Melanoma

• MAGE                        Prostate

• PSMA                        Prostate, breast, ovarian

• TPD52                       Prostate

• PSA                            Prostate

3. Differentiation stage TSAs

•  CEA                      Colon

• gp100                   Melanoma

• AFP                       Hepatocellular carcinoma

• Tyrosinase          Melanoma

Some Cancer Prevention Tips

• Avoid using tobacco or tobacco-containing products.

• Have a healthy diet.

• Maintaining a healthy weight and BMI.

• Protection from UV radiation.

• Get vaccinated against cancer, those that are available like cervical cancer vaccine.

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