multiplication and spread of abnormal forms of the body's own cells.
The terms cancer, malignant neoplasm (neoplasm simply
means 'new growth') and malignant tumour are synonymous. Both benign and malignant tumours manifest uncontrolled proliferation, but the latter are distinguished by their capacity for dedifferentiation, their invasiveness and their ability to metastasise (spread to other parts of the body).
The appearance of these abnormal characteristics reflects
altered patterns of gene expression in the cancer cells, resulting from genetic mutations. There are three main approaches to treating established cancer- surgical excision, irradiation Chemotherapy
The relative value of each of these approaches depends on the
type of tumour and the stage of its development.
Chemotherapy may be used on its own or as an adjunct to other
forms of therapy. THE PATHOGENESIS OF CANCER Cancer cells manifest, to varying degrees, four characteristics that distinguish them from normal cells. These are uncontrolled proliferation dedifferentiation and loss of function invasiveness metastasis. THE GENESIS OF A CANCER CELL Normal cell turns into a cancer cell because of one or more mutations in its DNA, which can be acquired or inherited.
A good example is breast cancer; women who inherit a
single defective copy of either of the tumour suppressor genes BRCA1 and BRCA2 have a significantly increased risk of developing breast cancer.
However, carcinogenesis is a complex multistage process,
usually involving more than one genetic change as well as other, epigenetic factors (hormonal, cocarcinogen and tumour promoter effects, etc.) that do not themselves produce cancer but which increase the likelihood that the genetic mutation(s) will result eventually result in cancer. There are two main categories of genetic change that are important. The activation of proto-oncogenes to oncogenes. Proto-oncogenes are genes that normally control cell division, apoptosis and differentiation, but which can be converted to oncogenes that induce malignant change by viral or carcinogen action. The inactivation of tumour suppressor genes. Normal cells contain genes that have the ability to suppress malignant change-termed tumour suppressor genes (antioncogenes)-and there is now good evidence that mutations of these genes are involved in many different cancers. The loss of function of tumour suppressor genes can be the critical event in carcinogenesis. Alkylating agents and related compounds, Nitrogen mustards (Mechlorethamine , Cyclophosphamide, Ifosfamide,Melphalan (L-sarcolysin), Chlorambucil) Ethyleneimines and methylmelamines (Altretamine, Thiotepa) Methylhydrazine derivative(Procarbazine) Alkyl sulfonate(Busulfan) Nitrosoureas(Carmustine, Streptozocin (streptozotocin)) Triazenes (Dacarbazine ) Platinum coordination complexes (Cisplatin, carboplatin,oxaliplatin) antimetabolites, Folic acid analogs Methotrexate (amethopterin) Pyrimidine analogs( Fluorouracil, capecitabine, Cytarabine, Gemcitabine. Purine analogs and related inhibitors (6-mercaptopurinePentostatin) Cytotoxic antibiotics (bleomycin, Doxorubucin, Daunorubucin, idarubicin, Dactinomycin) plant derivatives (vinca alkaloids, taxanes, campothecins) Hormones (Adrenocortical suppressants, Adrenocorticosteroids, Progestins, Estrogens, Anti-estrogens, Aromatase inhibitors, Androgens, Anti-androgen, Gonadotropin-releasing hormone analog Miscellaneous agents (Tretinoin, arsenic trioxide, Imatinib, Gefitinib, erlotinib) undergoes intramolecular cyclisation, forming an unstable ethylene immonium cation (2) and releasing Cl-, the tertiary amine being transformed to a quaternary ammonium compound. The strained ring of the ethylene immonium intermediate opens to form a reactive carbonium ion (in yellow box) (3), which reacts immediately with N7 of guanine (in green circle) to give 7-alkylguanine (bond shown in blue), the N7 being converted to a quaternary ammonium nitrogen. These reactions can then be repeated with thea other Alkylation and cross-linking of DNA by -CH2mustard nitrogen CH2Cl to give a cross-link. The metabolism of cyclophosphamide. Cyclophosphamide is inactive until metabolised in the liver by P450 mixed function oxidases to 4- hydroxycyclophospha mide, which (reversibly) forms aldophosphamide. Aldophosphamide is conveyed to other tissues, where it is converted to phosphoramide mustard, the actual cytotoxic molecule, and acrolein, which is responsible for unwanted effects. The part of the cyclophosphamide molecule that gives rise to the active metabolites is shown in the blue box.