Mashooka Designs

for RFL American Cancer Society

One of the fundamental advances made in oncology in the last few decades is the recognition that cancer is a genetic disease. This does not mean that all cancers are inherited but neoplastic cells have an altered genetic content.
Most malignant cells have chromosomal rearrangements, and even cells with apparently normal karyotypes can almost always be found to have definable abnormalities (translocations, deletions.)
Neoplastic cells and tissues are characterized by uncontrolled growth, ususally accompanied by a loss of cellular differentation. The diseased cells and tissues are described as tumors, neoplasms, or cancers and occur in benign or malignant states. Malignant neoplastic cells typically invade surrounding tissues, violating the basement membrane of the tissue of origin and eventually undergoing metastasis.
In the US. Malignant neoplasms are responsible for causing 500,000 deaths per year, with about 1,000,000 new cases developing each year. Lung, large intestine, breast, and prostate neoplasms account for about 55% of both new cases and cancer deaths. Solid tumors arising from epithelial cells termed carcinomas, from connective or mesenchymal tissue are termed sarcomas. Malignancies that arise from the hematopoietic system include the leukemias and lymphomas. The mechanisms of malignant neoplasms are still not clear. Carcinogenesis, the creation of malignant neoplastic cells, appears to result from the activation of specific dominant growth genes, oncogenes, or a loss of functional negative effectors, tumor suppressor genes. Proto-oncogenes when activated, become oncogenes, which encode modified proteins that cuase cellular dedifferentiation and proliferation characteristics of the neoplastic state. Activation of proto-oncogenes occur by several pathways hat involve exposure of cells to chemicals, radiation or viruses. Over 100 proto-oncogenes are known to exist.
Tumor-suppressing genes in human cells, function to suppress excessive cellular growth. Retinoblastoma [tumor of the eye] is caused by genetic loss of the tumor-suppressor gene Rb.

Tumor growth represents a balance between cell division and cell death.
In addition to cells dying from necrosis, cells can exit the cell cycle by apoptosis, programmed cell death. It is believed thta all chemoherapeutic agents act via apoptosis and the apoptotic pathway is also is being targeted in the development of drugs.
The primary difficulty is that by the time cancers are detected, they are relatively large and frequently have metastasized. The chance of curing is small, local treatment as surgery and radiotherapy cannot remove or destroy all the malignant cells.
The therapy of neoplastic diseases is the removal or destruction of the neoplastic cells while minimizing toxic effects on non-neoplastic cells.

A growing number of tumor types now respond to treatment with anti-neoplastic drugs.
Because chemoherapy is a systemic treatment, it is impossible to deliver drugs to the tumor without injuring normal tissue. This can be acute or delayed [months to years after chemotherapy]. Acute side effects, nausea, vomiting are reversible. Delayed side effects are quite diverse.

Targeted therapies are becoming more and more important in treatment of cancer.
There has been more understanding of the basic science of cancer. The description of RNA and DNA tumor viruses, oncogenes, and anti-oncogenes/ tumor suppressor genes, also advances in understanding the cell-cycle regulation, apoptosis, the signaling pathways in DNA damage responses. Hopefully new agents targeted at key receptors and pathways will be more efficacious and less toxic than the classical antineoplastic agents.

[Brody's Human Pharmacology 4]