Drugs and cancer





The term cancer refers to a malignant tumour. Cancer cells can manifest, in greater or lesser degree, uncontrolled proliferation, invasiveness, the ability to metastasize and/or infiltrate normal tissues and loss of function due to lack of the capacity to differentiate. Benign tumours manifest only uncontrolled proliferation.


Pathology


The two main alterations in DNA underlying cancerous change in a cell are (1) mutation/inactivation of tumour suppressor genes and (2) mutation/activation of proto-oncogenes . Proto-oncogenes are genes that normally code for the growth factor-induced and apoptotic pathways, and thus control the cell cycle and cell proliferation. Oncogenes code for cancerous changes. The development of cancer, however, is a multistage process, involving not only more than one genetic change, but also other non-genetic factors (hormonal effects, presence of carcinogens) that increase the likelihood that the mutation(s) will result in cancer. The formation of new blood vessels (angiogenesis) is required for the growth of the tumour, the infiltration of cancer cells into nearby tissue and their metastasis to other organs.


Most anticancer drugs are cytotoxic, i.e. they damage or kill cells; they do not affect the underlying pathogenetic mechanisms, namely the changes in growth factors and/or their receptors, in the cell cycle and apoptotic pathways, in telomerase expression or in tumour-related angiogenesis. Most are mainly antiproliferative, acting primarily on dividing cells ( Fig. 33.1 ) and have no specific inhibitory effect on invasiveness, the loss of differentiation or the tendency to metastasize. As these cytotoxic drugs inhibit cell proliferation, they will also affect rapidly dividing normal cells. Therefore they can depress the bone marrow, impair healing, depress growth, cause sterility and hair loss and be teratogenic; most cause nausea and vomiting and detrimental effects on the mucous lining of the gastrointestinal (GI) tract.




Fig. 33.1


Sites of action of some anticancer agents that act on dividing cells.

DTMP , 2-Deoxythymidylate.


There are also now many new immunotherapeutic approaches to the treatment of cancers that use the body’s own immune system to attack cancer cells. Other new approaches include targeting receptor mechanisms upregulated in cancer cells and targeting these with biologics ( Table 33.1 ).



Table 33.1

Summary of Cancer Therapies

From Page C. Crash Course: Pharmacology. 5th ed. Philadelphia: Elsevier; 2019.












































































Class of drug Drug Mechanism of action Use Important side effects
Alkylating agent Cyclophosphamide Pronounced effect on lymphocytes Immunosuppressant Intrastrand cross-linking of DNA Haematological malignancy N&V
Bone marrow depression
Haemorrhagic cystitis
Alkylating agent Procarbazine Inhibits DNA and RNA synthesis
Interferes with mitosis
Hodgkin’s disease Hypertension
Flushing reaction
Platinum compound Cisplatin Intrastrand cross-linking of DNA Solid tumours (especially testes and ovary) Nephrotoxic
Severe N&V
Antimetabolite Fluorouracil Inhibition of DNA synthesis Basal cell carcinoma Gastrointestinal upset
Myelotoxicity
Antimetabolite Cytarabine Pyrimidine analogue—inhibits DNA polymerase Acute myeloid leukaemia Gastrointestinal upset
Myelotoxicity
Cytotoxic antibiotic Doxorubicin Inhibits DNA and RNA synthesis, through interference with topoisomerase II Bladder cancer N&V
Myelosuppression
Hair loss
Cardiotoxic in high doses
Vinca alkaloids (mitotic inhibitor) Vincristine Bind to tubulin and inhibit its polymerization, causing arrest at metaphase inhibiting mitosis Haematological malignancy Mild myelosuppression
Neurotoxic → paraesthesia and weakness
Abdominal pain
Mitotic inhibitor Etoposide Inhibits DNA synthesis by action on topoisomerase II Inhibits mitochondrial function Haematological malignancy Vomiting
Alopecia
Myelosuppression
Monoclonal antibody Rituximab Binds to CD20 protein → lyses B lymphocytes Lymphoma Hypotension
Chills and fever
Hypersensitivity reaction
Monoclonal antibody Trastuzumab (Herceptin) Binds to oncogenic protein human epidermal growth factor receptor 2 (HER2) Breast cancer that overexpress HER2
Protein kinase inhibitor Imatinib Inhibits oncogenic cytoplasmic kinase ( BCR/ABL ) & platelet-derived growth factor Chronic myeloid leukaemia Gastrointestinal upset
Headaches
Rashes (can get resistance)

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Mar 31, 2020 | Posted by in PHARMACY | Comments Off on Drugs and cancer

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