Anti-cancer Drugs
Drug Targets
differences between
normal and tumour cells
Proliferation
Differentiation
Invasiveness
Metastasis
Host biochemical
pathways
Angiogenesis
Immune system
Inflammation
Problems with
anti-cancer
chemotheraphy
because scells are derived from self, most therapies rely on quantitative (proliferation/growth) rather than qualitative differences.
host cells are invariably effected
most drugs
Chemotheraphy is most often used with other
modalities of therapy, such as Surgery and Radiation
adhesion molecules & Metalloproteases Inhibitors
Retinoids
Adhesion molecules & Metalloproteases Inhibitors
Anti-cancer drugs have low therapeutic index
sever side effects
Bone Marrow
Healing impairment
Alopecia
Damage to gastrointestinal epithelium
Depression of growth
Sterility
Teratogenicity
Severe nausea
heterogeneity of tumour cells, makes targeting very difficult, as each cell type will respond differently to each drug
Cancer cell susceptibility to a given drug also
depends on the stage of the cell cycle
A fraction of cancer cells are actively dividing and they are the drug targets, where some population is in a dormant state but can reenter the proliferating cells
minimal immune response to cancer cells
drug resistance
Extravasation, Tumor Lysis Syndrome
Pharmacogenetics
Chemotherapeutic drugs
Alkylating agents
Anti-metabolites
Cytotoxic Antibiotics
Plant derivatives
Hormone based therapy
Protein Kinases Inhibitors
Monoclonal Antibodies
Antineoplastic drugs
originated from mustard gas, which was
observed to inhibit white blood cell proliferation
crosslink DNA bases (especially Guanine),
inhibiting DNA replication
as a side effect mutations due to
this treatment can cause cancer
modified natural metabolites, which are supposed to be incorporated to cancer cells and inhibit their proliferation
Methotrexate
substitutes for folic acid,
inhibiting nucleotide production
can treat Malaria and Cancer
5'Fluorouracil
Bleomycin
Dactinomycin
Topoisomerase II inhibitor
prevents sealing the nick
microtubules inhibitors
microtubules are important for cell proliferation ad migration
prevent the addition of microtubule dimers to the microtubule tubes
Imantinib
Tyrosine Kinase inhibitor
tyrosine kinases are important for proliferation
Goldie-Coldman hypothesis
the probability of resistance clones = mutation rate x number of tumour cells
cancer cells are detectable at 10^9 cell count and lethal at 10^12
after the cancer cell count exceeds 10^8 it is not possible to treat the tumour with a single modality of treatment, cause it immediately develops resistance.
Combined theraphy - often 3 or more different treatments are applied together to reduce the probability of developing the resistance to treatment
Curative therapy for
testicular cancer
Bleomycin
Etoposide
Cisplatin
drugs must be active against the
tumour through different mechanisms,
drugs must have limited overlapping toxicity