Notes: Cancer – Causes and Drugs

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A woman after chemotherapy

Cancer is pretty much caused by your cells growing too much.  Either they stop responding to the signal which tell them to stop growing, or they start generating too many which tell them to grow.

Either way, cancerous cells start growing and threaten to continue doing so until the body is dead.

As such, treatments tend to focus on stopping their growth.

Cellular Mechanisms of Oncogenesis:

Mutations relating to p53

50% of solid tumors have a mutation in p53, a protein that plays many roles in protecting the cell from cancer.  p53 stops the cell in G1 if there is DNA damage, preventing replication.  Acting as a transcription factor, it activates genes responsible for arresting the cell cycle.  It also promotes repair of damaged DNA and, failing that, causes apoptosis.

Mutation in Von Hippel Landau

Von Hippel Lindau is an e3 ring structure ubiquinase.  It plays a role in ubiquitinating Hypoxia Inducible Factor, marking it for degredation.  Without this function, HIF goes on to promote cellular factors that promote angiogenesis such as vascular endothelial growth factor, VEGF.

Ras mutations

Ras is an GTPase which regulates cellular signaling.  A mutation in it can prevent its inhibitory role, which can lead to the formation of a tumor.

Drug treatments of Cancer

Vinca Alkaloids

The vinca alkaloids bind near the GTP binding pocket on microtubules.  This prevents them from growing.  Because microtubules need to grow to be functional, this effectively stops them, and keeps the cell in the mitotic phase.

Vinblastine: used for lymphoma, Kaposi’s sarcoma, and testicular cancer.  Side effects include myelosuppresion and hypertension.  Bone marrow suppression is dose limiting.

Vincristine: used for leukemias, Hodgkin’s disease, and rhabomyosarcoma.  Side effects include peripheral neuropathy and myopathy.  The neuoropathy is the dose limiting issue.

The taxanes also interfere with microtubules.  Unlike the Vinca Alkaloids, they promote stability.  Because they make the microtubules rigid and extended, this causes them to break down eventually, which also keeps the cell in the mitotic phase.

Taxol or Paclitaxel: used for many solid tumors, especially breast, ovarian, and lung cancer.  Side effects include myelosuppresion, hypersensitivity, and peripheral neuropathy, which is the dose-limiting effect.

The bleomycins bind to DNA and chelate iron.  This activity promotes the creation of free radicals which damage the DNA.  Stops incorporation of thymidine into DNA.  The biggest side effect and concern around the bleomycins is the potential for pulmonary fibrosis.

Cisplatin cross-links DNA strands which causes damage.  Used in testicular cancer especially, as well as general genito-urinary cancers.  Nephrotoxicity is the biggest concern with this medication.

6-Mercaptopurine: this is an inosine analogue that prevents the interconversion between purine nucleotides.  Basically, it lowers cellular levels of AMP and GMP which are needed for nucleotide synthesis.  Mainly used for acute lymphoblastic leukemia.

Methotrexate: inhibits DHFR which is needed to generate folic acid forms for nucleotide synthesis.  Folinic acid can be coadministered to lower toxicity/enhance effectiveness.

Bevacizumab: this is a humanized monoclonal antibody against VEGF, a messenger that promotes angiogenesis.  Modest benefit, but quite expensive.

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Pharmaceutical analyst who loves blogging about health and medical issues. Has written more than 150 articles and a book on attention deficit disorder. Correctly predicted delayed approval of Bydureon, approval of Provenge by FDA, and the non-approval of Acthar on June 11.

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1 COMMENT

  1. Having overcome hodgkins, this was good to read. Thank you for this.

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