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Targeted therapy

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Targeted therapy

Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth,[1] rather than by simply interfering with all rapidly dividing cells (e.g. with traditional chemotherapy). Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy (and thus distinguished from chemotherapy, that is, cytotoxic therapy). However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.

Targeted cancer therapies are expected to be more effective than older forms of treatments and less harmful to normal cells. Many targeted therapies are examples of immunotherapy (using immune mechanisms for therapeutic goals) developed by the field of cancer immunology. Thus, as immunomodulators, they are one type of biological response modifiers.

There are targeted therapies for breast cancer, multiple myeloma, lymphoma, prostate cancer, melanoma and other cancers.[2]

The definitive experiments that showed that targeted therapy would reverse the malignant phenotype of tumor cells involved treating Her2/neu transformed cells with monoclonal antibodies in vitro and in vivo by Mark Greene’s laboratory and reported from 1985.[3]

Some have challenged the use of the term, stating that drugs usually associated with the term are insufficiently selective.[4] The phrase occasionally appears in scare quotes: "targeted therapy".[5] Targeted therapies may also be described as "chemotherapy" or "non-cytotoxic chemotherapy", as "chemotherapy" strictly means only "treatment by chemicals". But in typical medical and general usage "chemotherapy" is now mostly used specifically for "traditional" cytotoxic chemotherapy.

Types

The main categories of targeted therapy are currently small molecules and monoclonal antibodies.

Tyrosine kinase inhibitors (small molecules)

Mechanism of imatinib

Many are tyrosine-kinase inhibitors.

Small molecule drug conjugates

  • Vintafolide is a small molecule drug conjugate consisting of a small molecule targeting the folate receptor. It is currently in clinical trials for platinum-resistant ovarian cancer (PROCEED trial) and a Phase 2b study(TARGET trial) in non-small-cell lung carcinoma (NSCLC).[13]

Serine/threonine kinase inhibitors (small molecules)

Monoclonal antibodies

Several are in development and a few have been licensed by the FDA. Examples of licensed monoclonal antibodies include:

Many Antibody-drug conjugates (ADCs) are being developed. See also ADEPT (Antibody-directed enzyme prodrug therapy).

Progress and future

In the U.S., the National Cancer Institute's Molecular Targets Development Program (MTDP) aims to identify and evaluate molecular targets that may be candidates for drug development.

See also

References

  1. ^
  2. ^ NCI: Targeted Therapy tutorials
  3. ^

  4. ^
  5. ^
  6. ^
  7. ^
  8. ^
  9. ^
  10. ^
  11. ^ http://clinicaltrials.gov/ct2/results?term=apatinib
  12. ^
  13. ^ [1]
  14. ^

External links

  • CancerDriver : a free and open database to find targeted therapies according to the patient's features.
  • Targeted Therapy Database (TTD) [2] from the Melanoma Molecular Map Project [3]
  • Targeted therapy Fact sheet from the U.S. National Cancer Institute
  • Molecular Oncology: Receptor-Based Therapy Special issue of Journal of Clinical Oncology (April 10, 2005) dedicated to targeted therapies in cancer treatment
  • Targeting Targeted Therapy New England Journal of Medicine (2004)
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