My opinion
 

By Dr. Chaitanya Varma
Corresponding Author Dr. Chaitanya Varma
Department of Pediatrics, KMC, Manipal, - India
Submitting Author Dr. Chaitanya Varma
MEDICAL EDUCATION

Molecular Targeted Therapy, Small Molecules, Monoclonal Antibodies,Antiangiogenesis

Varma C. Molecular Targeted Therapy: Cancer Therapy of the Future.. WebmedCentral MEDICAL EDUCATION 2012;3(6):WMC003496
doi: 10.9754/journal.wmc.2012.003496

This is an open-access article distributed under the terms of the Creative Commons Attribution License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
No
Submitted on: 17 Jun 2012 11:28:55 AM GMT
Published on: 18 Jun 2012 05:01:49 PM GMT

My opinion


Introduction:
Present day cancer treatment is multidisciplinary and usually includes various combinations of surgery, chemotherapy and radiation therapy. In spite of various advances, these treatments are still associated with toxicity risks. This has lead to the development of a fourth type of treatment called Targeted Therapy. During the late 20th century, it was realised that mutations in proto-oncogene and deletion of tumor suppressor genes can lead to carcinogenesis. Targeted therapy employs small chemical molecules or other substances, such as monoclonal antibodies, to  interfere with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with rapidly dividing cells like in traditional chemotherapy . Molecular Targeted Therapy (MTT) has an advantage of high therapeutic index, high selectivity and low toxicity.

Types of Targeted Therapy:
Small molecule drugs: Small molecule drugs have the ability to pass through cell membranes including plasma membrane1.  They can be used to interfere with specific areas of the target proteins located either outside or inside the cell, modify its enz activity or its interaction with other molecules and inhibit key signaling pathways that lead to carcinogenesis. These pathways include signal transduction via the activation of kinases, programmed cell death or “apoptosis”, regulation of gene transcription, or tumor angiogenesis. Imatinib was developed in the late 1990’s by biochemist Nicholas Lydon, oncologist Brian Drucker  and Charles Sawyer. Imatinib (Gleevec) received FDA approval in May 2001 and was hailed by TIME magazine as the "magic bullet” that can cure cancer .Originally developed as a specific inhibitor of the bcr/abl tyrosine kinase that characterizes chronic myeloid leukemia (CML), this drug was subsequently found to inhibit the activity of several other tyrosine kinases, and the platelet-derived growth factor (PDGF) receptor. Imatinib inhibits these kinases by binding to the active site on the kinase molecule. Some kinases are required for the continued survival of cancer cells, and inhibition of these kinases results in the death of the cancer cells. Nilotinib and Dasatinib are second generation drugs that are currently in the last stage of clinical trials. Small molecules can be used not only to inhibit the function of cellular enzymes, but also to activate them like the Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL). TRAIL binds to and activates two distinct cell surface receptors called Death Receptor 4 (DR4) and Death Receptor 5 (DR5) and lead to the activation of pathways within the cell that ultimately lead to programmed cell death (apoptosis).

Monoclonal Antibodies: Monoclonal antibodies (MAbs) are created from a single cell type and act by recognizing the protein on the surface of the cell and then locking onto it2. Monoclonal antibodies can interfere with the interaction of signaling molecules with receptors on the outside of a cell which often activates pathways inside the cancer cell.  Antibodies can be engineered to interact with very specific targets and so have a high degree of specificity which helps avoid unwanted side effects. Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukaemia (CLL).

Angiogenesis Inhibitors:  A theory proposed by surgeon Judah Folkman in 1971, that if the development of new blood vessels could be stopped, a tumor could not grow or spread, is the basis for research into antiangiogenic drugs. Interferon-alpha and Thalidomide are believed to have some ability to inhibit angiogenesis and are being studied in specific cancer types of cancers. Many antiangiogenesis agents are still under clinical trials and require FDA approval3 .

Therapeutic Cancer Vaccines: Cancer cells are not recognised by the body’s immune system and hence no immune response is mounted against them which leaves them to potentially develop into tumors. Some cancers suppress the body’s immune systems. Therapeutic cancer vaccines try to activate the body's immune system to make it recognize and attack cancer cells4. They are used on patients who are already undergoing treatment .The cancer vaccine may contain inactivated cancer cells, viruses that express tumor antigens, or any antigens that are overexpressed by cancer cells. An adjuvant, usually Interleukin-2 is used to induce a strong immune response.

Conclusion


Future of Targeted Theraphy: Presently targeted therapy is being used as an adjuvant therapy in the treatment of haematological malignancies, solid organ tumors, neuroendocrine tumors and breast cancer, along with the other classical chemo treatments. The continued research into this field might result in it being one of the mainstay treatment modality in future cancer treatment.

References


1. Peter Büchler.Organic synthesis toward small molecule probes and drug. Proc Natl Acad Sci U S A. 2011 April 26; 108(17): 6699–6702.
2. Cathy Eng.The Evolving Role of Monoclonal Antibodies In Colorectal Cancer. Oncologist. 2010 January; 15(1): 73–84.
3. Jie Ma, David J. Waxman. Combination of antiangiogenesis with chemotherapy for more effective cancer treatment. Mol Cancer Ther. 2008 December; 7(12): 3670–3684.
4. Azam Bolhassani, Shima Safaiyan, Sima Rafati.Improvement of different vaccine delivery system for cancer therapy. Mol Cancer. 2011; 10: (3).

Source(s) of Funding


None

Competing Interests


None

Disclaimer


This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party.
Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website.

Reviews
2 reviews posted so far

Author's Opinion on
Posted by Prof. Sunil Kumar Joshi on 13 Aug 2012 07:34:11 AM GMT

Comments
0 comments posted so far

Please use this functionality to flag objectionable, inappropriate, inaccurate, and offensive content to WebmedCentral Team and the authors.

 

Author Comments
0 comments posted so far

 

What is article Popularity?

Article popularity is calculated by considering the scores: age of the article
Popularity = (P - 1) / (T + 2)^1.5
Where
P : points is the sum of individual scores, which includes article Views, Downloads, Reviews, Comments and their weightage

Scores   Weightage
Views Points X 1
Download Points X 2
Comment Points X 5
Review Points X 10
Points= sum(Views Points + Download Points + Comment Points + Review Points)
T : time since submission in hours.
P is subtracted by 1 to negate submitter's vote.
Age factor is (time since submission in hours plus two) to the power of 1.5.factor.

How Article Quality Works?

For each article Authors/Readers, Reviewers and WMC Editors can review/rate the articles. These ratings are used to determine Feedback Scores.

In most cases, article receive ratings in the range of 0 to 10. We calculate average of all the ratings and consider it as article quality.

Quality=Average(Authors/Readers Ratings + Reviewers Ratings + WMC Editor Ratings)