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HEA567 Pharmacology For Health Professionals
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HEA567 Pharmacology For Health Professionals
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Course Code: HEA567
University: Charles Darwin University
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Country: Australia
Question
Reflective Journal 1- Monoclonal Antibody Drugs
Reflect on your understanding with regard to Immunology and the current rapid development and introduction of monoclonal antibody drugs into clinical practice (they are mainly used as anti-inflammatory agents or cancer chemotherapeutic agents). Use one example to elaborate your reflection and how this may lead to personalised medical treatment in future.
Answer
Reflective Journal One: Monoclonal Antibody Drugs
Monoclonal Antibody Drugs
Targeting of tumor- causing macrophages is becoming increasingly important in cancer treatment. Monoclonal antibodies (mAbs) have proved to be essential in cancer treatment due to their superior affinity for target antigens, specificity1 and blocking mechanism. Cancer patients of all kinds can benefit immensely from this tool. In this journal, we focus on how mAbs is used in the treatment of breast cancer with a touch of its possible utilization in personalized medical care in future.
Panowski et al. opine that targeted therapies work by means of a blocking mechanism that impedes the operations of essential biochemical pathways. In addition, they also block mutant proteins that are vital for tumor cell proliferation and survival2. In doing so, mAbs slow down tumor progression and stimulate considerable retrogressions in molecularly expressed subsets of cancer patients. BCR-ABL kinase inhibitor imatinib was the initial molecule known to have stimulated comprehensive cytogenetic responses in nearly 80% of chronic myelogenous leukemia patients3. The kinase inhibition capability has found use in treatment of many types of cancers. Future personalized medical care ought to take the abilities of mAbs with regards to BCR-ABL kinase imatinib inhibition into consideration in making giving the tool priority in patients whose metastatic cancer is at the initial stages.
Emerging Drug-resistant Variants
Further investigations into the genetic pathways driving tumor growth and nourishment have revealed additional oncoproteins that are essential for their sustenance. They include epidermal growth factor receptor (EGFR), BRAF, KIT, as well as anaplastic lymphoma kinase (ALK) 4. Imatinib has an analogous effect. Tiny molecule inhibitors of the kinases have been known to continuous notable tumor regressions in selected patients. Nevertheless, recessions are habitually trailed by a gradual development of the disease secondary to emerging drug-resistant variants5. Resistance has been associated with resultant mutations occurring in the affected protein as well as compensatory alterations occurring in the affected pathway consequently circumventing the drug-interceded inhibition6 &7. Consequently, targeted rehabilitation may prompt remarkable tumor regressions that are usually transient thereby constraining the general clinical advantage8. This is crucial information for clinicians to make determinations in using targeted therapies as a transitory cancer medication. By so doing, future cancer treatment would have personalized medical for each patient in a manner that meets the needs of the present with little compromise, if any.
Molecular procedures with capabilities to modify antibody pharmacokinetics, effector function, range, and immune-capabilities keep presenting themselves as crucial features in the development of innovative antibody-centered treatments. There exist substantiated claims based on clinical experiments of antibodies among cancer patients with regards to the significance of iterative tactics in the assortment of antigen marks and optimum antibodies. This constitutes the avidity and affinity (which are traits of antibodies). The selection of antibody structure and therapeutic tactic (inclusive of indication of retraction or immune effector function) as well as the prerequisite to thoroughly scrutinize the pharmacokinetic and pharmacodynamic characteristics of antibodies are important considerations in future clinical trials in their early stages.
Personalized medical treatment needs to take into account the nature of the target antigen in the computation of safety and efficacy of therapeutic mAbs. It is preferable that that copious amount of the antigen exists singularly on the exterior of cancer cells9. The release of antigen ought to be marginal considering their capability to bind the antibody circulating with a possible consequent effect of inhibiting ample antibody binding the tumour10. In case the preferred mechanism of action is either ADCC or CDC, then it is appropriate that the antigen–mAb composite is not promptly internalized in order to amplify the accessibility of the Fc locale of the immune effector cells in addition to complement proteins11. Contrastingly, suitable internalization is enviable in the events that antibodies or proteins used to delivering toxins into the cancer cell are available12. How does affect the personalization of medical? Well, different metastatic cancer cells react to mAbs treatment with dissimilar efficacies. As such, targeting will need to be done in clusters of patients with metastatic cancer cell whose mAbs treatment elicits the highest efficacy and safety alike.
Conclusion
Significant efforts have been put towards pinpointing new antigen targets appropriate for antibody-derived treatments in cancer. The fruitful development of suitable antibodies does entail an intricate procedure of scientific and preclinical observations, abreast by profound comprehension of cancer biology as well as the characteristics of antibodies13&14. All these are done at the backdrop of a keen interest in observing the efficacy and safety with regards to the stage of use15. This is made possible by the fact that mAbs have the capabilities to modify antibody pharmacokinetics, effector function, range and immune-capabilities keep presenting themselves as crucial features in the development of innovative antibody-centered treatments.
Reference List
Panowski S, Bhakta S, Raab H, Polakis P, Junutula JR. Site-specific antibody-drug conjugates for cancer therapy. mAbs 2014 Jan 1 (Vol. 6, No. 1, pp. 34-45). Taylor & Francis.
Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nature reviews cancer. 2012 Apr;12(4):237.
Hughes TP, Hochhaus A, Branford S, Müller MC, Kaeda JS, Foroni L, Druker BJ, Guilhot F, Larson RA, O’Brien SG, Rudoltz MS. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the international randomized study of interferon versus STI571 (IRIS). Blood. 2010 Jan 1:blood-2010.
Haber DA, Gray NS, Baselga J. The evolving war on cancer.Cell.2011;145:19–24.
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. New England Journal of Medicine. 2001 Mar 15;344(11):783-92.
Adams GP, Weiner LM. Monoclonal antibody therapy of cancer. Nature biotechnology. 2005 Sep;23(9):1147.
Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nature Reviews Cancer. 2012 Apr;12(4):278.
Brannon-Peppas L, Blanchette JO. Nanoparticle and targeted systems for cancer therapy. Advanced drug delivery reviews. 2012 Dec 1;64:206-12.
Weiner LM, Surana R, Wang S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nature Reviews Immunology. 2010 May;10(5):317.
Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, Bencardino K. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012 Jun;486(7404):532.
Guo Y, Xu F, Lu T, Duan Z, Zhang Z. Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer treatment reviews. 2012 Nov 1;38(7):904-10.
Rowland A, Dias MM, Wiese MD, Kichenadasse G, McKinnon RA, Karapetis CS, Sorich MJ. Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer. British journal of cancer. 2015 Jun;112(12):1888.
Burris III HA, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, Tan-Chiu E, Krop IE, Michaelson RA, Girish S, Amler L. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)–positive breast cancer after prior HER2-directed therapy. Journal of Clinical Oncology. 2010 Dec 20;29(4):398-405.
Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, Rey-Giraud F, Pradel LP, Feuerhake F, Klaman I, Jones T. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer cell. 2014 Jun 16;25(6):846-59.
Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market. InMAbs 2015 Jan 2 (Vol. 7, No. 1, pp. 9-14). Taylor & Francis.
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