Drug resistance and personalized medicine

سال انتشار: 1396
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 542

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شناسه ملی سند علمی:

IPMCMED02_133

تاریخ نمایه سازی: 29 فروردین 1397

چکیده مقاله:

Drug resistance is one the causes of limited efficacy of cancer therapy and could be intrinsic or acquired. In fact, heterogeneity in gene dosage and signaling pathways in cancer cell populations renders them intrinsically more resistant to therapeutic approaches. For instance, colorectal cancer patients harboring mutation in KRAS do not respond to EGFR inhibitors such as Cetuximab and panitumumab. Resistance to drugs could be acquired through various mechanisms: 1- secondary genetic variations in drug targets; an example is BCR-ABL amplification seen in imabtinib-resistant CML patients. 2- pathway independent resistance. A typical example is the impact of tumor microenvironment on the efficacy of inhibitors of polo-like kinase and Janus-activated kinase-2. 3- drug resistance acquired through activation of alternative mechanisms. 4- resistance due to the existence of cancer stem cells (CSC).Hence, identifying drug resistance-related mechanisms in the case of every patient prior to commencing the treatment is of major importance. Making use of NGS, proteomics and metabolomics data would be of great help in this regard. To investigate drug resistance, different approaches can be adopted, among which are: 1- examination of the sensitivity of patient biopsy-derived cells to drug. In this case, patients’ biopsies are treated with different drugs and generally, the level of cell death is measured. 2- patient-derived xenograft tumor model, in which, patient biopsy is implanted orthotopically into an animal model and the in vivo impacts are assessed. 3- In situ assessments, which are based upon intratumoral injection of microdasage of drugs with the help of newly designed devices. In fact, personalized medicine provides the opportunity for applying the appropriate drugs with the perfect timing and at a suitable dosage with minimal or even no toxicity.

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نویسندگان

Roya Sajed

Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

Roya Ghods

Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.