Personalized tumor therapy using patient-derived cancer tissues

Introduction: The number of cancer patients is increasing in Iran and worldwide. This challenge can only be met with the development of more effective and convenient therapies for cancer patients. Despite advances in the treatment of cancer patients, side effects occur and mortality remains high due to inappropriate therapy or resistance. Heterogeneity is commonplace in all cancer types and at several levels (intrinsic (genetic), epigenetic, positional, and at the population level). The cells of different tumor subpopulations communicate with each other and influence the behavior of other tumor cells. This implicates, each tumor behavior is complex and different and tailored therapies should be administered. Because cancer can now be sub-classified by its genetics (e.g., melanoma BRAF positive, breast cancer HER2 positive), in some clinics patients with melanoma, or breast cancer are now routinely offered tailored treatments. A targeted cancer therapy can greatly improve the chances of survival. For instance, about 30 percent of breast cancer cases are characterized by overexpression of the human epidermal growth factor receptor 2 (HER2). Antibody treatment (Trastuzumab) can reduce the recurrence of a tumor by 52 percent when used in combination with chemotherapy, in comparison to chemotherapy alone. Thus, identified HER2 overexpressing women will benefit from receiving drugs that target HER2 (Romond et al. 2005). Promising in the clinical setting, is the targeting of the BRAF kinase in melanoma using BRAF kinase inhibitors (e.g. Vemurafenib) (Holderfield et al. 2014). Patient-derived tumor tissues generated from fresh tumor specimens recapitulate the diversity of cancer and reflect histopathology, tumor behavior, and the metastatic properties of the original tumor and in vitro testing of individual tumor responses to anti-cancer drugs might improve personalization of cancer treatment. Effective selection can prevent unnecessary treatment that would mainly result in the unwanted side effects of the therapy.Objective: Our goal is to establish the first platform for personalized tumor therapy in Iran using patient-derived breast, melanoma and intestinal cancer tissues. They will be analyzed regarding drug screening, biomarker analysis and identification of sensitivity and resistance mechanisms. Methods: After patient recruitment in cooperation with clinics, tumor tissue units from breast, skin, intestine, obtained after surgery, are cultured. Characteristic properties with regard to response to therapeutics and resistances will be examined. In addition, tumor stem cells, extracellular matrix and vascularization will be investigated.

Keywords:

Personalize , therapy , cancer , tissue , drug , screening