Dept. of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Department of Wood Processing Technology, Mendel University in Brno, Brno, Czech Republic.
Med Hypotheses. 2018 Dec;121:10-14. doi: 10.1016/j.mehy.2018.09.003. Epub 2018 Sep 6.
Colon cancer is one of the fatal forms of cancer all round the world with a equal frequency of occurrence in both male and female population. Mutational changes and defects in APC (Adenomatous Polyposis Coli) and DNA mismatch repair genes accompanied by genetic chaos in oncogenic pathways leads to colon cancer. Intensive study on pathogenesis of colon cancer has been made to decipher the mechanisms underlying the development and progress of the disease so as to develop effective treatment. However, a complete therapeutic regimen is still not available for combating this deadly disease. Hurdles faced by chemotherapy include drug resistance due to P-glycoprotein transporters, untoward effects on normal cells, high cost, bio-burden of the therapy, and the most dreadful drawback is cancer relapse. The concept of cancer relapse is related to development of oxidative stress that causes cell apoptosis. If the level of oxidative stress is inadequate to cause apoptosis then it leads to cell dormancy which may revive post chemotherapy. This hypothesis aims to put forward a combinatorial approach that includes utilizing a cost effective, biocompatible and environmentally benign nanoparticulate carrier made up of lignin, loaded with anti-cancer agent and P-gp modulator, and functionalized with ligand for CD44 receptors that are over expressed on cancer cells. Antioxidant effect of lignin will overcome dormancy of cancer cells making it possible for cell cycle specific drugs to kill them and prevent relapse and active targeting will prevent untoward effects on normal cells. Thus a robust and wholesome formulation can be developed to combat colon cancer.
结肠癌是全球范围内致命的癌症之一，男性和女性的发病率相当。APC（结肠腺瘤性息肉病）和 DNA 错配修复基因的突变和缺陷，以及致癌途径中的遗传混乱，导致了结肠癌的发生。目前已经对结肠癌的发病机制进行了深入研究，以揭示疾病发展和进展的机制，从而开发有效的治疗方法。然而，针对这种致命疾病仍然没有完整的治疗方案。化疗面临的障碍包括 P-糖蛋白转运体的耐药性、对正常细胞的不良影响、高成本、治疗的生物负担，以及最可怕的缺点是癌症复发。癌症复发的概念与氧化应激的发展有关，氧化应激会导致细胞凋亡。如果氧化应激水平不足以引起凋亡，那么它会导致细胞休眠，这可能会在化疗后重新出现。本研究旨在提出一种联合治疗方法，包括利用成本效益高、生物相容性好、环境友好的木质素纳米颗粒载体，负载抗癌药物和 P-糖蛋白调节剂，并通过配体对 CD44 受体进行功能化，CD44 受体在癌细胞上过度表达。木质素的抗氧化作用可以克服癌细胞的休眠，使细胞周期特异性药物能够杀死它们，从而防止复发，主动靶向可以防止对正常细胞的不良影响。因此，可以开发出一种强大的、全面的制剂来对抗结肠癌。
