Cytocapsular tube network-tumor system is an integrated physical target for the highly effective and efficient pharmacotherapy of solid cancers

Abstract

AbstractCancer is a leading cause of human lethality and cancer drug pan-resistant tumor metastasis (cdp-rtm) is a major source of cancer death. The integrated cytocapsular tube (CCT) networktumor system (CNTS) is essential for cancer evolution procedures including cancer cell proliferation, migration and dissemination in CCT networks, new tumor growth in CCT terminals, conventional cancer drug pan-resistance, and tumor relapse. The preclinical screening experimentations with CCTs and networks are necessary prerequisites for the discovery and development of cancer drug candidates for efficient clinical trials, and effective and precise clinical cancer pharmacotherapy. However, it is unknown whether the popularly employed conventional mouse experimentations for preclinical therapeutic development generate CCTs and networks. Here, we comprehensively investigated the cancer cell line derived xenografts (CDX) of 8 kinds of cancer cell lines, and patient cancer cells derived-xenografts (PDX) with 16 kinds of clinical primary and metastatic malignant tumor cells in multiple cancer stages by immunohistochemistry staining assays with CCT marker protein antibodies of anti-CM-01 antibodies. We found that there are no CCTs or CCT networks in all these examined 16 CDX and 22 PDX transplanted tumors. Our data evidenced that the conventional transplantation tumors for preclinical therapeutic development do not engender CCTs or CNTS, which is consistent with and provides an explanation of the poor clinical outcomes of the marketed cancer drugs. This study demonstrated that CCT network-tumor system (CNTS) is an integrated physical target for pharmacotherapy, and that preclinical experimentations engendering CNTS (such as CCT xenograft, CCTX) should be employed for the discovery and development of highly effective and efficient cancer drugs aimed for cure of solid cancers.