Targeting cancer metastasis with antibody therapeutics

Abstract

Cancer metastasis, the spread of disease from a primary to a distal site through the circulatory or lymphatic systems, accounts for over 90% of all cancer related deaths. Despite significant progress in the field of cancer therapy in recent years, mortality rates remain dramatically higher for patients with metastatic disease versus those with local or regional disease. Although there is clearly an urgent need to develop drugs that inhibit cancer spread, the overwhelming majority of anticancer therapies that have been developed to date are designed to inhibit tumor growth but fail to address the key stages of the metastatic process: invasion, intravasation, circulation, extravasation, and colonization. There is growing interest in engineering targeted therapeutics, such as antibody drugs, that inhibit various steps in the metastatic cascade. We present an overview of antibody therapeutic approaches, both in the pipeline and in the clinic, that disrupt the essential mechanisms that underlie cancer metastasis. These therapies include classes of antibodies that indirectly target metastasis, including anti‐integrin, anticadherin, and immune checkpoint blocking antibodies, as well as monoclonal and bispecific antibodies that are specifically designed to interrupt disease dissemination. Although few antimetastatic antibodies have achieved clinical success to date, there are many promising candidates in various stages of development, and novel targets and approaches are constantly emerging. Collectively, these efforts will enrich our understanding of the molecular drivers of metastasis, and the new strategies that arise promise to have a profound impact on the future of cancer therapeutic development. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Ubiquitin D Promotes Progression of Oral Squamous Cell Carcinoma via NF-Kappa B Signaling

“…To further examine the role of UBD in OSCC cell lines, we tested cell migration and invasion, which are two critical steps in tumor metastasis ( Steinbichler et al, 2020 ; Yang et al, 2021 ). We performed wound healing assay with transfected HN6 and CAL27 cells.…”

“…To further examine the role of UBD in OSCC cell lines, we tested cell migration and invasion, which are two critical steps in tumor metastasis (Steinbichler et al, 2020;Yang et al, 2021). We performed wound healing assay with trans- The P values represent probabilities for FAT10 expression levels between variable subgroups determined by a χ 2 test.…”

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

“…Metastasis is the leading cause of cancer death globally. 38 It is a complicated pathological process that involves multiple steps, including epithelial to mesenchymal transition, in which cancer cells transit between epithelial and mesenchymal states that facilitating cell dissemination. 39 Our results demonstrated that FUT7 siRNA inhibited the migration, invasion, and EMT of bladder cancer cells, while FUT7 cDNA promoted these cell behaviors (Figures 2 and 3).…”

Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics

“… 142 This pipeline is fueled by novel tools of antibody discovery, e.g., moving from target-led strategies to phenotypic screening approaches, 26 , 143 including targets associated with the various stages of the metastatic process and the tumor microenvironment. 144 Thereby, the “high-hanging fruits” regarding target biology, target exposure and antibody modes of action are being pursued. The development of intracellularly produced antibodies, so-called intrabodies, which have recently been shown to work in vivo , 145 , 146 provides opportunities for developing a different kind of viro-antibody therapy.…”