Leucine-rich alpha-2-glycoprotein-1 (LRG1) has received much attention as a prognostic indicator in cancer therapy where high serum levels generally predict a poor outcome. Recently, it has been shown to play an active role in cancer progression and is being pursued as a novel target in cancer therapy. LRG1 acts in neovascularization of tumors resulting in weakened blood vessels and ineffective delivery of chemotherapeutic drugs. A monoclonal antibody (mAb) against LRG1 has shown efficacy in blocking this function of LRG1, normalizing the vasculature, and improving drug delivery in mice. Extracellular LRG1 is also anti-apoptotic and promotes cell proliferation and metastasis, all through epidermal growth factor receptor family signaling. In mice, anti-LRG1 antibody therapy has been shown to inhibit these effects of extracellular LRG1 and to enhance the anti-cancer effect of immune checkpoint blockade (ICB) therapy in mice. Pre-clinical testing of the humanized version of the LRG1 mAb is underway in the United Kingdom. Intracellular LRG1 has been reported to inhibit apoptosis by blocking the binding of Cyt c to apoptotic protease activating factor1 (Apaf-1) and to have other cytoplasmic functions. A nanoscale proteolysis targeting chimera (nano-PROTAC) with improved cytoplasmic delivery has been developed which enhanced apoptosis in tumors of mice. Targeting LRG1 in the aberrant angiogenesis of endothelial cells and the LRG1-Cyt c-Apaf-1 axis in cancer cells, along with other putative intracellular interactions of LRG1, show potential as supplementary, if not alternative, approaches to cancer therapy.
We report a deceptive presentation of Squamous Cell Carcinoma of the Cervix in a 54-year-old postmenopausal woman who presented with postmenopausal bleeding associated with lower abdominal pain for a 3-month duration, with a normal-looking ectocervix. She was diagnosed with squamous cell carcinoma on a pap smear and cervical biopsy. Magnetic resonance imaging revealed an irregular endometrial cavity contour, and a T2 hyperintense lesion was seen (2.3 × 0.8 cm) involving the posterior lip of the cervix at the junction of stroma and endocervix with a mural spread along the uterine myometrium. Histopathology after Wertheim's hysterectomy revealed a squamous cell carcinoma of the endocervix, Stage pT1b3, that had spread superficially to the endometrium, myometrium, and left salpinx. The detection of immunohistochemical expression of p16, p63, and negative for ER and PR in the lesions of the cervix and the endometrium suggests that these two lesions are etiologically related, favoring the possibility of endometrial SCC secondary to cervical SCC.
