The research and treatment of non-small cell lung cancer (NSCLC) have achieved some important advances in recent years. Nonetheless, the overall survival rates for NSCLC remain low, indicating the importance to effectively develop new therapies and improve current approaches. The understanding of the function of different biomarkers involved in NSCLC progression, survival and response to therapy are important for the development of early detection tools and treatment options. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (K-RAS) are two of the main significant biomarkers for the management of NSCLC. Mutations in these genes were associated with development and response to therapies. For example, the use of small molecule tyrosine kinase (TK) inhibitors and immunotherapy has led to benefits in some, but not all patients with altered EGFR. In contrast, there is still no effective approved drug to act upon patients harbouring K-RAS mutations. In addition, K-RAS mutations have been associated with lack of activity of TK inhibitors. However, promising approaches aimed to inhibit mutant K-RAS are currently under study. Therefore, this review will discuss these approaches and also EGFR therapies, and hopefully, it will draw attention to the need of continued research in the field in order to improve the outcomes in NSCLC patients.

Colorectal cancer is the second most common cause of cancer-related mortality in adults. Understanding colorectal tumorigenesis at both the cellular and molecular levels is crucial for developing effective treatment options. Forty-one biopsy samples from patients with metastatic CRC (mCRC) were collected at Split University Hospital in Croatia. A total of 41 patients (21 with microsatellite unstable tumours and 20 with microsatellite stable tumours) were randomly included in the study. Immunolabelling of cGAS and STING in metastatic CRC was performed and further complemented by histological classification, tumour grade, and KRAS, NRAS, and BRAF mutational status of mCRC. In bivariate analysis, elevated expression of cGAS and STING was positively associated with MSI-H colon cancer (Fisher’s exact test, both p = 0.0203). Combined expression analysis of cGAS and STING showed a significantly higher percentage of patients with mCRC MSI-H with a fully or partially activated cGAS-STING signalling pathway (chi-square test, p = 0.0050). After adjusting for age, sex, and STING expression, increased cGAS expression remained significantly associated with MSI-H colon cancer in a multiple logistic regression model (β = 1.588, SE = ±0.799, p = 0.047). The cGAS-STING signalling axis represents a compelling new target for optimization of immune checkpoint inhibitor therapeutic approaches in patients with MSI-H stage IV CRC.

The complex structure of glycosphingolipids (GSLs) supports their important role in cell function as modulators of growth factor receptors and glutamine transporters in plasma membranes. The aberrant composition of clustered GSLs within signaling platforms, so-called lipid rafts, inevitably leads to tumorigenesis due to disturbed growth factor signal transduction and excessive uptake of glutamine and other molecules needed for increased energy and structural molecule cell supply. GSLs are also involved in plasma membrane processes such as cell adhesion, and their transition converts cells from epithelial to mesenchymal with features required for cell migration and metastasis. Glutamine activates the mechanistic target of rapamycin complex 1 (mTORC1), resulting in nucleotide synthesis and proliferation. In addition, glutamine contributes to the cancer stem cell GD2 ganglioside-positive phenotype in the triple-negative breast cancer cell line MDA-MB-231. Thieno[2,3-b]pyridine derivative possesses higher cytotoxicity against MDA-MB-231 than against MCF-7 cells and induces a shift to aerobic metabolism and a decrease in S(6)nLc4Cer GSL-positive cancer stem cells in the MDA-MB-231 cell line. In this review, we discuss findings in MDA-MB-231, MCF-7, and other breast cancer cell lines concerning their differences in growth factor receptors and recent knowledge of the main biochemical pathways delivering distinct glycosphingolipid patterns during tumorigenesis and therapy.