Lung cancer is a serious health problem and leading cause of death worldwide due to its high incidence and mortality. More than 80% of lung cancers feature a non-small cell histology. Over few decades, systemic chemotherapy and surgery are the only treatment options in this type of tumor but due to their limited efficacy and overall poor survival of patients, there is an urge to develop newer therapeutic strategies which circumvent the problems. Enhanced knowledge of translational science and molecular biology have revealed that lung tumors carry diverse driver gene mutations and adopt different intracellular pathways leading to carcinogenesis. Hence, the development of targeted agents against molecular subgroups harboring critical mutations is an attractive approach for therapeutic treatment. Targeted therapies are clearly more preferred nowadays over systemic therapies because they target tumor specific molecules resulting with enhanced activity and reduced toxicity to normal tissues. Thus, this review encompasses comprehensive updates on targeted therapies for the driver mutations in non-small cell lung cancer (NSCLC) and the potential challenges of acquired drug resistance faced in the field of targeted therapy along with the imminent newer treatment modalities against lung cancer.

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Microsatellite Instability (MSI) is a hallmark of colorectal cancer (CRC) and occurs in 15–16% of CRC. Molecular biological information of CRC in South Africa (SA) is largely unrecorded. This study was undertaken to determine the frequency of MSI, with particular reference to Lynch syndrome (LS) with a view to improve surveillance and prevention strategies. This was a retrospective study on CRC samples diagnosed between 2011–2015 at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Samples diagnosed between 2011–2012 were screened for MSI by PCR and mismatch repair (MMR) immunohistochemistry (IHC), and additional BRAFV600E mutational analysis performed. T-tests, Fischer’s exact and Chi square statistical tests were applied. Twelve percent of patients displayed MSI, with increased frequency in black (15%) versus other ethnic group (OEG) (8%) patients. MSI patients were significantly younger than microsatellite stable (MSS) patients, however when stratified by ethnicity, black patients were predominantly younger (median age: 47), with increased MSH2/6 loss, and no BRAF mutations. These findings suggest a large proportion of young black SA CRC patients develop via the LS pathway due to earlier age onset and predominant MSH2/6 protein loss. SA patients of other ethnicities appear to follow the more well established sporadic MSI pathway.

Lung cancer stem cells are supposed to be the main drivers of tumor initiation, maintenance, drug resistance, and relapse of the disease. Hence, identification of the cellular and molecular aspects of these cells is a prerequisite for targeted therapy of lung cancer. Currently, analysis of circulating tumor cells has the potential to become the main diagnostic technique to monitor disease progression or therapeutic response as it is non-invasive. However, accurate detection of circulating tumor cells has remained a challenge, as epithelial cell markers used so far are not always trustworthy for detecting circulating tumor cells, especially during epithelial-mesenchymal transition. As cancer stem cells are the only culprit to initiate metastatic tumors, our aim was to isolate and characterize circulating tumor stem cells rather than circulating tumor cells from the peripheral blood of NSCLC adenocarcinoma as limited data are available addressing the gene expression profiling of lung cancer stem cells. Here, we reveal that CD44(+)/CD24(−) population in circulation not only exhibit stem cell-related genes but also possess epithelial-mesenchymal transition characteristics. In conclusion, the use of one or more cancer stem cell markers along with epithelial, mesenchymal and epithelial mesenchymal transition markers will prospectively provide the most precise assessment of the threat for recurrence and metastatic disease and has a great potential for forthcoming applications in harvesting circulating tumor stem cells and their downstream applications. Our results will aid in developing diagnostic and prognostic modalities and personalized treatment regimens like dendritic cell-based immunotherapy that can be utilized for targeting and eliminating circulating tumor stem cells, to significantly reduce the possibility of relapse and improve clinical outcomes.

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