◥Thirty-four years since its discovery, NF-kB remains a transcription factor with great potential for cancer therapy. However, NF-kB-targeted therapies have yet to find a way to be clinically translatable. Here, we focus exclusively on the role of NF-kB in nonsmall cell lung cancer (NSCLC) and discuss its contributing effect on cancer hallmarks such as inflammation, proliferation, survival, apoptosis, angiogenesis, epithelial-mesenchymal transition, metastasis, stemness, metabolism, and therapy resistance. In addition, we present our current knowledge of the clinical significance of NF-kB and its involvement in the treatment of patients with NSCLC with chemotherapy, targeted therapies, and immunotherapy.
Breast cancer (BC) is a common cancer in women worldwide. Despite advances in treatment, up to 30% of women eventually relapse and die of metastatic breast cancer. Liquid biopsy analysis of circulating cell-free DNA fragments in the patients' blood can monitor clonality and evolving mutations as a surrogate for tumour biopsy. Next generation sequencing platforms and digital droplet PCR can be used to profile circulating tumour DNA from liquid biopsies; however, they are expensive and time consuming for clinical use. Here, we report a novel strategy with proof-of-concept data that supports the usage of loop-mediated isothermal amplification (LAMP) to detect PIK3CA c.3140 A > G (H1047R), a prevalent BC missense mutation that is attributed to BC tumour growth. Allele-specific primers were designed and optimized to detect the p.H1047R variant following the USS-sbLAMP method. The assay was developed with synthetic DNA templates and validated with DNA from two breast cancer cell-lines and two patient tumour tissue samples through a qPCR instrument and finally piloted on an ISFET enabled microchip. This work sets a foundation for BC mutational profiling on a Lab-on-Chip device, to help the early detection of patient relapse and to monitor efficacy of systemic therapies for personalised cancer patient management.Breast cancer (BC) has a lifetime incidence risk of 12%, with an overall survival of more than 70% of reported cases when early detection is possible 1,2 . Although surgery is capable of removing the primary tumour, minimal residual disease (MRD)/micrometastases may persist resulting in eventual resistance to therapy and recurrence 3 . MRD can often persist even after adjuvant therapy and can grow and spread overtime, remaining undetectable through mammograms, MRI scans and current tumour marker blood tests, such as CA-15-3 and CA 27.29 antigen assays 4 . These current tumour marker blood tests work as a cost-effective method to measure disease progression but do not provide information about mutational changes and heterogeneity of the primary tumour or MRD. With the development of new, non-cross-resistant treatments for breast cancer, early detection of MRD/micrometastases and mutational profiling of circulating tumour DNA (ctDNA) provides an attractive, cost-effective alternative approach to the detection of early signs of relapse and treatment switching.Previous research has proven that circulating free DNA (cfDNA) contains DNA fragments from cancer cells (ctDNA) that are released in blood, showing somatic mutations that reflect the original cancer and evolved clonal subtypes 5 . In particular, recent efforts have established that hotspot mutations in PIK3CA, a gene mutated in 20-40% of metastatic BC, are also commonly observed in screen-detected stage-1 BCs 6 . The PI3K protein is involved in the AKT/mTOR pathway and, when deregulated, leads to tumour-cell growth 7 . Investigation has
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