Recent Advances in Development of New Technology in Pre and Intra Operative Breast Cancer Diagnoses

Breast cancer is the second most occurring malignant disease in women. 1 in 9 women will be affected by this disease in their lifetime. The gold standard for breast cancer screening is the mammographic technique, which has its limitations especially for women aged below 40 as a result of breast density. Ongoing research are exploring techniques that can improve detection accuracy as well as reduce time and money spent in advanced stage treatment options. This review paper highlights the different technologies that have been developed for breast cancer diagnoses.

Mini-Review: PDPK1 (3-phosphoinositide dependent protein kinase-1), An Emerging Cancer Stem Cell Target

Cancer stem cells (CSCs) are subpopulations of tumor cells that possess abilities for self-renewal, differentiation, and tumor initiation. These rare but therapy-recalcitrant cells are assumed to repopulate tumors following administration of systemic chemotherapy driving therapy failure, tumor recurrence, and disease progression. In early clinical trials, anti-CSC therapies have found limited success to-date possibly due to the inherent heterogeneity and plasticity of CSCs and the incomplete characterization of essential CSC targets. Here, we review the role of 3-phosphoinositide dependent protein kinase-1 (PDPK1) as an emerging CSC target. While most previous studies have relied on CSC models which are based on lineage and tissue-specific marker profiles to define the relationships between putative target and CSC traits, this review discusses PDPK1 and its role in CSC biology with an emphasis on CSC systems which are based on proposed function like label-retaining cancer cells (LRCCs).

Outcome measures following Sono and Photodynamic Therapy – A Case Series

Sono and Photodynamic Therapy (SPDT) is a novel therapeutic modality that utilises a non-toxic photosensitive agent with reported ultrasound-activated properties. SPDT has previously demonstrated significant tumour cell inhibition in animal studies. There has been much research into the efficacy of photodynamic therapy and development in understanding of the underlying mechanism of tumour cytotoxicity. Synergistic ultrasound activation represents a promising development to Photodynamic Therapy, as photo-activation is limited by access and penetrance issues. Ultrasound has been demonstrated to activate a number of sono-sensitive agents allowing the possibility of non-invasive targeted treatment of deeper tumour sites than is currently achievable with photodynamic therapy. This case series of 17 consecutive patients with a variety of cancer diagnoses outlines clinical outcomes over a four-year period of SPDT. The results have been encouraging in that all cases who carried our Circulating Tumour Cell Tests before and after SPDT showed a significant drop in tumour cells post-SPDT. SPDT is worthy of further investigation as an effective and well tolerated treatment for a wide variety of primary and metastatic tumours, including those refractory to Chemotherapy.

Ex-Vivo Detection of Breast Cancer with a Bio-Impedance Sensor

Bioimpedance is the opposition to flow of an applied electrical current through biological tissues1. Our research group designed and fabricated bipolar micro-sensors on the tip of a silicone probe, capable of measuring biological tissue impedance. It is known that the bioimpedance of cultured cancer cells differs substantially from that of healthy cell lines. We hypothesised that the bioimpedance of cancer in surgically excised human tissue would be significantly different to surrounding healthy tissue. To test this hypothesis, we designed a study to evaluate the bioimpedance of healthy and diseased breast tissue in surgically excised breast specimens. This manuscript reports the outcome of this study.

Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Head and Neck Squamous Cell Carcinoma

Objectives: FDA approval of PD-L1 IHC 22C3 pharmDx for use as an aid in identifying head and neck squamous cell carcinoma (HNSCC) patients for treatment with pembrolizumab was based on the results of rigorous analytical and clinical validation testing. Methods: For the HNSCC indication, the device was validated at Agilent Technologies on the performance of sensitivity and precision using the Combined Positive Score (CPS) ≥ 1 and CPS ≥ 20 cutoffs; external validation studies were performed at three external laboratories. CPS ≥ 1 and CPS ≥ 20 cutoffs were evaluated in KEYNOTE-048, a phase 3 clinical trial. Results: Analytical validation studies supporting the companion diagnostic indication (CPS ≥ 1) achieved point estimates of > 85% for negative, positive, and overall percent agreement. Clinical validation studies show that HNSCC patients treated with pembrolizumab as a single agent had an overall survival (OS) of 12.3 months at CPS ≥ 1 (95% CI, 10.8-14.9) compared with patients receiving cetuximab, platinum, and 5-fluorouracil (CPS ≥ 1 OS of 10.3 months (95% CI, 9.0-11.5)). Conclusion: Analytical and clinical validation studies demonstrate that PD-L1 IHC 22C3 pharmDx is a precise companion diagnostic assay, allowing for selection of eligible HNSCC patients for treatment with pembrolizumab.

AP-2 Family of Transcription Factors: Critical Regulators of Human Development and Cancer

The AP-2 family of transcription factors consist of DNA-binding proteins: AP-2α to AP-2ε. Members and homologs of this family are also known in frogs, fish and invertebrates. These proteins have the same central basic region and a helix-span-helix dimerization motif, which is necessary for dimerization and DNA binding. This family have been found to influence facial, limbs and kidney development in embryogenesis while regulating differentiation and apoptosis. These proteins are also involved in regulation of endocrine processes. In addition to their influence on growth and development, this family have also been reported to correlate with tumorigenesis and development of cancer. At present, this family have been related to tumors of ovary, melanoma, lung, nasopharynx, breast, glioma, neuroblastoma, colon, etc. They regulate expression of many cancer-related genes and affect the occurrence, development, invasiveness and therapeutic response of cancers. Different expression levels of AP-2s are also related to different survival rate. These findings may bring new idea to the diagnosis, classification, treatment and prognosis of cancer.

Mini-Review: Recent Advances in Aptamer Applications

Aptamers, which are short strands of synthetic DNA or RNA selected for binding to target ligands, have proven useful for cell-specific delivery, detection, or both. This mini-review presents selected examples of these applications for cancer published during 2019 – September 2020.

Predictive Value of UGT1A1 Polymorphisms in Irinotecan-Induced Toxicity and Therapeutic Efficacy in Colorectal Cancer Patients

Irinotecan-based chemotherapy is a fundamental cytotoxic regimen for advanced colorectal cancer. The disposition of irinotecan is known to vary in a fashion partially depending on genetic variations in the drug metabolic pathways. UDP-glucuronosyltransferase (UGT)1A1 is a predominant enzyme that converts the active metabolite of irinotecan to the inactive form via a glucuronidation process. Several UGT1A1 polymorphisms are linked to SN-38 glucuronidation and irinotecan-related adverse events, while the predictive role of UGT1A1 polymorphisms regarding therapeutic outcome is controversial. In this review, we will evaluate the impact of UGT1A1 genotypes on irinotecan-induced toxicity and therapeutic efficacy in colorectal cancer patients receiving irinotecan-based treatment.