Impact of COVID-19 on cancer management in military hospitals of Saudi Arabia.

OBJECTIVES: To evaluate the impact of COVID-19 on cancer management in Saudi Arabia's military hospitals. METHODS: This multi-centric, retrospective study compared cancer patients diagnosed from February-July 2019 and 2020, focusing on the time duration for acceptance and time for oncologic treatment initiation. Eligibility and referral status were recorded. Clinical data of COVID-19-positive cancer patients were collected and evaluated their outcomes and survival. RESULTS: Data of 1574 cancer patients (mean age, 57.1 years) were collected. Mean time for acceptance was 7.3 days in 2019 and 8 days in 2020, with no statistically significant difference. Mean time for oncology treatment initiation was 38.4 days in 2019 and 44.3 days in 2020, with no statistically significant difference. The number of new cancer patients decreased in 2020 but increased in peripheral hospitals. It decreased in Riyadh and Jeddah hospitals. Concerning referral status, a statistically significant modification was recorded only in Riyadh and Tabuk hospitals. No significant changes observed in time duration for acceptance of new patients and oncology treatment initiation from 2019-2020. A total of 76 COVID-19-positive cancer patients recorded; 72% were symptomatic, 73.6% recovered, 22.3% died due to COVID-19 complications, and 8% died due to cancer; cancer progressed in 7 patients. CONCLUSION: COVID-19 did not affect oncology service in Saudi Arabia's military hospitals. New cancer cases reduced during the pandemic. Cancer patients are at increased risk for COVID-19 complications, including death.

Chemotherapeutic resistance of head and neck squamous cell carcinoma is mediated by EpCAM induction driven by IL-6/p62 associated Nrf2-antioxidant pathway activation.

Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines. We report that EpCAM was highly expressed in Nrf2-positive and HPV-negative HNSCC cells. In addition, cisplatin-resistant tumor cells consisted of a higher proportion of EpCAMhigh cells compared to the cisplatin sensitive counterpart. EpCAMhigh populations exhibited resistance to cisplatin, a higher efficiency in colony formation, sphere growth and invasion capacity, and demonstrated reduced reactive oxygen species (ROS) activity. Furthermore, Nrf2 expression was significantly higher in EpCAMhigh populations. Mechanistically, expression of Nrf2 and its target genes were most prominently observed in EpCAMhigh populations. Silencing of EpCAM expression resulted in the attenuation of expressions of Nrf2 and SOD1 concomitant with a reduction of Sox2 expression. On the other hand, silencing of Nrf2 expression rendered EpCAMhigh populations sensitive to cisplatin treatment accompanied by the inhibition of colony formation, sphere formation, and invasion efficiency and increased ROS activity. The molecular mechanistic link between EpCAM expression and activation of Nrf2 was found to be a concerted interaction of interleukin-6 (IL-6) and p62. Silencing of p62 expression in EpCAMhigh populations resulted in the attenuation of Nrf2 pathway activation suggesting that Nrf2 pathway activation promoted resistance to cisplatin in EpCAMhigh populations. We propose that therapeutic targeting the Nrf2-EpCAM axis might be an excellent approach to modulate stress resistance and thereby survival of HNSCC patients enriched in EpCAMhigh populations.