Cross Talk between COVID-19 and Breast Cancer

Abstract

: Cancer patients are more susceptible for COVID-19; however, the prevalence of COVID-19 in different types of cancer is still inconsistent and inconclusive. Here, we delineate the intricate relationship between breast cancer and COVID-19. Breast cancer and COVID-19 share involvement of common comorbidities, hormonal signalling pathways, gender differences, rennin-angiotensin system (RAS), angiotensin-converting enzyme-2 (ACE-2), transmembrane protease serine 2 (TMPRSS2) and dipeptidyl peptidase-IV (DPP-IV). We also shed light on the possible effects of therapeutic modalities of COVID-19 on breast cancer outcomes. Briefly, we conclude that breast cancer patients are more susceptible for COVID-19 in comparison with their normal counterparts. Women are more resistant for the occurrence and severity of COVID-19. Increased expression of ACE2 and TMPRSS2 are being correlated with occurrence and severity of COVID-19, but higher expression of ACE2 and lower expression of TMPRSS2 are prognostic markers for overall and disease free survival in breast cancer. The ACE2 inhibitors and ibuprofen therapies for COVID-19 treatment may aggravate the clinical condition of the breast cancer patients through chemo-resistance and metastasis. Most of the available therapeutic modalities for COVID-19 were also found to exert positive effects on breast cancer outcomes. Besides drugs in clinical trend, TMPRSS2 inhibitors, estrogen supplementation, androgen deprivation and DPP-IV inhibitors may also be used to treat breast cancer patients infected with SARS-CoV-2. However, drug-drug interactions suggest that some of the drugs used for the treatment of COVID-19 may modulate the drug metabolism of anticancer therapies which may leads to adverse drug reaction events.

Predicting COVID-19—Comorbidity Pathway Crosstalk-Based Targets and Drugs: Towards Personalized COVID-19 Management

“…The treatment’s efficacy could be increased if the molecular pathway crosstalk between the specific comorbidity and COVID-19 is understood and that crosstalk-based targets and targeting drugs are used towards personalized medication. Although, some reports are available such as crosstalk between COVID-19 and breast cancer [ 24 , 25 ], COVID-19 and Alzheimer’s disease [ 26 ], COVID-19 and ischemic stroke [ 27 ], hyperthyroidism and COVID-19 [ 28 ], COVID-19 and age, and COVID-19 and hypertension [ 29 ]; omics-based molecular pathway crosstalk between COVID-19 and its associated vital comorbid conditions and those crosstalk-based targets have not been investigated.…”

Restructuring the ONYX-015 adenovirus by using spike protein genes from SARS-CoV-2 and MERS-CoV: Possible implications in breast cancer treatment

“…Most of the BC subtypes are being associated with mutations in BRCA1 and BRCA2; however, p53 mutations are associated with more aggressive disease outcomes and poor prognosis [2] . Besides, BC cells are shown to express ACE2, TMPRSS2, and DPP-IV [3] . However, most aggressive BC cells are known to be associated with the lower expression of ACE2 along with a concomitant increase in the expression of TMPRSS2 and DPP-IV [4] , [5] , [6] , [7] .…”

“…However, most aggressive BC cells are known to be associated with the lower expression of ACE2 along with a concomitant increase in the expression of TMPRSS2 and DPP-IV [4] , [5] , [6] , [7] . Here, it is interesting that ACE2 is the main receptor for the entry of SARS-CoV-2 via binding of viral spike protein (S) and TMPRSS2 contribute to the priming of S protein, whereas DPP-IV was thought to be a co-receptor for the entry of SARS-CoV-2 and the main receptor for MERS-CoV entry [3] . Last two decades witnessed the ONYX-015 oncolytic adenovirus therapy mainly for solid tumors.…”

“…In fact, ‘S’ protein of SARS-CoV-2 is involved into the cellular entry of virus through ACE2 receptors after priming by a protease enzyme TMPRSS2, whereas ‘S’ protein of MERS-CoV is responsible for its entry via DPP-IV receptors [3] . Here, it is noteworthy that DPP-IV is also thought to be a co receptor for the entry of SARS-CoV-2.…”

“…Here, it is noteworthy that DPP-IV is also thought to be a co receptor for the entry of SARS-CoV-2. It is pertinent that in most of the aggressive breast cancers lower expression of ACE2 and CAR were observed with the concomitantly increased expression of TMPRSS2 and DPP-IV [2] , [3] , [10] , [13] .…”