Ever since its first eruption late last year, the number of COVID-19 has surged to millions around the world in a matter of a few months. The novel virus has claimed thousands of lives and is spreading fast and furious. For months now, experts around the world are working in harmony to find a solution for the deadly virus. One quick solution is maybe reworking the already existing antiviral drugs. However, it is not an easy task, due to an incomplete biological understanding of the virus and how the host cells react when encountered by it. 

To judiciously repurpose drugs, experts are working around the clock to understand the molecular process of the infection and the changes in the host to accommodate the viral replication. By finding the exact viral targets in the host cells, a potential drug can be selected for further testing to avoid patients from exposure to unnecessary drugs lacking validation. 

Growth Factor Receptor (GFR) is known to play a crucial role in many viral infections. The GFR signalling activation leads to a change in many cellular processes like adhesion, replication, and differentiation. In the past, various viruses like hepatitis C and influenza have shown to activate GFR signaling to replicate in the host cells. Currently, though COVID-19 is suspected to fall under the same category there is no solid evidence. The authors of this paper tried to establish that COVID-19 infections do activate GFR signaling which in turn aids in the viral replication process. While monitoring the above signalling changes in the host cells, the experts also observed that the activation of GFR signalling was consistent with other viruses relying on the receptors themselves. 

The study employed an in-vitro COVID-19 infection model replicating a human cell environment, to study the signalling changes within the host cell to accommodate viral replication. Well into the experiments the authors observed that the changes in the viral protein phosphorylation and phosphorylation driven host signalling was caused upon infection. Both the GFR signalling and downstream pathways were activated. 

On further experimentation, by performing drug-protein network analysis experts revealed that GFR signaling pathways is the key for viral replication. The GFR signalling further activates EGFR or PDGFR signalling with a profusion of RhoGTPase associated signalling molecules. 

The study does portray a few limitations. The authors had used cancer cells lines to study the virus in-vitro which does not completely speak for other cell lines. The kinetics of infection may be different for different cell lines and needs to be studied further. But taken together the results from the study provides potential novel insights into the molecular process of the viral infection. The proteomic analysis performed by the authors also revealed that several pathways are rearranged when the host cells are infected. By targeting these particular pathways a valid therapy can be found to inhibit the viral replication upon infection.

Small Cell Lung Cancer (SSLC) is a very particular lethal malignant cancer type for which effective therapies are urgently needed. Small cell carcinomas are usually centrally located, arising from the bronchus, with a small number of peripheral lesions. They obstruct most of the airways through circumferential compression. 

Around 15% of lung cancers are classified under SCLC. Recent studies indicate that SCLC can be split into 4 major subtypes, based on the expression YAP1, ASCL1, NEUROD1, or POU2F3. Treatments for these subtypes are not yet standardized, due to the lack of information on their physiology. 

Now scientists have summarised their new findings “MYC Drives Temporal Evolution of Small Cell Lung Cancer subtypes by reprogramming Neuroendocrine Fate” in Cancer Cell about the physiology of SCLC subtypes, which could potentially pave the way to study and treat the disease. 

Historically SCLC has been treated as a single disease. The disease exhibits genetic loss of tumor suppressors along with the expression of MYC, MYCL, or MYCN. Large scale gene expression analyses suggest that SCLC subtypes have distinct vulnerabilities which need to be understood to improve treatment. Subtype SCLC-ASCL1 which comprises 70% of the tumors is a regulator of neuroendocrine (NE) fate. Using genetically engineered mouse models (GEMM) it was found that ASCL1 is important for tumor development and that MYCL was highly expressed in this subtype. Contrastingly the other SCLC subtypes constituting 30% found to overexpress MYC and exciting low non-NE cell fate. Research shows that Myc expression drives a non-NE SCLC in GEMMs, however, the relationship between the subtypes SCLC-A and ACLC-N and involvement of MYC in driving other subtypes is still unknown. 

In this paper, the author and his team investigate MYC origins and its relationship with the SCLC subtypes. Functional data from the study suggest that MYC is behind the evolution of SCLC subtypes. In context to the times’ suppressor loss, MYC promotes temporal evolution from SCLC-A to SCLC-N to SCLC-Y in-vivo. The results from the study also revealed that MYC does not work alone and requires the help of the NOTCH signaling pathway to drive tumor progression. 

 The study further revealed that both MYCL and MYC are not functionally redundant in SCLC. They correlate with distinct gene expression and localize to super-enhancers. MYC and MYCL have the ability to change a cell morphology fate, molecular subtype, and influence drug sensitivity. 

Different SCLC subtypes inhibit different targeting drugs and considering this, dynamically evolving tumors are termed as moving therapeutic targets. Over the years many targeted therapies have failed to treat SCLC like chemotherapy. The authors of this study speculate that chemotherapy has remained the most effective due to its non-specificity among subtypes that evolve. The findings from these studies demonstrate that SCLC and other similar cancer types would benefit from a combination or customized therapies.

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