Abstract
Small cell lung cancer (SCLC) is known for its rapid growth with high metastatic spread. Its treatment remains a major challenge for oncologists due to the high mutation rate and other clinical disadvantages. The survival rate of these patients is very poor but there is no significant progress over the last few decades in the treatment protocols. Hence there is an urgency to design new clinical trials with novel drug combinations that can specifically and effectively target key pathways for proper treatment of SCLC. There have been several indications that developmental signalling pathways are involved in tumor growth, progression, metastasis and invasion of SCLC. Thus, it is anticipated that deciphering the signalling cascades of these embryonic signalling pathways may reveal novel therapeutic breakthroughs in SCLC. In this context, we have tried to assemble all the relevant information to give an updated overview of the various signalling pathways involved in the development of SCLC.
Highlights
Various developmental signalling pathways like Notch, hedgehog play an important role in cellular functions including cell motility, lineage, apoptosis, etc
This drug was specific for targeting NOTCH2 and NOTCH3 receptors, and its efficacy was analyzed in SCLC allografts followed by patient-derived xenografts (PDX) and in SCLC patients [34] (Fig. 1B)
Studies performed on the SCLC cell lines and tumors have reported the occurrence of high copy number gains (CNGs) in the FGFR1 cytogenetic bands [28, 73] which indicate the possibility of FGFR1 as a therapeutic target for SCLC [74]
Summary
For the last 15 years, there has been no improvement in survival rates and no new treatment has been approved. Though the majority of the SCLC patients are treated by chemotherapy and radiotherapy, a small number of patients undergo surgery to remove the tumor Since it requires robust materials for analyzing molecular profiling like genome or exome sequencing, the non-availability of tissues limits such study for SCLC. It is basically due to the lower mutational burden for the non-exposure of tobacco to the animal model These models are very costly and demand a great deal of time for the development of cancer. Resistance to chemotherapy: The majority of LDSCLC and ED-SCLC patients experience a relapse in just 6–12 months after completion of initial treatment Both the molecular mechanisms involved in the development of resistance and the chemoresistant properties of the cell population are yet to be discovered [15].
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