Cancer Research
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Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other body parts. Cancer can start almost anywhere in the human body, consisting of trillions of cells. The cancerous cells can invade and destroy surrounding healthy tissue, including organs. Each year, approximately 400,000 children develop cancer. The most common cancers vary between countries. Cervical cancer is the most common in 23 countries.
- Lung Cancer
Most cancers that start in the lung, known as primary lung cancers, are carcinomas. The two main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). The most common symptoms are coughing (including coughing up blood), weight loss, shortness of breath, and chest pains.
Fig.1 A schematic diagram of lung structures. (May, et al., 2019)
- Colorectal Cancer
Colorectal Cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death. The CRC is attributable to environmental risk factors including alcohol drinking, smoking, and inflammatory bowel disease. Inactivation of the tumor suppressor genes such as APC, and TP53 are critically important for CRC development.
Fig.2 Stages of colorectal cancer. (Nishu, et al., 2020)
- Liver Cancer
Liver cancer is only one of the top five deadliest cancers to have an annual percentage increase in occurrence. Developing counties have more incidence of liver diseases. Risk factors include hepatitis B virus, hepatitis C virus, fatty liver disease, alcohol-related cirrhosis, smoking, diabetes, and various dietary exposures. The two major types of primary liver cancer (PLC) – that is, hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) – comprise more than 1 million newly diagnosed cases per year.
Fig.3 Sequential evolution of PLC. (Jens, et al., 2015)
Membrane Proteins in Cancer Research
- Epidermal Growth Factor Receptor (EGFR)
The EGFR gene is located on the short arm of chromosome 7 and encodes a 170-kDa type I transmembrane growth factor receptor with TK (Tyrosine Kinase) activity. It transduces important growth factor signaling from the extracellular milieu to the cell. EGFR has become an important therapeutic target for the treatment of NSCLCs, HCC, CCA, and EGFR-expressing, RAS wild-type metastatic colorectal cancers. Inhibitors that target the kinase domain of EGFR have been developed and are clinically active.
Fig.4 The EGFR pathway in NSCLCs. (Ping, et al., 2019)
- Programmed Death-1 (PD-1)
PD-1 is an inhibitory receptor from the CD28 family that is expressed on various immune cells including T and B lymphocytes, dendritic cells (DCs), monocytes, and macrophages. While PD-1 is not expressed on naïve T cells, it is upregulated following T cell receptor (TCR)-mediated activation and readily observed on both activated and exhausted T cells. These "exhausted" T cells have a dysfunctional phenotype and are unable to appropriately respond to stimuli. Although there is a relatively wide expression pattern for PD-1, its most important role is likely as a coinhibitory receptor on T cells. Current therapeutic approaches focus on blocking the interaction of this receptor with its ligands to enhance T cell responses to treat cancers.
Fig.5 PD-1/PD-L1 immune checkpoint in NSCLC. (Ping, et al., 2019)
Fig.6 PD-1/PD-L1 immune checkpoint in HCC cells. (David, et al., 2020)
- C-X-C Chemokine Receptors
Chemokines are an important class of cytokines with major roles in regulating tumor microenvironment (TME) and resistance to cancer treatment. Chemokine receptors have their N-terminus outside the cell and the C-terminus in the cytoplasm. Based on their chemokine ligands, chemokine receptors are divided into two subfamilies: conventional chemokine receptors (cCKR) and atypical chemokine receptors (ACKR). CXCL12-CXCR4/CXCR7 axis is involved in survival, tumor growth angiogenesis, metastasis, TME, and drug resistance. it is considered a promising target for therapeutic intervention.
Fig.7 A schematic of the CXCL12/CXCR4/CXCR7 signaling pathways. (Yi, et al., 2020)
- Vascular Endothelial Growth Factor Receptor (VEGFR)
Blood vessels are required for the growth and dissemination of a solid tumor. There are numerous growth factors involved in tumor angiogenesis, but foremost among them is the family of VEGFs. These family proteins are ligands that can bind with different affinities to three endothelial receptor tyrosine kinases (RTKs), such as VEGFR1, VEGFR2, and VEGFR3. VEGF and VEGFR are also immunosuppressives, which makes them therapeutic targets for restoring antitumor immunity.
Fig.8 Effects of VEGF on immune cells. (Ju, et al., 2018)
References
- May, P.H.; et al. Automatic Detection and Staging of Lung Tumors using Locational Features and Double-Staged Classifications. Applied Sciences. 2019, 9: 2329
- Nishu, D.; et al. Omics technology for improved diagnosis and treatment of colorectal cancer: Technical advancement and major perspectives. Biomedicine & pharmacotherapy. 2020: 131.
- Jens, U.; et al. Functional and genetic deconstruction of the cellular origin in liver cancer. Nature Reviews Cancer. 2015, 15: 653-667.
- Ping, C.H.; et al. Epidermal Growth Factor Receptor (EGFR) Pathway, Yes-Associated Protein (YAP) and the Regulation of Programmed Death-Ligand 1 (PD-L1) in Non-Small Cell Lung Cancer (NSCLC). International Journal of Molecular Sciences. 2019, 20(15): 3821
- David, A.; et al. Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta Rev Cancer. 2020, 1873(1): 188314.
- Yi, S.; et al. The Role of the CXCL12/CXCR4/CXCR7 Chemokine Axis in Cancer. Frontiers in Pharmacology. 2020, 11: 574667.
- Ju, Y.; et al. Targeting VEGF/VEGFR to Modulate Antitumor Immunity. Frontiers in Immunology. 2018, 9: 978
