Cancer

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Cancer encompasses a wide range of diseases where cellular proliferation goes unchecked leading to increased cell growth and decreased cell death. Genetic alterations, which may be inherited or result from environmental influence, represent the main basic underlying mechanism for disease onset and progression. Accelerated growth, programmed cell death evasion, immune checkpoint evasion, and an ability to invade distant tissues are all hallmark properties of cancerous cells. These abnormal cellular properties are brought about by mutations in genes involved in the regulation of cell proliferation and growth, including proto-oncogenes and tumor suppressor genes. Additionally, mutations in genes involved in DNA repair further undermine the integrity of DNA sequences facilitating the accumulation of multiple DNA lesions in cancer cells.

Traditionally, cancer types have been identified based on the site of origin and afflicted organ or tissue. In the U.S., prostate and breast cancer represent the most prevalent cancer types afflicting males and females, respectively. It is also noteworthy that lung cancer causes ~25% of cancer-related deaths in both males and females. Lung cancer causes more deaths annually than breast, prostate, and colon cancer combined.

As cell proliferation plays a role in many physiological processes from embryonic development to the repair of damaged tissues, there are many mechanisms for keeping it under tight control. For instance, the activities of the proto-oncogenes are balanced by the actions of tumor suppressors. DNA damage and repair mechanisms exist to decrease the likelihood of genetic mutation and cell transformation. In addition, the immune system is designed to recognize and destroy cancerous cells. Accumulating disruptions in these homeostatic control mechanisms can lead to unregulated proliferation and cancer.

What are Tumor Suppressors?

Tumor suppressors are genes that protect cells from cancerous transformations. But, occasionally, these genes mutate and a loss in function leads to cancer. This is in contrast to oncogenes, which cause cancer through a mutation resulting in a gain of function. Tumor suppressor genes are often grouped into three categories: Caretakers, gatekeepers, and landscapers. Gatekeepers are those genes which prevent abnormal cell proliferation, caretakers provide genomic stability (through assessing and correcting DNA damage/mismatches/chromosomal abnormalities), and landscapers control the microenvironment in which cells grow.

p53 is often referred to as the “master” tumor suppressor gene because it is involved in the broadest of cancers. It can act as caretaker or gatekeeper and plays a role in apoptosis, genomic stability, and angiogenesis inhibition. There have been hundreds of other tumor suppressors reported and there continues to be new targets discovered through the field of oncogenomics. R&D Systems has an extensive catalog of tumor suppressor antibodies to suit most researchers needs.

What are Oncogenes?

Oncogenes are genes that are critical to the cause and proliferation of cancer. Normal, non-mutated forms of these genes (proto-oncogenes) code for proteins that regulate cell growth and differentiation. In contrast to tumor suppressors, they are involved in cancer through a gain of function, not loss of function (caused by a mutation, increased expression, or chromosome rearrangement). Many current cancer therapies focus on targeting proteins that are encoded by oncogenes.

There are many known and proposed mechanisms of oncogenesis, which can lead to abnormal cell growth. Some well-studied drivers of malignancy include mutation of proteins involved in intracellular signaling (such as MAPK/ERK and PI3K/Akt/mTOR pathways), mutation of growth factor receptors (ex. PDGF), and excess expression of growth factors (ex. ErbB2/HER2).

Select References For Further Reading

1. Aoki, K., & Taketo, M. M. (2007). Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. Journal of Cell Science. https://doi.org/10.1242/jcs.03485
2. Fuhrman-Luck, R. A., Loessner, D., & Clements, J. A. (2014). Kallikrein-Related Peptidases in Prostate Cancer: From Molecular Function to Clinical Application. EJIFCC. PMCID: PMC4975200
3. Goldar, S., Khaniani, M. S., Derakhshan, S. M., & Baradaran, B. (2015). Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pacific Journal of Cancer Prevention. https://doi.org/10.7314/APJCP.2015.16.6.2129
4. Hassanpour, S. H., & Dehghani, M. (2017). Review of cancer from perspective of molecular. Journal of Cancer Research and Practice. https://doi.org/10.1016/j.jcrpr.2017.07.001
5. Jaiswal, P. K., Goel, A., & Mittal, R. D. (2015). Survivin: A molecular biomarker in cancer. Indian Journal of Medical Research. https://doi.org/10.4103/0971-5916.159250 
6. Maguer-Satta, V., Besançon, R., & Bachelard-Cascales, E. (2011). Concise review: Neutral endopeptidase (CD10): A multifaceted environment actor in stem cells, physiological mechanisms, and cancer. Stem Cells. https://doi.org/10.1002/stem.592
7. Sau, A., Lau, R., Cabrita, M. A., Nolan, E., Crooks, P. A., Visvader, J. E., & Pratt, M. A. C. (2016). Persistent Activation of NF-κB in BRCA1-Deficient Mammary Progenitors Drives Aberrant Proliferation and Accumulation of DNA Damage. Cell Stem Cell. https://doi.org/10.1016/j.stem.2016.05.003
8. Yang, D., Wu, Z., Duan, H., Luo, Y., Lu, D., Li, W., … Yan, X. (2011). CD146, an epithelial-mesenchymal transition inducer, is associated with triple-negative breast cancer. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1111053108
9. Zamay, T. N., Zamay, G. S., Kolovskaya, O. S., Zukov, R. A., Petrova, M. M., Gargaun, A., … Kichkailo, A. S. (2017). Current and prospective protein biomarkers of lung cancer. Cancers. https://doi.org/10.3390/cancers9110155