Journal of Carcinogenesis & Mutagenesis

The Oncogene Paradigm in Cancer Biology and Therapeutics

Chang Moo^* Department of Toxicology, Sun Yat-sen University, Guangzhou, China
^*Correspondence: Chang Moo, Department of Toxicology, Sun Yat-sen University, Guangzhou, China, Email:

Received: 30-Apr-2025, Manuscript No. JCM-25-29379; Editor assigned: 02-May-2025, Pre QC No. JCM-25-29379 (PQ); Reviewed: 16-May-2025, QC No. JCM-25-29379; Revised: 23-May-2025, Manuscript No. JCM-25-29379 (R); Published: 30-May-2025, DOI: 10.35248/2157-2518.25.S50.005

Description

Oncogenes are mutated or overexpressed versions of normal cellular genes known as proto-oncogenes, which play a key role in regulating cell growth, differentiation, and survival. When these genes undergo alterations, they can drive the uncontrolled cellular proliferation that is characteristic of cancer. The transformation of proto-oncogenes into oncogenes is a critical step in the multistep process of carcinogenesis and represents a fundamental concept in modern cancer biology [1].

The activation of oncogenes can occur through various mechanisms, including point mutations, chromosomal translocations, gene amplification, and insertional mutagenesis. One of the earliest discovered and most studied oncogenes is RAS, a gene family involved in signal transduction pathways that control cell growth and survival [2]. Mutations in RAS genes (HRAS, KRAS, and NRAS) lead to constitutive activation of signaling pathways such as MAPK and PI3K-AKT, contributing to malignant transformation. KRAS mutations, for instance, are prevalent in pancreatic, colorectal, and lung cancers and are often associated with poor prognosis.

Chromosomal translocations represent another significant mechanism for oncogene activation. The Philadelphia chromosome, resulting from a translocation between chromosomes 9 and 22, creates the BCR-ABL fusion gene, which encodes a constitutively active tyrosine kinase driving Chronic Myeloid Leukemia (CML). Targeted therapies like imatinib, which inhibit BCR-ABL, have revolutionized the treatment of CML, highlighting the therapeutic potential of understanding oncogene biology. Similarly, the MYC gene, often activated by translocations in Burkitt lymphoma, encodes a transcription factor that regulates a wide array of genes involved in cell cycle progression and metabolism [3-6].

Gene amplification can also lead to oncogene overexpression and tumor development. HER2/neu is a well-known example, amplified in approximately 20%-30% of breast cancers. The overexpression of HER2 leads to excessive signaling through receptor tyrosine kinase pathways, promoting cell proliferation and resistance to apoptosis. The development of HER2-targeted therapies such as trastuzumab has significantly improved outcomes in HER2-positive breast cancer patients, further supporting the role of oncogenes as therapeutic targets [7-9].

Beyond these classical oncogenes, advances in next-generation sequencing have uncovered a broader landscape of oncogenic drivers. Alterations in genes such as BRAF, EGFR, ALK, and PIK3CA are now recognized in various solid tumors, and many of these alterations can be targeted with specific inhibitors. For example, BRAF V600E mutations are common in melanoma and have led to the development of effective BRAF and MEK inhibitors that prolong survival in affected patients [10]. EGFR mutations, prevalent in non-small cell lung cancer, are responsive to tyrosine kinase inhibitors such as erlotinib and osimertinib, further demonstrating the clinical significance of oncogenes in personalized medicine.

In conclusion, oncogenes play a central role in the initiation and progression of cancer. Understanding their molecular mechanisms has not only deepened our knowledge of carcinogenesis but also paved the way for targeted therapeutic interventions. Continued research into the functions, interactions, and vulnerabilities of oncogenes remains essential for advancing cancer diagnostics and developing more effective, personalized treatment strategies. The integration of genomic data with clinical decision-making holds promise for transforming oncogene research into tangible benefits for cancer patients worldwide.

References

1. Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: A Review. JAMA Oncol. 2016;2(10):1346-53.

   [Crossref] [Google Scholar] [Pub Med]

2. Spain L, Diem S, Larkin J. Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev. 2016;44:51-60.

   [Crossref] [Google Scholar]

3. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450-61.

   [Crossref] [Google Scholar] [Pub Med]

4. Rizvi NA, Hellmann MD, Snyder A. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science. 2015;348(6230):124-128.

   [Crossref] [Google Scholar]

5. Robert C, Long GV, Brady B. Nivolumab in previously untreated melanoma without BRAF mutation. N Eng J Med. 2015;372(4):320-30.

   [Crossref] [Google Scholar] [Pub Med]

6. Le DT, Uram JN, Wang H. PD-1 blockade in tumors with mismatch-repair deficiency. N Eng J Med. 2015;372(26):2509-2520.

   [Crossref] [Google Scholar] [Pub Med]

7. Berghoff AS, Fuchs E, Ricken G. Density of tumor-infiltrating lymphocytes correlates with the extent of brain edema and overall survival time in patients with brain metastases. Oncoimmunology. 2016;5(1):e1057388.

   [Crossref] [Google Scholar] [Pub Med]

8. McGranahan N, Furness AJ, Rosenthal R. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463-1469.

   [Crossref] [Google Scholar] [Pub Med]

9. Jin Y, Dong H, Xia L. The diversity of gut microbiome is associated with favorable responses toanti-programmed death 1 immunotherapy in Chinese patients with NSCLC. J Thorac Oncol. 2019;14(8):1378-89.

   [Crossref] [Google Scholar] [Pub Med]

10. Li H, Bullock K, Gurjao C. Metabolomic adaptations and correlates of survival to immune checkpoint blockade. Nat Commun. 2019;10(1):1-6.

    [Crossref] [Google Scholar] [Pub Med]