Cancer is characterized by the abnormal division of cells, leading to uncontrolled growth and invasion of surrounding tissues. It originates from a single cell due to mutations and the loss of normal control. Beyond mere uncontrolled cell division, cancer is a progressive process involving genetic changes. Each of these changes confers a growth advantage, ultimately transforming normal cells into cancerous ones [1].
Types of Cancer:
Certain cancers are benign, closely resembling normal cells and remaining localized in small sizes. Although they may not pose an immediate threat, problems can arise if they interfere with normal functions or secrete excessive active substances. On the other hand, malignant cancers exhibit rapid growth and division, expressing proteins characteristic of their tissue of origin. They have the ability to invade surrounding tissues, enter the circulatory system, and proliferate at sites distant from their point of origin. The primary distinction between benign and malignant tumors lies in their invasiveness and capacity to spread [1].
Essential changes at cell level and six Hallmarks of Cancer:
A group of researchers has delineated six fundamental changes in cell physiology crucial for the progression of cells toward malignancy. Here are the six hallmarks of cancer as outlined by the group of researchers and some of the examples [2].
Insensitivity to Anti-growth Signals: Involves mutations in cell cycle regulators like retinoblastoma protein and p53. These regulators block individual cell progression in the presence of issues.
Self-sufficient Growth Signals: Arises from a single-point mutation in RAS. Leads to the production of an oncoprotein that inefficiently hydrolyzes GTP to GDP and stay activated.
Bypassing Apoptosis: Results from the loss of tumor suppression gene function (e.g., TP53). Alternatively, an increase in antiapoptotic regulation (e.g., Bcl-2 family).
Induced Angiogenesis: Orchestrated by the hypoxia-inducible transcription factor (released when low oxygen) and causes production of VEGF, which Prompts replication of endothelial cells and pericytes, forming new blood vessels to supply nutrients to the tumor.
Limitless Replicative Potential: Involves increasing telomerase enzyme activity. Stabilizes the chromosome, providing cells with limitless replicative potential.
Tissue Invasion: Marked by epithelial-mesenchymal transition. Causes the loss of cell-cell adhesion and interactions with the extracellular matrix. Release of proteases contributes to the breakdown of cell barriers, initiating metastasis.
It’s noteworthy that the order in which these changes occur varies across different types of cancer.
Additional Hallmarks of Cancer [3]
Immune Evasion: Employ strategies such as release immunosuppressive factors, recruit immune suppressive cells, and produce proteins to deactivate antigen-presenting cells to evade the immune system.
Deregulation of Cellular Energetics: Shifting the cellular energy dynamics by predominantly relying on glycolysis (85%) to produce lactate and utilizing oxidative phosphorylation minimally (5%) to meet energy demands and synthesize oxidized biomolecules.
Tumor-Promoting Inflammation: Triggering inflammation through various means, including chronic infections, dietary factors, environmental influences, and therapeutic interventions.
Genome Instability: Introducing genome instability through mutations in key genes like BRCA1 and BRCA2, which play a central role in DNA repair processes.
These factors, in conjunction with the previously mentioned hallmarks, contribute to the multifaceted nature of cancer development and progression.
Furthermore, recent advancements have unveiled additional cancer hallmarks, including non-mutational epigenetic reprogramming marked by histone modification and changes in DNA methylation. Other emerging hallmarks involve unlocking phenotypic plasticity, polymorphic microbiomes, and the presence of senescent cells. Targeting these newly identified cancer hallmarks through therapeutic interventions holds the potential to disrupt tumor growth and progression [4].
Potential drug-based therapies encompass telomerase inhibitors, selective anti-inflammatory drugs, inhibitors of angiogenesis, and immune-activating agents such as anti-CTLA4 monoclonal antibodies. These strategies offer promising avenues for combating cancer by addressing the intricate mechanisms associated with its development and progression.
References:
- Lodish et al., Molecular Biology of the Cell 6th Edition
- Hanahan and Weinberg, Cell 100:57-70
- Hanahan and Weinberg, Cell 144:646-74
- Hallmarks of Cancer: New Dimensions
Very informative article. Keep it up