Over the past few decades, our understanding of cancer has shifted from viewing it as a single disease to recognizing it as a complex set of diseases driven by specific biological capabilities. In their seminal papers published in 2000, 2011, and updated again in 2022, Douglas Hanahan and Robert Weinberg proposed a conceptual framework known as the “Hallmarks of Cancer”, which describes the essential biological traits that cancer cells acquire during tumor development.

These hallmarks include properties such as sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. In 2011, additional hallmarks and enabling characteristics were added, such as reprogramming of energy metabolism and avoiding immune destruction. In the most recent 2022 update, Hanahan introduced further refinements, including phenotypic plasticity, nonmutational epigenetic reprogramming, polymorphic microbiomes, and influences from senescent cells. These hallmarks provide an organizing principle to understand how normal cells transform into malignant ones.

The Hallmarks of Cancer as conceptualized by Hanahan & Weinberg

Understanding these hallmarks has fundamentally shaped modern oncology by revealing the underlying mechanisms that drive cancer progression—and more importantly, it has paved the way for precision medicine. Instead of using traditional therapies that affect both healthy and cancerous cells, we now aim to design therapies that specifically target the aberrant pathways and immune escape mechanisms used by cancer cells.

This is where targeted therapy and immunotherapy come into play.

Targeted therapies are designed to interfere with specific molecules or signaling pathways that are crucial for cancer cell survival and proliferation

Linking Hallmarks to Therapies

Hallmark / Enabling Trait	Therapeutic Strategy	Examples
Sustaining proliferative signaling	Target growth-factor pathways	EGFR inhibitors, HER2 antibodies
Evading growth suppressors	Inhibit cell-cycle regulators	CDK4/6 inhibitors
Resisting cell death	Promote apoptosis	BCL-2 inhibitors
Inducing/accessing vasculature	Block angiogenesis	VEGF inhibitors
Deregulating metabolism	Disrupt tumor metabolism	Glycolysis inhibitors; metabolic modulators
Enabling replicative immortality	Target telomerase pathways (emerging)	Under clinical investigation
Avoiding immune destruction	Unleash T-cell response	Checkpoint inhibitors (PD-1, PD-L1, CTLA-4)
Unlocking phenotypic plasticity / Epigenetic reprogramming	Sensitize tumors to immune or targeted therapies	Emerging combination strategies
Genome instability / inflammation	Exploit DNA damage pathways	PARP inhibitors in BRCA-mutant cancers

Immunotherapies harness the patient’s own immune system to recognize and destroy cancer cells

5 Main Types of Cancer Immunotherapy

Type	Description	Examples
Immune Checkpoint Inhibitors	Block proteins (e.g., PD-1, CTLA-4) that restrain T-cells	Pembrolizumab (PD-1), Ipilimumab (CTLA-4)
CAR T-cell Therapy	Patient’s T cells are genetically modified to attack tumor cells	Tisagenlecleucel (CD19), Axicabtagene ciloleucel
Cancer Vaccines	Stimulate the immune system to target tumor-specific antigens	Sipuleucel-T for prostate cancer
Monoclonal Antibodies	Target tumor antigens or flag cells for destruction	Rituximab (CD20), Trastuzumab (HER2)
Cytokine Therapy	Use immune-stimulating proteins to boost immune response	IL-2, Interferon-α

Together, these therapies represent a paradigm shift—from a “one-size-fits-all” approach to personalized, mechanism-based treatments guided by the molecular and immunological hallmarks of each individual’s cancer.

References

• Hanahan D, Weinberg RA. Hallmarks of Cancer. Cell. 2000;100(1):57–70.
• Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell. 2011;144(5):646–74.
• Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discovery. 2022;12(1):31–46.