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Researching the Underlying

Causes of Cancer

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MOLECULAR CAUSES OF CANCER

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Through a deep commitment to science, Genentech is dedicated to defining
the molecular basis of cancer. Although there is a great amount of
complexity in cancer, cancer cells exhibit distinct attributes across tumor
types that enable them to grow and metastasize to distant organs.1
 Based on decades of cumulative preclinical knowledge and evidence-based
analyses, leading scientists finally came up with a logical framework to
identify the 6 hallmark features that distinguish a tumor cell from its
nonmalignant counterpart. This happened in the year 2000. Over the years,
these foundational hallmarks have helped the oncology community
appreciate the underlying biological principles operating in a tumor cell. 1
However, recent studies have identified 2 additional hallmark features and 2
enabling characteristics that aid in the carcinogenic process. Collectively,
these hallmark features provide a broad mechanistic framework within which
the multistep transformation of a premalignant cell to its lethal metastatic
counterpart is understood.1

Click on a hallmark of cancer below to learn more

Activating invasion and metastasis
Enabling replicative immortality
Evading growth suppressors
Evading immune destruction
Immune surveillance is an essential cellular process that pro-actively
prevents tumor formation in the human body. Preclinical studies have
suggested that an active immune system continuously recognizes and
eliminates the vast majority of cancer cells before they establish themselves
and form a tumor mass.1,2
However, cancer immuno-editing, an emerging hallmark, includes 3 key
phaseselimination, equilibrium, and escape.3

The immune system successfully recognizes and eliminates cancer

cells, a process often described as the elimination phase

Tumor cells not eliminated by the immune system proceed to the

equilibrium phase, in which the immune system controls cancer cell
growth but does not completely eliminate the transformed cells

Tumor cells not susceptible to immune destruction progress into the

escape phase. In this phase, the escaped tumor clonesnot effectively
detected and destroyed by the immune systemcontinue to divide and
grow

Clinical examples also support this finding, demonstrating that colorectal and
ovarian cancer patients with an increased immune response have a better
prognosis than do those patients with a reduced immune response.1
Figure 4. Evading immune destruction4,5
 Cancer immuno-editing, an emerging hallmark, comprises 3 key phases
elimination, equilibrium, and escape. Cancer cells that successfully navigate
these phases acquire the ability to evade immune destruction. 4

References
1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next
generation. Cell. 2011;144:646-674. PMID: 21376230
2. Vajdic CM, van Leeuwen MT. Cancer incidence and risk factors after
solid organ transplantation. Int J Cancer. 2009;125:1747-1754. PMID:
19444916
3. Teng MW, Swann JB, Koebel CM, Schreiber RD, Smyth MJ. Immune-
mediated dormancy: an equilibrium with cancer. J Leukoc Biol.
2008;84:988-993. PMID: 18515327
4. Prendergast GC. Immune escape as a fundamental trait of cancer:
focus on IDO. Oncogene. 2008;27:3889-3900. PMID: 18317452
5. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer
immunoediting. Nat Rev Immunol. 2006;6:836-848. PMID: 17063185
Genome instability and mutation
Inducing angiogenesis
Reprogramming energy metabolism
Evading cell death
Sustaining proliferative signaling
Tumor-promoting inflammation

References
1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next
generation. Cell. 2011;144:646-674. PMID: 21376230

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