26 AACR Cancer Progress Report 2013
directly on cancer cells to drive their survival and division via
a signaling network called the PI3K/AKT/m TOR ( 46, 51, 52),
suggests that drugs targeting this pathway might be effective
in this context.
Any new therapeutic approaches developed in the future will
need to be used together with approaches to balancing energy
intake and output. For many people, modifying behaviors to
reduce calorie consumption and increase physical activity
may be sufficient, but other people may require surgical or
therapeutic interventions to help them lose weight. The urgent
need for an effective and comprehensive strategy is highlighted
by the fact that the number of Americans classified as obese is
at an all-time high. Currently, more than 35 percent of adults
and 17 percent of children and adolescents are obese ( 56).
Type 2 Diabetes Mellitus and Cancer
Type 2 diabetes mellitus is a complex medical condition caused
by a combination of factors, including obesity. Independent
of obesity, type 2 diabetes increases an individual’s risk of
developing cancer ( 57, 58). Those with type 2 diabetes are
most at risk for developing liver, pancreatic, and endometrial
cancers, but also have an increased risk for developing biliary
tract, bladder, breast, colorectal, esophageal, and kidney
cancers, as well as certain forms of lymphoma ( 58, 59).
Type 2 diabetes not only increases cancer risk, but also
reduces short- and long-term cancer survival rates through
both direct and indirect mechanisms ( 58). For example,
type 2 diabetes has been reported to have a direct negative
effect on tumor recurrence and survival in patients with colon
cancer ( 60). In general, survival for cancer patients with type
2 diabetes is worse than for their nondiabetic counterparts
because of indirect factors associated with diabetes. For
example, they are more likely to suffer from other potentially
fatal diseases, like heart disease, and to be poor candidates for
surgery and the highest doses of chemotherapy ( 58).
Despite the fact that type 2 diabetes affects about 7. 5 percent
of the U.S. population ( 61), it is not well established how type 2
diabetes increases cancer risk. Research suggests that it likely
influences cancer development in several ways, many of which
are similar to the ways in which obesity affects cancer ( 58,
59). For example, similar to obesity, type 2 diabetes increases
levels of insulin and causes persistent inflammation.
Importantly, recent evidence suggests that treatments directed
at reducing the hallmark of type 2 diabetes may influence
cancer risk. Metformin, which is one of the most commonly
used drugs for treating patients with type 2 diabetes, appears
to reduce a type 2 diabetic’s risk of developing colon and
pancreatic cancers ( 62, 63). In contrast, sulfonylureas,
a different class of drugs commonly used to treat type 2
diabetes, may increase risk of cancer development ( 58).
However, further studies are needed to clarify these issues
( 58). Given what we have learned about the anticancer effects
of metformin in patients with type 2 diabetes, numerous
clinical studies are underway to assess whether it has the
potential to benefit nondiabetic patients with cancer ( 64).
In light of the large number of Americans living with type
2 diabetes ( 61), it is critical for physicians managing these
patients to be keenly aware of their patients’ increased cancer
risks if we are to reduce the burden of cancer in this portion
of the population. Moreover, it is vital that we undertake more
research so that we better understand the biological pathways
linking the disease to cancer. Armed with this knowledge,
we can investigate potential new therapeutic approaches.
However, our best approach to reducing individuals’ risks
for type 2 diabetes and for certain forms of cancer, as well
as improving outcomes, is to combine any new therapeutic
approaches with behavior modifications, like eating a healthier
diet, increasing physical activity, and reducing calorie
Physical Activity and Cancer
A lack of regular physical activity (see sidebar on Physical
Activity Guidelines, p. 27) is strongly associated with an
increased risk for colon, endometrial, and postmenopausal
breast cancers, independent of weight ( 8). Mounting evidence
suggests that it may also be associated with lung, pancreatic,
and premenopausal breast cancers ( 8).
In addition, several recent studies indicate that sedentary
behavior may increase risk for developing certain cancers
and for mortality in cancer survivors independent of physical
activity and weight.
For example, one study showed that individuals who spent
10 or more years in sedentary work had almost twice the risk
of cancers arising in their rectum or in a specific part of their