49
sensors, transducers, and effectors. The proteins ATR and ATM are the main transducer of DNA damage. ATR responds to a broad spectrum of DNA damage, including DSBs and a variety of DNA lesions that interfere with replication. ATR is the
main transducer after UV radiation and Chk1 is its downstream transducer. Chk1 is
exclusively associated to the maintenance of active DNA synthesis after UV radiation in a manner in which Chk1 release from DNA molecule prompts TLS to avoid
replication stalling (Speroni et al. 2012). On the other hand, ATM is primarily activated by DSBs being Chk2 and p53 its principal effectors. p53 gene is one of the
most frequently mutated gene in human tumors and especially in skin cancers like
SCC, BCC, and precancerous tissues. Convincing models for the initial steps of UV
carcinogenesis, especially for SCC, already exist, based on findings that p53 mutations in NMSC are detected at higher frequency (50–90%) (Benjamin and
Ananthaswamy 2007).
4.2.3 Markers for Skin Cancer Diagnostic, Progression,
and Treatment
With rates of skin cancer rising in many parts of the world, SDG Target 3.4 “by
2030, reduce by one third premature mortality from non-communicable diseases
through prevention and treatment and promote mental health and well-being” is
ever more salient. As it is known that early stages of skin cancer can be cured with
good prognosis, skin cancer can be treated by means of secondary prevention as
well as tertiary prevention, which already includes therapy and rehabilitation
(Greinert 2009). The more sensitive and accurate the diagnostics and treatments, the
better results can be observed.
Traditional epidemiology uses environmental and/or lifestyle factors as markers
to evaluate the risk of some diseases or the early detection of them. For skin cancer,
the duration of exposure to sun, intensity, frequency, age at exposure’s time, skin
type, and number of nevi are considered important factors to evaluate the potential
risk of disease development (Greinert 2009). But these methods are often biased by
subjective failures to remember exact time points of appearance of, for example,
preclinical symptoms of a disease, individual behavior in the environment, and
other individual components of lifestyle (Greinert 2009). While these factors have
been used for a long time and they are already quite specific, they lack the precision
to find biological plausibility as an important criterion to assigning causality
(Greinert 2009). Thus, these markers are not the ideal tools for increasing test’s
sensitivity and specificity on the early detection stages.
In order to design better diagnosis tests and treatments, it is extremely necessary
to use “more objective” markers. In 1998, the National Institute of Health Biomarkers
Definitions Working Group defined a biological marker or biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic
intervention.” In the last 25 years, the epidemiology area has incorporated new tools
4 SDG 3 Good Health and Well-Being
sensors, transducers, and effectors. The proteins ATR and ATM are the main transducer of DNA damage. ATR responds to a broad spectrum of DNA damage, including DSBs and a variety of DNA lesions that interfere with replication. ATR is the
main transducer after UV radiation and Chk1 is its downstream transducer. Chk1 is
exclusively associated to the maintenance of active DNA synthesis after UV radiation in a manner in which Chk1 release from DNA molecule prompts TLS to avoid
replication stalling (Speroni et al. 2012). On the other hand, ATM is primarily activated by DSBs being Chk2 and p53 its principal effectors. p53 gene is one of the
most frequently mutated gene in human tumors and especially in skin cancers like
SCC, BCC, and precancerous tissues. Convincing models for the initial steps of UV
carcinogenesis, especially for SCC, already exist, based on findings that p53 mutations in NMSC are detected at higher frequency (50–90%) (Benjamin and
Ananthaswamy 2007).
4.2.3 Markers for Skin Cancer Diagnostic, Progression,
and Treatment
With rates of skin cancer rising in many parts of the world, SDG Target 3.4 “by
2030, reduce by one third premature mortality from non-communicable diseases
through prevention and treatment and promote mental health and well-being” is
ever more salient. As it is known that early stages of skin cancer can be cured with
good prognosis, skin cancer can be treated by means of secondary prevention as
well as tertiary prevention, which already includes therapy and rehabilitation
(Greinert 2009). The more sensitive and accurate the diagnostics and treatments, the
better results can be observed.
Traditional epidemiology uses environmental and/or lifestyle factors as markers
to evaluate the risk of some diseases or the early detection of them. For skin cancer,
the duration of exposure to sun, intensity, frequency, age at exposure’s time, skin
type, and number of nevi are considered important factors to evaluate the potential
risk of disease development (Greinert 2009). But these methods are often biased by
subjective failures to remember exact time points of appearance of, for example,
preclinical symptoms of a disease, individual behavior in the environment, and
other individual components of lifestyle (Greinert 2009). While these factors have
been used for a long time and they are already quite specific, they lack the precision
to find biological plausibility as an important criterion to assigning causality
(Greinert 2009). Thus, these markers are not the ideal tools for increasing test’s
sensitivity and specificity on the early detection stages.
In order to design better diagnosis tests and treatments, it is extremely necessary
to use “more objective” markers. In 1998, the National Institute of Health Biomarkers
Definitions Working Group defined a biological marker or biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic
intervention.” In the last 25 years, the epidemiology area has incorporated new tools
4 SDG 3 Good Health and Well-Being