Current concepts in the pathogenesis of cancer /certified fixed orthodontic courses by Indian dental academy
Current concepts in Pathogenesis
INDIAN DENTAL ACADEMY
Leader in continuing dental education
History : Egypt 3000 to 1500 B.C
Head and neck cancer : sixth most common cancer worldwide.
Increased incidence in developing countries.
“ There is tremendous literature on cancer ,but what we know for
sure about it can be printed on a calling card”
Familial / sporadic
Tissue of origin
Benign / malignant
Degree of differentiation
Local increase in cell number
Loss of normal arrangements of cell
Variation of cell size and shape
Increase in nuclear size and density
Increase in mitotic activity
Decreased interaction between cells
Invasion and metstasis
Cancer is a gentic disorder at the cellular level
Benign and Malignant cell
Nickel & chromate dust
Hard wood dust.
>7 cigrattes / day – 2.4 relative risk .
>25 cigrattes / day – 16.4
Cessation - 70% reduction after 10 years.
Smoking – 33%
Smoking +alcohol – 58%
Neither – 17%
Alcohol : 13 YRS STUDY IN 28180 PTS.
Beer / spirits – RR 3.0
With wine – RR 0.5
Henderson; Ross; Pike;-1991. Cancer science.
Towards the primary prevention of
cancer.primary prevention of cancer. 254, 1131
“High consumption of dietary fat is linked with
breast , prostate, ovarian cancer”.
“Diet low in fiber is associated with colon
“Vitamin C and E exert a protective effect by
decreasing the formation of carcinogenic
Initiators & promoter
1.Single exposure to alter cell
High doses carcinogenic
2.contact after initiator
Reversible in early stages
Needs prolonged exposure
No metabolic conversion
Principle of carcinogenesis
Study by berenblum
In skin cancer
Promoter: croton oil
It applies only to chemicals
Egs. of promoter benzopyrene
PATHOPHYSIOLOGY : The cell cycle
P53 Gene :Apoptosis
Guardian of the genome
Tumor suppressor gene
G1 – G0.
Inactivated by Mdm 2
Depends on both int. and external cell signals..
activation of caspases
Monoclonal antibody therapy.
Activates death receptors in tumor cells.
Chemo + apoptotic drugs - synergistic
Drugs Trastuzumab and rituximab are under
Draw back : drug resistance
COX 2 levels are elevated in certain cancers
Clinical data: pts under cox inhibitors have
decreased colon cancer
Recent advances in tumor angiogenesis
On June 20, 2006, the FDA granted approval for a
labeling extension for bevacizumab (Avastin®)
administered in combination with intravenous 5fluorouracil-based chemotherapy, for the secondline treatment of metastatic carcinoma of the colon
Patients treated with the Avastin combination
were reported by investigator assessment to have
significantly longer progression-free survival and
higher overall response rate.
Recent advances in cancer biology
The New England Journal of Medicine, Feb. 9, 2006
Cetuximab (Erbitux®) Plus Radiation Beneficial for Patients
with Head and Neck Cancer
Between 1999 and 2002, a total of 424 patients with stage III
or IV head and neck cancer
The median duration of locoregional control was 24.4 months
with the combined therapy and 14.9 months for radiation
patients on the combined therapy saw their risk of death cut
by 26 percent compared to the radiation-only group
Journal of Clinical Oncology, Nov. 20, 2005
Oxaliplatin (Eloxatin®) Plus Radiation Superior in
Advanced Nasopharyngeal Cancer
Oxaliplatin is a newer platinum-based drug that
has fewer side effects than cisplatin
Patients who were treated with radiation plus
oxaliplatin did significantly better than those
receiving radiation alone. None of the patients
getting chemoradiotherapy had died after two
years, compared to a survival rate of 77 percent for
those getting radiation alone
chemo + Rad – 17%
Only Rad – 4%
Proteomics & Cancer
Refers to the study of the proteins. Because proteins are
involved in almost all biological activities, the proteome is a
rich source of biological information.
Age – 12 yrs.
A $104 million program.
5,00,000 cellular proteins
Future: Bio markers - Nanotechnology – A.I
Biology therapy / Immunotherapy
Biological therapies use the body’s immune system to fight
cancer or to lessen the side effects that may be caused by
some cancer treatments
Biological response modifiers
The U.S. Food and Drug Administration (FDA) has approved
the use of interferon alpha for the treatment of certain types
Tailor made treatment – heterogenicity.
Nutrition and Cancer
The journal Mechanisms of Ageing and Development
Arthur B. Robinson, Oregon Institute of Science and
Medicine, December 1999
Excellent nutrition strengthens the immune system and
other defense mechanisms
But,once cancer has established itself, excellent nutrition
leads to its accelerated growth.
Linus Pauling Institute of Science and Medicine.
vitamin C in ordinary doses accelerated the growth rate of
squamous cell carcinoma in mice.
1-5gms / 100 gms
Ann Wigmore's establishment for diet
The CARET study trial
The Beta Carotene and Retinol Efficacy Trial
The purpose of the study was to test whether a
beta carotene supplement reduced the risk of
A 12 year study
In the Alpha-Tocopherol, Beta-Carotene Cancer
Prevention Trial, 18 percent more lung cancers
were diagnosed and 8 percent more overall deaths
occurred in study participants taking beta