Lung Cancer: Pathophysiology, Treatment with Cisplatin, and Adverse Effects

This presentation provides an overview of the pathophysiology of lung cancer, focusing on the dysplasia of lung epithelium and genetic mutations. It also discusses the pharmacology of treatment with cisplatin, including its mechanism of action and the formation of DNA adducts. Additionally, the adverse effects of cisplatin, such as renal toxicity and cardiotoxicity, are explored. The presentation concludes with the relevance of exercise in lung cancer management.

Lung Cancer
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Lungs are the chief respiratory system’s organs.
They are responsible for performing gaseous
exchange.
A network of bronchi and bronchioles help in
transportation of inhaled air and substances to
the alveoli.
In the bronchi, there are putative stem cells,
which are the basal cells, and produce the
differentiated neuroendocrine, ciliated, and
mucous cells.
Upon reaching the alveoli oxygen is absorbed
from the air and it is passed into the blood for
circulation throughout the body.
On the other hand, carbon (iv) oxide is passed
from the blood into the alveoli and is expelled
through breathing out.
The lungs are also involved in defending the
body against harmful materials such as smoke,
microorganisms, and smoke.
These materials are trapped into mucus, a thick,
slippery fluid, and cilia helps to push the mucus
up the bronchi to be removed through
swallowing or coughing.
Introduction
Normal Physiology of Lungs

 The pathophysiology of lung cancer is
intricate.
 Constant exposure to carcinogens results to
dysplasia of lung epithelium (Siddiqui &
Siddiqui, 2019).
 Genetic mutation and subsequent alteration of
protein syntheis can occur.
 Cell cycle is then disrupted and carcinogenesis
is promoted .
 Types of lung cancer
◦ small cell lung cancer and
◦ non-small cell lung cancer
 Often, genetic mutations in proto-oncogenes
such as MYC, p53, and BCL2 lead to small cell
lung cancer
 Mutations in KRAS, EGFR and p16 lead to non-
small cell lung cancer
 Often, mutations on EGFR halts
◦ regulate apoptosis,
◦ normal proliferation of cells, and
◦ other cellular functions (Lemjabbar-Alaoui, Hassan,
Yang, & Buchanan, 2015)
 Lung cancer can also occur from
◦ structural reorganization of ALK (Anaplastic
Lymphoma Kinase) and ROS1
◦ amplification of proto-oncogenes
◦ oncogenic overexpression of gene by microRNAs
◦ inactivation of tumor suppressor genes
Pathophysiology of Lung Cancer

 The most common drugs used for chemotherapy include
◦ carboplatin, and
◦ docetaxel for chemotherapy
 Cisplatin is a common and effective drug (Dasari & Tchounwou, 2014).
 It has a strong antitumor activity
 Once it enters the cell, it becomes activated and its chloride atoms are replaced by
water molecules in the cytoplasm
 The resulting solution is a strong electrophile with the capability of reacting with
nucleic acids’ nitrogen donor atoms and proteins’ sulfhydryl groups
 Cisplatin combines with N7 reactive center on residues of purines causing damage to
DNA’s cancer cells
 Thus, the mechanism of action of this drug is linked to its aptitude to crosslink with
DNA’s urine bases to form DNA adducts (Aldossarry, 2019).
 As a result, the following occurs subsequently
◦ cell cycle is arrested
◦ cell division blocked
◦ DNA repair is prevented
◦ as DNA damage persists apoptosis within cancer cells is induced (Aldossarry, 2019).
 The impairment of replication of DNA in cancer cells leads to death of the carcinogenic
cells
Pharmacology of Treatment
with Cisplatin

 Cisplatin has certain adverse and side effects
 The adverse effects of this drug include
◦ renal toxicity,
◦ ototoxicity,
◦ myelosuppression,
◦ vomiting, anaphylaxis, and
◦ nausea
cardiotoxicity resulting in
 myocarditis,
 congestive heart failure,
 electro-cardioghraphicchanges, and
 arrhythmias (Dasari & Tchounwou, 2014).
 Fundamental alterations in the toxicity of cisplatin leads to a reduction in
antioxidant defense system due to oxidative stress that arises from release
of reactive oxygen species
 To prevent renal toxicity the quantity of urine ought to be assessed.
 Also, huge dosage infusion is obligatory in chemotherapy where cisplatin is
used (Dasari & Tchounwou, 2014).
Adverse and Side Effects of
Cisplatin

 Cisplatin is administered intravenously as an infusion.
 It may be used in combination with paclitaxel (PDR, n.d.).
 It may also be used in combination with docetaxel (PDR,
n.d.).
 Precautions and contraindications
◦ It should not be administered to persons with a history of severe
allergic reactions platinum containing formulations
◦ it should not be administered together with aspirin,
◦ it affects patient’s fertility, and
◦ patients should not be immunized or vaccinated during the period of
administration
◦ Affects pregnancy and lactation
◦ severe myelosuppression,
◦ hearing impairment, and
◦ renal impairment (PDR, n.d.).
Cisplatin Administration,
Precautions, and Contraindications

◦ An exercise program is a
coping strategy to physical
and emotional impacts of lung
cancer (Michaels, 2016).
◦ Additionally, a preoperative
exercise program can also be
advised before curative lung
surgery as it has been shown
to improve outcomes
◦ Exercise can be beneficial for
individuals with lung cancer by
 increasing endurance
 Increasing strength, and
 decreasing emotional issues
(Michaels, 2016)
Relevance to Sport
Exercise

 Lungs are the chief respiratory system’s organs.
 They are responsible for performing gaseous exchange.
 The two main types of lung cancer are small cell lung cancer and non-small cell lung
cancer
 In most cases lung cancer occurs when a carcinogen such as cigarette induces
growth of abnormal cells in the lungs.
 The cells replicate continuously forming a tumor
 Different drugs are used in treating lung cancer, including cisplatin
 the mechanism of action of this drug is linked to its aptitude to crosslink with DNA’s
urine bases to form DNA adducts.
 Although cisplatin has a strong anti tumor activity, it has certain adverse and side
effects.
 The adverse effects of this drug include
◦ renal toxicity,
◦ ototoxicity,
◦ myelosuppression,
◦ vomiting, anaphylaxis
◦ Nausea, and
◦ cardiotoxicity
Conclusion

 Aldossary S. A. (2019). Review on Pharmacology of Cisplatin: Clinical Use,
Toxicity and Mechanism of Resistance of Cisplatin. Biomed Pharmacol
Journal. 12(1).
 Dasari, S., & Tchounwou, P. B. (2014). Cisplatin in cancer therapy:
molecular mechanisms of action. European journal of pharmacology, 740,
364–378.
 Lemjabbar-Alaoui, H., Hassan, O. U., Yang, Y. W., & Buchanan, P. (2015).
Lung cancer: Biology and treatment options. Biochimica et biophysica
acta, 1856(2), 189–210.
 Michaels, C. (2016). The importance of exercise in lung cancer. Tranl Lung
Cancer Res. 5(3), 235-238.
 PDR (n.d.). Cisplatin-Drug summary. Retrieved from
https://www.pdr.net/drug-summary/Cisplatin-cisplatin-1472.4558
 Siddiqui F., & Siddiqui A.H.(2019). Cancer, Lung. [Updated 2019 Mar 14]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Retrieved
from https://www.ncbi.nlm.nih.gov/books/NBK482357/
References