Cure For Cancer - Assignment

could you please see the attachment carfully and do the two part A ( about 300 words ) and B about 1200 words

Running head: CURE FOR CANCER
Cure For Cancer
Name of the Student
Name of the University
Author Note

1CURE FOR CANCER
According to this, nurse
leaders at all levels must
a) The selective toxicity of anticancer drugs
The selective toxicity of drugs for cancer refers to the toxicity of the anticancer drugs
towards diseased or cancer cells and non-toxic towards the healthy cells. Those drugs that
have specific targets are efficient in killing the cancer cells but some cancer cells develop
resistance for the same drug to which once it was susceptible because of genetic changes
where anticancer drugs possesses toxicity towards healthy cells (Liu et al. 2015). There are
several drug toxicity mechanisms such as toxicity specific to the target and knowing the
mechanism of action will help the cancer patients to avoid side effects of the drugs such as
alkylating agents can damage cells by inhibiting DNA synthesis but alongside damage the
bone marrow leading to white blood cell cancer (leukemia) when the dose of these alkylating
agents are higher and the patient develops a risk of developing leukemia after 10 years of
treatment (Poganitsch-Korhonenet al. 2017). Antibiotics such as anthracyclines act as
antitumor drugs by interfering with DNA replication but can cause heart damage when given
at high doses (McGowan et al. 2017). Before allocating the drugs for cancer therapy it must
go through clinical trials to understand its potential. Drugs are evaluated for its antitumor
activity at low concentrations in animal models but do not assure its activity in humans,
therefore, drugs with efficacy to improve the survival rate of treatment in animal models may
show anticancer activity in humans. Patients require drugs that kill cancer cells at low
concentrations and leave the healthy cells unaffected (López-Lázaro, 2015). Therefore it is
important to understand that a drug that is effective in cancer treatment of rodents will have
the ability to kill cancer cells selectively (Calderon-Montano, Burgos-Moronand and Lopez-

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Lazaro 2014). To avoid non-specificity of drugs leading to a reduction in survival rate they
must be targeted toward specific sites infected with cancerous cells.
b) Limitations of chemotherapy and ways to reduce them
Chemotherapy is advantageous over other therapies for cancer treatment because it
can spread throughout the body killing extensive cancers but it comes with limitations
including side effects, resistance to the chemotherapeutic drugs and require a combination of
therapies (Liu, H., Lv, L. and Yang, K., 2015). A study shows that cellular senescence ceases
proliferation of cancer cells whereas these dead cells are associated with a pro-inflammatory
secretory phenotype thereby exhibiting adverse side effects (Demaria et al. 2017). Side
effects of these drugs limited chemotherapy and the symptoms included weakness and fatigue
ranking highest followed by headache, vomiting, hair loss, diarrhea, abdominal cramps,
memory loss in patients provided chemotherapy for breast and cervical cancer. Side effects
vary among different cancer types (Aslam et al. 2014).
Cancer cells gain resistance through a variety of mechanisms - firstly through the
reduction in the drug build-up of drugs and its increased export, altered target sites fro drug
and molecules for signal transduction, increased repair mechanism of DNA after being
induced by the drug and finally escaping apoptosis (Ramos and Bentires-Alj, 2015).

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Figure 1: Several mechanisms of resistance to chemotherapy. This figure shows
decreased activation of prodrugs intracellularly or its increased inactivation, alterations in the
molecular structures of the transporters for the drugs, abnormal cell death and autophagy can
develop resistance to anticancer drugs.
(Image retrieved from Ramos and Bentires-Alj, 2015)
The transporters of anticancer drugs belong to the ABC transporters that is ATP-
binding cassette that facilitate the transport of biomolecules along with drugs in one direction
and ATP hydrolysis provides the energy to transport these molecules against the
concentration gradient. This forms a defense mechanism for selective entry into both normal
and abnormal cells but overexpression of these transporters can develop resistance to various
cytotoxic agents specifically for chemotherapy, for instance, a transporter called P-
glycoprotein when overexpressed in cancer cells causes resistance to chemotherapeutics such
as anthracyclins and actinomycin D by effluxing the drug out of the cells leading to
chemoresistance (Nanayakkara et al., 2018).

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Figure 2: Mechanism of drug resistance including apoptotic evasion by inducing resistance to
inducers of apoptosis.
( Image retrieved from Hu et al., 2016)
Figure 2 shows how apoptosis is evaded. Anticancer drugs upon DNA damage
activate p53 that induce apoptosis by increasing the expression of Bax and suppression of
anti-apoptotic protein Bcl-2 but in tumor cells, there is overexpression of these anti-apoptotic
proteins whereas the apoptotic proteins p53 are suppressed due to mutation. Therefore
alteration of the expression of these proteins leads to the low sensitivity of DNA damage by
anticancer drugs and resistance to apoptosis (Hu et al., 2016).

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Tumor resistance can also occur due to abnormal autophagy. Many studies are
conducted to inhibit autophagy with the help of combination therapies but it was seen that
drug treatment increased cancer cell growth therefore inhibition of abnormal autophagy by
anti-tumor drugs is under clinical trial. There are various contradicting studies being
performed on stimulation or inhibition of autophagy as an anti-tumor effect therefore the
correct intervention for inhibiting autophagy is not yet confirmed. For instance drugs like
erlotinib require autophagy to be induced in order to inhibit EGFR mutation in lung cancer
(Thorburn, Thamm and Gustafson 2014).
Figure 3: EGFR inhibition by anticancer drugs and induced autophagy through the
stimulation of a number of signaling molecules.
( Image retrieved from Kwon et al. 2019)
To reduce resistance to chemotherapy drugs, a combination of therapies can be used
such as a combination of radiotherapy, cancer surgery and chemotherapy. Radiation therapy

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and surgery are localized remove or kill cancer cells whereas chemotherapeutic drugs are
given for cancer that has spread throughout the body. Neoadjuvant therapy is where the
radiation and drugs are given to reduce the size of the tumor before surgery but to improve
the chances of recurrence of cancer, adjuvant therapy that is radiation and drugs are given
after the surgery to destroy residual cancer cells. Combination therapy depends on the type
and stage of cancer such as ea cancer be treated with surgery at early-stage or given
combination therapy at the later or last stage such as locally advanced breast cancer. But
combination therapy only reduces the symptoms of cancer where surgery or radiation will not
work such as in the case of lung cancer and esophageal cancer (McElnay and Lim 2014).
To increase the antitumor effectivity of drugs, molecular targeted therapies have
evolved using drugs that use various molecular pathways such as cell growth and cycle,
invasion, and angiogenesis which are hallmarks of cancer as molecular targets for treating
cancer. This targeting method is useful in various types of tumors such as colorectal cancer,
breast cancer, gastric and skin cell cancer. These drugs include inhibitors of angiogenesis,
Epidermal growth factor receptor(EGFR) and cell cycle.
Figure 4: Drugs used for molecular targeting of gastric cancer
(Image retrieved from Song et al. 2017)

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Figure 4 shows various targeted sites such as EGFR, VEGFR, PD-L1, and c-MET.
EGFR is a transmembrane growth factor receptor protein of the family of tyrosine kinase that
is specific for its ligand EGF (epidermal growth factor). The ligand-receptor binding causes
the activation of a number of signaling molecules inside the cell through phosphorylation of
tyrosine kinase following which tumor cell division is promoted along with new vessel
formation and migration. These receptors can act as target sites for therapeutic drugs such as
cetuximab, 5-fluorouracil, leucovorin and irinotecan which comprises monoclonal antibodies
against EGFR and tyrosine kinase. These drugs inhibit cell growth and proliferation in tumors
and reduce the rate of tumor formation to about 44% in patients with gastric cancer. Other
inhibitors are shown in the figure work in a similar way of inhibiting target sites of cancer
cells (Song et al. 2017).
A very advance way of overcoming side effects of chemotherapeutics can be
manipulating stem cells to behave like therapeutic agents against tumor cells (Stuckey and
Shah 2014). Figure 5a) shows the way by which stem cells generate proteins that function on
tumor cell or microenvironment surrounding the tumor. Proteins such as epidermal growth
factor, interferons or ligand inducing tumor necrosis factor or apoptosis are secreted induce
respective receptors. Stem cells can also be manipulated to secrete effectors of blood vessels,
immune system or stroma. In figure 5b) stem cells are manipulated to express suicide genes
that encode enzymes to convert prodrug into a functional drug that is a cytotoxin which
shows the effect on both the stem cell and the cancer cells. Figure 5c) shows how
nanoparticles can be used as carriers for stem cells for releasing it in the surrounding area of
the tumor either passively or as a response to external stimulus. Figure 5d) shows that stem

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cells can be artificially infected with viruses capable of oncolysis that infect the cancerous
cells and spread the infection throughout the tumor.
Figure 5: Using stem cells to promote tumor cell death
(Image retrieved from Stuckey and Shah 2014)
Therefore a cancer patient should be given an appropriate dosage and duration of
chemotherapy to have minimal side effects and maximal efficacy. Using combination therapy
or any alternative therapy such as stated above can be useful in eliminating antitumor drug
effects on healthy cells.

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References
Aslam, M.S., Naveed, S., Ahmed, A., Abbas, Z., Gull, I. and Athar, M.A., 2014. Side effects
of chemotherapy in cancer patients and evaluation of patients opinion about starvation based
differential chemotherapy. Journal of Cancer Therapy, 2014.
Calderon-Montano, J.M., Burgos-Moron, E. and Lopez-Lazaro, M., 2014. The in vivo
antitumor activity of cardiac glycosides in mice xenografted with human cancer cells is
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Demaria, M., O'Leary, M.N., Chang, J., Shao, L., Liu, S.U., Alimirah, F., Koenig, K., Le, C.,
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