ISSN (Print): 1568-0096
ISSN (Online): 1873-5576
Volume 19, 11 Issues, 2019
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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576
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Special Issue Submission
"This journal fills an important need in providing reviews, covering the moving area of new cancer drug targets."
CRC Centre for Cancer Therapeutics, England
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Saeed Samarghandian(Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran)
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36 Articles Ahead of Print are available electronically
As the Guest Editors of this special issue of the Journal “Current Cancer Drug Targets”, we are pleased to present you the
current issue focused on “Current Cancer Drug Development Strategies”
Cancer and non-controllable inflammation (also termed nonresolving inflammation) constitute enormous public health burdens
worldwide and the treatment of these highly complex diseases remains a technological bottleneck. There is an urgent need
to develop new and innovative technologies that could improve the current treatments, and identify new cancer drug targets for
intervention. Because cancer and the nonresolving inflammation diseases are complicated, our treatment strategies should be
accordingly multiplex. This thematic issue of Current Cancer Drug Targets covers medicinal nanotechnology, photodynamic
therapy (PDT), PI3K/Akt pathway inhibition, drug combination for comprehensively controlling key cancer metastatic pathways,
animal models for screening cancer drug target.
The advent of nanomedicine holds great promise to improve the treatment of various diseases, including cancer. In the context
of nanomedicine-based therapeutics, the unique properties of nanoparticles make it easier for targeted drug delivery to cancer
tissues with multi-functionality. Xie et al., discussed the characteristics of cancer including tumor angiogenesis, abnormalities
in tumor blood vessels, uncontrolled cell proliferation markers, multidrug resistance, tumor metastasis, cancer cell metabolism,
and tumor immune system that provide opportunities and challenges for nanomedicine to be directed to specific cancer
cells and portrayed the progress that has been accomplished in the application of nanotechnology for cancer treatment. As cancer
therapy requires close collaboration among clinicians, biological and material scientists, and biomedical engineers with the
joint efforts of researchers in various fields, the information presented in this review can provide useful references for further
studies on developing effective nanomedicine for treatment of cancer.
As a representative of the drug delivery system, mesoporous silica nanoparticles (MSNs) have shown great potential as
good candidates for drug delivery and biomedical application. Pu et al., described the most recent progress in silica-assisted
drug delivery and biomedical applications using different types of Cargo, including (1) anticancer drugs, (2) antibacterial
agents, (3) gene delivery, (4) photodynamic therapeutic agents, (5) bioimaging agents and others. The collected information
about the in vitro and in vivo bioactivity of MSNs and the current status of preclinical trials about drug-loaded MSNs in this
review could provide useful references for the rational design of MSN-based drug delivery systems for clinical use.
Relative to inorganic materials, organic materials such as block copolymers have shown wider applications in drug delivery.
Poly(lactic-co-glycolic acid) (PLGA) was used to entrap curcumin (CUR) for treating ulcerative colitis (UC), a chronic relapsing
disease by Ma et al. They compared the oral efficacy of CUR-loaded microparticles (CUR-MPs) and CUR-loaded nanoparticles
(CUR-NPs) in treating UC, and found that CUR-NPs showed a superior therapeutic efficacy in alleviating colitis in comparison
to CUR-MPs. The research provided the evidence that the particle-based UC therapy exhibited size-dependent behavior.
Cao et al., used paclitaxel-loaded poly(L-phenylalanine)-b-poly(L-aspartic acid) nanoparticles to enhance penetration of
paclitaxel to multidrug resistant cells. The pharmacokinetics and the biodistribution results demonstrated that drug loaded in
nanoparticles could effectively reduce plasma peak concentration and extend plasma circulating time as compared to paclitaxel
injection, and the nanoparticles could markedly, passively target the mononuclear phagocyte system (MPS)-related organs.
Their study provided an effective approach for the development of anti-tumor nanomedicine with drug-resistant reversal effect.
Recently, plant-derived medicinal compounds are becoming an important research area for cancer drug development, especially
as safe and effective agents for cancer metastasis chemoprevention. Zou et al., reviewed the great potential of a naturally
abundant pentacyclic triterpenoid compound ursolic acid (UA) used as a candidate drug in the field of cancer therapy relating to
the suppression of tumor initiation, progression and metastasis. In this review, they introduced the molecular anticancer mechanism
of UA, and highlighted its important role in chemoprevention of tumor metastasis. They also summarized the current development
of novel UA derivatives, pro-drugs, co-drugs as well as nanoformulations, such as liposomes, chitosan, polymers
and mesoporous silica nanoparticles used as a candidate drug for potential application in the field of cancer therapy and cancer
metastasis chemoprevention. The information presented in this review can provide useful references for further studies in making
UA a promising anti-cancer drug, especially as a prophylactic metastatic agent for clinical applications.
Targeted drug/gene delivery systems are widely used in cancer treatment since they can improve tumor targeting, reduce the
side effect of chemotherapy agent as well as enhance the efficacy of gene transfection into target cancer cells. Yan and coauthors
investigated the enhanced anticancer efficacy of one novel nano complex named as “AuNC/PEI/miRNA/HA”, which
could both effectively enhance gene delivery efficiency and regulate gene expression in the context of miRNA interference.
Combining gene and PDT, the novel nano complex could significantly promote apoptosis and improve TIMP-3 mRNA expression
in Bel-7402 cell. They are developing this nanocomplex as an efficient and safe carrier for microRNAs to hepatocellular
carcinoma (HCC) treatment. Jiang et al., introduced a novel nano drug delivery system based on the third-generation
polyamidoamine dendrimer as a nanocarrier for PDT. The optimized system significantly improved the solubility of ZnPcC4
with a higher singlet oxygen production efficiency. Their results provided a facile approach for the design and fabrication of composite nanomaterials with remarkably boosted anticancer effect.
Combination therapy is an effective strategy for comprehensive cancer therapy. Xu et al., investigated a novel quadruple
drug combination consisted of mifepristone, aspirin, lysine and doxycycline (HAMPT) for synergistically controlling key cancer
metastatic pathways. By using this combination therapy, a good adhesion inhibited ratio was exhibited, and cancer cell migration
was inhibited. Moreover, the in vivo experiment indicated that HAMPT could suppress the metastasis of CT-26 cells to
mouse lungs in a dose-dependent manner without marked side effects. Their study demonstrated that HAMPT is a safe, effective
and affordable cancer metastatic chemopreventive agent that can effectively prevent cancer recurrence and metastasis.
Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is known to play important roles in cancer cell growth, invasion, migration
and metastasis. Liu et al., explored the anti-metastatic activities of pan-PI3K inhibitor ZSTK474 in prostate cancer DU145
cells. Their work showed that ZSTK474 potently inhibited DU145 cell migration, invasion and adhesion by negatively regulating
the expression of VEGF, Integrinβ1, MMPs and HIF-1α proteins, which are well-known to be related to angiogenesis and
metastasis. The in vitro and in vivo results demonstrated the potential anti-metastatic effect of ZSTK474 as a novel PI3K
inhibitor in prostate cancer.
Finally, Wang et al., systematically overviewed the pros and cons of animal models to provide information to researchers in
pharmaceutical chemistry and bio-chemistry field for smartly selecting the suitable predictive model for anti-cancer drugs with
the different mechanisms. They also emphasized the pharmaceutical challenges behind and ahead. The information will help us
select the optimal in vitro or in vivo experimental model and to correctly respond to the presence or potential side effects of
drugs for the patients providing a reference to clinical trials.
Current development of targeted therapy and multidisciplinary approach for new treatment modalities, has contributed to
increase the outcome in cancer patients. Based on the new knowledge of molecular features of the tumor, it is urgently needed
to clarify some aspects on new treatments.
Actually the innovative approach in oncology is represented by: a) the development of anticancer targeted drugs; b) growing
member of elderly cancer patients; c) constant augmentation of so-called “cancer survivors”; d) infection-related neoplasms
(HIV, HPV, EBV, HHV8 and Hepatitis Virus); and lastly, e) the colossal healthcare cost to support all these new treatments.
In order to comprehend well these “new” issues for the upcoming future, it is necessary to make some reflections . The
end of the 2nd Millennium has been characterized by the introduction of new molecules in cancer treatment allowing “target
therapy”. Targeted drugs are principally small inhibitor molecules (i.e. erlotinib, imatinib etc.) and monoclonal antibody (i.e.
trastuzumab, rituximab, ipilimumab, nivolumab, etc.) that interfere directly in the molecular mechanism of proliferating
pathways, reducing traditional toxicities of antiblastic chemotherapy (AC).
The mechanism of action of these new targeted molecules is universal in all neoplastic cells carrying the corresponding
cancer target, but some of these have been approved by drug labeling studies. Efficacy failure is recorded when the therapeutic
indication has been extended to other types of cancer (e.g., erlotinib in metastatic pancreatic cancer). However, an appropriate
study on resistance, efficacy of long-term treatment and outcome is mandatory for tailored cancer therapies. Furthermore, new
drugs indication must only be approved by an appropriat clinical trial. Currently these issues exist for drugs with strong
evidence to improve personalized label or schedule (i.e., cetuximab used only in KRAS mutational status, duration of adjuvant
trastuzumab); or an existing anticancer agent for another therapeutic indication (i.e., imatinib in sclerodermatous). Often,
pharmaceutical corporations do not support these studies due to rarity of the disease. These problems occur recurrently in the
context of a low subset of targeted population (i.e., cancer with mutations frequency lower than 2%) .
Targeted therapy has introduced new economic reflections: for example substituting traditional chemotherapy (often needs
vascular access and intravenous infusions) to oral small molecule inhibitors, eliminates some costs by moving therapy from the
hospital to home . On the other hand, if therapy includes monoclonal antibodies (mAbs), the costs dramatically increase
(Table 1) calculated that the cost of $30,790 of the eight weeks treatment regimens containing bevacizumab or cetuximab in
colorectal cancer was calculated, compared with $63 for the same period of 5-fluorouracil, leucovorin and oxaliplatin regimen
Current treatments of cancer are derived through validated clinical trials, that include, often, innovative patented drugs.
Nevertheless, global contemporary model of community healthcare systems highlights that new therapeutic care must be
carried out at an equal or lower cost. Besides, trials evaluating the precise economic impact of cancer treatments are still few.
Advanced methods to assess cost-effectiveness, cost-utility and cost-benefit in the cancer organizations have been introduced.
Such as the National Institute for Health and Clinical Excellence (NICE). NICE has established several clinical Advisory
committees, which stimulate Academic and Pharma societies to design studies, including economic models for personalized
healthcare . Personalized medicine is a promising model which includes genomic tests due to specific tailored treatments .
It is well known that Pharmacogenomics tests, performed before drug treatment, minimize toxicity and maximize benefits and
provide higher quality of life . NICE also provides a method to measure Quality-Adjusted Life-Years (QALY), combining
data on outcomes, analytical assay and cost-effectiveness for entire treatment.
The up-coming methods to measure the QALYs will lead to multidisciplinary treatment approach for decreasing the costs of
Progress in cancer treatment is driven by cumulative knowledge of the molecular cancer pathways, and the subsequent
development of systemic agents that inhibit critical neoplastic pathways. However, not all new molecules with biological target
are automatically approved. The base for their US Food and Drug Administration (FDA) approvals differ: an upgrading in
overall survival (OS) compared with a current therapy is not always required;  toxicity profiles and progression-free survival
are also considered as important factors .
Finally, we contemplate that the recent progresses have provided exceptional opportunities to identify prognostic and
predictive markers of efficacy of antiblastic treatments . Genetic markers can be used to identify patients who will benefit
from therapy, excluding patients at high risk to develop severe adverse events, and adjust dosing .
Furthermore, trials evaluating the pharmacoeconomic impact of genotyping assay on cancer therapy are still few. Also, the
major issue to consider for genotyping is the need to interpret laboratory data results by an oncologist . However,
inadequate education of the physicians regarding Pharmacogenomics field has been observed . The contemporary
knowledge of healthcare professionals concerning pharmacogenomics is still limited, and teaching programs are poor in this
field. However, new method to measure cost-effectiveness in cancer therapy have already been proposed .
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