International Journal of Pharmaceutical Chemistry and Analysis 2023;10(4):229–236

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International Journal of Pharmaceutical Chemistry and

Analysis
Journal homepage: https://www.ijpca.org/

Review Article
Recent advances in anticancer drug discovery: A review

Kuleni Nemomsa1 , Alemu Tadesse 1 *, Frehiwot Beyene1

1 Dept. of Pharmaceutical Chemistry and Pharmacognosy, Addis Ababa University School of Pharmacy, Ababa, Ethiopia

ARTICLE INFO ABSTRACT

Article history: Cancer is a process of uncontrolled cell proliferation that leads to the development of an abnormally
Received 30-09-2023 growing tumor, determining initially a local disease that might spread, impairing other organs or important
Accepted 30-10-2023 processes. One of the most fatal diseases in recent times, cancer kills many lives each year. The effective
Available online 21-12-2023 management of this condition has been impacted by the variances in the disease across the globe, the impact
of the medical facilities that are available, and other socioeconomic issues. The aim of this study was to
summaries previously published articles regarding recent advances in anticancer drug discoveries. In this
Keywords: review, previously published literature regarding recent advances in anticancer drug discovery collected
Cancer from journals through PubMed Central, Google Scholar, and Science Direct from March 20 to May 12 was
Drug discovery
identified well, and points that I assumed were important and recent (2017–2023) were included. Based
Drug targets
on my searches, numerous discoveries are identified and grouped as anticancer drug targets, plant derived
Drug repurposing advances, chemical compounds with in vivo or in vitro cytotoxic drug discovery, and repurposing advances.
Cytotoxic drug 1 Based on a variety of articles published by scholars, this review summarizes some recent advancements in
anticancer drug discovery. Under this broad topic, promising and clinically evidenced drug targets for
anticancer drug binding, some drugs repurposed for cancer treatment, plant-derived advances in cancer
therapy, and finally advances in novel chemical compounds in the area of cancer therapy are reviewed.

This is an Open Access (OA) journal, and articles are distributed under the terms of the Creative Commons
Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon
the work non-commercially, as long as appropriate credit is given and the new creations are licensed under
the identical terms.
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1. Introduction been impacted by the variations in the disease across

the globe, the impact of the medical facilities that are
Cancer is a condition where cells grow uncontrollably,
available, and other socioeconomic factors. 4 According
forming tumors that develop abnormally and can spread
to the 2023 global cancer statistics, there will be 20
to other organs or vital systems, impairing their ability to
million additional cases of cancer and 10 million deaths
function. 1 Several determinant agents, including genetic
from cancer. Over the following two decades, there
mutations, pollution, food contaminants, viruses, chemicals,
will be a roughly 60% increase in the cancer burden,
and ionizing radiation, interact to cause cancer, which
placing additional strain on communities, individuals,
is why it is regarded as a multifactorial disease. 2
and health systems.
Multiple evolutionarily conserved cell cycle control
According to research done in Ethiopia between
mechanisms tightly regulate cell division to guarantee the
2000 and 2016, cancer was responsible for an estimated
generation of two genetically identical cells. 3 One of the
50,913.5 (95%) deaths among people of all ages and
deadliest illnesses in recent memory, cancer claims many
both genders (the majority of the patients were females),
lives each year. The proper management of this disease has
with a crude death rate of 49.7 per 100,000 and an age-
* Corresponding author. standardized death rate of 93.5 per 100,000. The number
E-mail address: [email protected] (A. Tadesse). of cancer cases has increased to previously unheard-

https://doi.org/10.18231/j.ijpca.2023.039
2394-2789/© 2023 Author(s), Published by Innovative Publication. 229
230 Nemomsa, Tadesse and Beyene / International Journal of Pharmaceutical Chemistry and Analysis 2023;10(4):229–236

of levels as a result of longer life expectancies. As a related to recent advances in anticancer drug discovery.
result, the pharmaceutical sector has invested a sizable These findings are grouped into three major categories:
amount of money in this therapeutic field. Despite anticancer drug targets and biomarkers; in vitro and in vivo
these efforts, the field of cancer drug trials on newly cytotoxic drug advances; and plant-derived
research continues to be remarkably difficult, and advances. Additionally, advances in drug repurposing are
therapeutic advancements have not included. Furthermore, studies on drug repurposing are
yet produced the anticipated clinical outcomes. 5 However, added, including those involving approved, discontinued,
since the first half of the 20t h century, drug manufacturers and shelved medications with anticancer activity.
have continued to produce medicines despite their high Additionally, studies on electrochemotherapy, gene
cost-benefit ratio by taking into account the improved therapy, phytomedicine, and immunotherapy are included.
understanding of the disease’s physiopathology. 6,7 Drug
companies have created a variety of anticancer drug classes,
such as cytotoxic drugs (alkylating agents, antimetabolites, 3. General Overview of Anticancer Drug Discovery
antibiotics, plant extracts, and other cytotoxic
drugs), hormones and hormone antagonists, and
immunomodulators. 8,9 Due to their intricate, pricey, time-consuming, and
However, these chemotherapies have issues difficult tasks, researchers and drug manufacturers
with lack of specificity, cytotoxicity, induction of have faced significant challenges in the design and
multi-drug resistance, and stem-like cell growth. 10 discovery of anticancer drugs. 11 Aside from the
The identification of new molecular targets has raised complexity, first-hand treatments are extremely toxic
hopes for creating better treatments. The main and do not target cancer cells specifically. 12,13 This
obstacles in cancer drug discovery, improving drug is true even though manufacturers are working on
selectivity and lowering side effects, have been developing anticancer drugs. It is therefore of great interest
addressed by monoclonal antibodies and antibody- to design and develop novel, selective small-molecule
small molecule conjugates. 5,10 Manufacturers and drugs, especially with the aid of in silico tools that have
researchers have published a ton of literature on been developed in recent years. 14 But recently, artificial
drug targets and new drug development strategies by intelligence (AI) has emerged as a strong and promising
taking into account the difficulties of anticancer drugs, technology for quicker, less expensive, and more efficient
their toxicity profiles, non-selectivity characteristics, anti-cancer drug designs than the previously employed
and related side effects. This review therefore CADD. 11 The search for novel drug molecules and the
aims to compile and summarize a collection of synthesis of more appealing drug molecules can both be
publications centered on novel chemical compounds sped up by artificial intelligence. Target identification
with cytotoxic activity on cancer cells in vitro, or both, in is the first step in the anti-cancer drug discovery process,
particular novel biomarkers and target proteins with and after that comes structure-based, ligand-based, and
potential therapeutic properties. fragment-based screening of successful compounds,
de novo anti-cancer drug design for large compounds,
1.1. Searching strategy anti-cancer drug repurposing, and precise anti-cancer
drug reaction prediction. 15,16
From March 20 to May 12, previous study data on the
discovery of anticancer drugs was gathered from journals Anticancer medications advance as they are discovered
using PubMed Central, Google Scholar, and Science Direct. from natural products or synthetically, taking into
To make it simple for referencing, literature was accurately account the toxicity and efficacy of medications and
retrieved, sorted out based on the topic’s proximity and using this artificial intelligence-based advanced technology
the publication date, and then directly cited from the or previous CADD as a tool for drug design and discovery.
publications. As of late, drug repurposing based on promising
targets has also become popular. 17–19 However, there
2. Materials and Methods are drawbacks to cancer immunotherapy, such
In this review, the reviewer uses websites such as Google as resistance, the ability of cancer cells to evade the
Scholar, PubMed Central, and Science Direct as searching immune response, and issues with delivery methods. 20
tools via a personal computer and other accessories. Nanoparticles using nanocarriers as vehicles have some
issues that could solve these issues, according to recent
advancements. 21 Because of their special qualities,
2.1. Searching results
such as biocompatibility, decreased toxicity, increased
After searching and filtering recently published literature permeability, improved stability, precision targeting, and
via the above strategies, I found that many of the articles retention effect, 22 nanoparticles can be used to treat cancer.
 Nemomsa, Tadesse and Beyene / International Journal of Pharmaceutical Chemistry and Analysis 2023;10(4):229–236 231

4. Recent Advances in Anticancer Drug Targets and and develop safer and more effective drug candidates, a
Biomarkers number of tubulin-targeting agents have been synthesized,
and structure-activity relationship studies have been carried
Targeted therapy holds the key to raising overall out. 24,26
survival rates while lowering the unfavorable side effects
of cancer treatment. Compared to patients who did
not receive matched targeted therapies, patients
who did both overall survival and progression-free
survival significantly improved. 23 For the purpose of
treating cancer, numerous drug targets have been found.
Due to efficacy or toxicity issues, the majority of
molecularly targeted agents were ineffective. Researchers
are being challenged to concentrate on the drug targets
that can aid in the complete eradication of the disease by
recent work in the field of molecular biology and a better
understanding of the molecular pathology of cancer. 24
4.3. Vascular targeting agents
4.1. Kinases as targets
Vascular targeting agents (VTAs) are primarily cancer
A group of anti-cancer medications known as kinase therapies that are created specifically to target the
inhibitors directly interact with the active site of the tumor’s vasculature and, as a result, prevent the growth
target enzyme to prevent kinase activity. According and development of tumors. Given the availability of blood-
to estimates, the human genome contains about 2000 borne medications, it becomes a successful strategy in
kinases that are either serine/threonine- or tyrosine- the treatment of cancer. A steady flow of oxygen and
specific and connected to one another. 24 Clinical nutrients is necessary because tumor cells divide rapidly.
oncology was first introduced to imatinib, then Therefore, the growth of blood vessel networks is necessary
to bosutinib, sorafenib, and sunitinib. Despite having the for the development, progression, and metastasis of
same mode of action—competitive ATP inhibition at tumors. Vascular disrupting agents (VDAs) can stop blood
the tyrosine kinase catalytic binding site—they are distinct flow to tumors. 27,28
from one another in terms of the range of targeted kinases,
their pharmacokinetics, and the negative effects that
are substance-specific. 25

4.2. Tubulin/ microtubule as target

A major component of the eukaryotic cytoskeleton,
microtubules are formed by the polymerization of
the globular protein tubulin, which has a molecular
weight of 52 KD. Through each stage of the cell cycle,
microtubules continuously lengthen and shorten.
4.4. Angiogenesis inhibitors
Compared to normal cells, cancer cells rapidly divide
and expand. The development of microtubule-targeting A brand-new class of medicines called angiogenesis
agents for the treatment of cancer is being investigated inhibitors is intended to prevent tumor vascularization.
because they are essential for cell division and growth. VEGF-A is overexpressed in tumor growth, invasion, and
As a result, the development of anti-cancer medications metastases. Targeting VEGF-A at the moment are VEGF-
now includes tubulin as one of their key targets. To find A and VEGFR2 inhibitors 28 . Non-small-cell lung cancer
232 Nemomsa, Tadesse and Beyene / International Journal of Pharmaceutical Chemistry and Analysis 2023;10(4):229–236

(NSCLC) is treated with angiogenesis inhibitors, such as selective COX-2 inhibitor celecoxib inhibited the growth
bevacizumab and ramucirumab. These medicines aim to of breast cancer cells and decreased tumor development. It
block VEGFs. 29 was discovered that the level of COX-2 expression and
the invasiveness of the tumor cells were required for
growth inhibition. 35 Mesalazine has also been mentioned
as having anti-cancer potential in a variety of cancers,
including colorectal cancer, gastric cancer, breast cancer,
and colon cancer. 36

4.5. Monoclonal antibodies

To stop tumor vascularization, a new class of drugs called
angiogenesis inhibitors is being developed. Tumor growth,
invasion, and metastases all exhibit overexpressed
VEGF-A. VEGF-A and VEGFR2 inhibitors currently
target VEGF-A. 28 Angiogenesis inhibitors (AIs), like
bevacizumab and ramucirumab, are used to treat
non-small-cell lung cancer (NSCLC). These drugs
5.3. Antidiabetic agents
try to stop VEGFs. 29
The first line of treatment for type 2 diabetes mellitus
5. Recent Advances in Drug Repurposing for the is metformin, an oral medication. Numerous cancer
Discovery of New Anticancer Drugs types, including pancreatic, endometrial, breast, lung,
and prostrate, have shown it to have anti-neoplastic
Drug repositioning, another name for drug repurposing, is activity. 37 Through numerous preclinical and clinical
a tactic that looks at additional diseases besides the one for studies, thiazolidinediones (TZDs) have been identified as
which a drug has already received approval. 30–32 a potent lead in the treatment of breast and prostate cancer.
Troglitazone, rosiglitazone, and pioglitazone are the three
5.1. Antiplatelet Agents key components of this medication. 38
Although aspirin’s clinical use as an anticancer medication
has been expanded and regular use of the
medication is associated with a lower risk of breast cancer,
aspirin is primarily used as an antiplatelet medication for
cardiovascular diseases. Henry et al. suggests that aspirin
and PI3K inhibitors may be used in combination therapy to
treat breast cancer. 33

5.2. Anti-inflammatory drugs

According to recent in vivo data, diclofenac
successfully slows the growth of pancreatic tumors
in mice. Diclofenac therapy resulted in a rise in
apoptosis and a fall in angiogenesis, according to
analysis of the tumor tissue removed during surgery.
5.4. Anthelmintic agents
Additionally, melanoma cells were used to test the
effectiveness of a diclofenac and sorafenib (a kinase Treatment with repurposing pleiotropic benzimidazole
inhibitor) combination, and the results were positive for all anthelminthics like flubendazole and albendazole has
cancer cells. 34 Furthermore, in in vivo rat models, the recently opened a new window due to their simple
 Nemomsa, Tadesse and Beyene / International Journal of Pharmaceutical Chemistry and Analysis 2023;10(4):229–236 233

accessibility, affordable price as a generic drug, and

long history of safe use in the human population.
These pleiotropic benzimidazoles are potent microtubule
disruptors, anti-angiogenic, anti-metastatic, immune
checkpoint, hypoxia-inducible factor, epithelial-
mesenchymal transition, cancer stemness, and multidrug
resistance protein 1 inhibitors, as well as inducers of
apoptosis and M1 polarization, according to extensive
preclinical research and a small number of clinical trials. 30

5.6. Antiviral drugs

Zidovudine, a reverse transcriptase inhibitor, was
the first drug approved to treat HIV infection.
It also exhibits anti-cancer properties against a
number of cancer types, including pancreatic,
leukemia, and Kaposi sarcoma. Similar to
this, Brivudine, a medication used to treat herpes
simplex virus, demonstrated anti-cancer properties
by reducing chemoresistance.[88] In ovarian, pancreatic,
and breast cancer cells, ritonavir has been shown
5.5. Antipsychotic agents to reduce cancer cell growth and division and to speed
up apoptosis. 46,47

Several studies have shown that individuals taking

antipsychotic medications for psychiatric conditions
like schizophrenia have decreased incidences of
colon, rectal, and prostate cancer, 39 indicating that
antipsychotic medications do have anti-cancer potential.
In colon, glioma, and gastric cancer, the drug aripiprazole,
which is prescribed to patients with schizophrenia, slows
down cell division and tumor growth. 40,41 Sertindole
is a promising candidate drug for the treatment of Figure 1:
gastric and breast cancers. 42 Valproic acid, a common
neuroleptic drug used to treat epilepsy, bipolar disorder, and
migraines, has been found to use epigenetic mechanisms,
5.7. Antifungal agents
such as the inhibition of histone deacetylases, which further
reduce tumor cell proliferation, cause cell differentiation, The antifungal drug itraconazole is known to inhibit the
and inhibit angiogenesis, ultimately leading to cell AKT/mTOR signaling pathway in human umbilical
death. 43 It has been reported that phenothiazines vein endothelial cells (HUVECs), endometrial
inhibit DNA polymerase in mitochondria, induce carcinoma (EC), melanoma cells, and glioblastoma.
differentiation of tumor stem cells, and decrease tumor cell It regulates the signal transduction pathways of
proliferation. Olanzapine, a medication used to treat bipolar Hedgehog, reverses chemoresistance brought on
disorder, schizophrenia, and Tourette syndrome, destroys by P-glycoprotein, and prevents angiogenesis and
tumor cells by upsetting the homeostasis of cholesterol. 44 lymphangiogenesis in cancer cells. 48 Additionally,
There is evidence that selective serotonin reuptake ketoconazole demonstrated anti-cancer activity against
inhibitors (SSRI) reduce proliferation, leading to the death hepatocellular carcinoma, prostate, melanoma, and breast
of tumor cells. 45 cancer. It effectively blocks the biogenesis of exosomes
234 Nemomsa, Tadesse and Beyene / International Journal of Pharmaceutical Chemistry and Analysis 2023;10(4):229–236

in prostate cancer cells while generally being more the many heterometallic-based promising compounds for
tolerable and having fewer negative side effects. 49 cancer treatment. 55,56

With IC50 values ranging from 7 to 19 M against

a panel of human cancer cell lines, the synthesis and
characterization of a number of novel heterocyclic
compounds, including thiazolidin-4-ones, 1,3,4-
thiadiazoles, and thiazoles bearing thymol under mild
conditions, exhibit significant anticancer activity. 57 Due
5.8. Antibacterial agents to its presence in many natural substances, pyrazole, a
five-membered ring with two adjacent nitrogen atoms in
Doxorubicin has been found to be effective in treating
its structure, has been postulated as a potent candidate in
breast cancer. By intercalating breaks into the DNA,
the pharmacological context with an interesting therapeutic
it prevented DNA replication. When combined with
target covering a broad spectrum of biological activities. 58
a COX-2 inhibitor, doxycycline prevents the growth
In vitro tests recently revealed progress in the use of bis-
of colon cancer cells by causing G0/G1 arrest
heterocyclic compounds as efficient anticancer treatments,
and blocking matrix metalloproteinase. Doxycycline
which goes beyond the concern regarding the anticancer
inhibits both the mitochondrial biogenesis process and the
treatment potential of heterocyclic compounds. 59
stem cell phenotype of cancer cells in the context of breast
cancer. 50,51

5.9. Heterometallic compounds

Though platinum-based drugs
are frequently used in medical treatments, their
effectiveness is constrained by their toxicity due
6. Conclusion
to interactions between platinum and biomolecules
that have sulfur as a donor atom, such as thiols and The global impact of cancer is extremely negative.
thioethers. 52 As a result, newly developed mechanisms Beginning with the first nitrogen mustards, researchers and
are creating novel heterometallic complexes with metal pharmaceutical companies tried their best to find
centers that have different coordination geometry, kinetic cures. The lack of selectivity, effectiveness, side
properties, affinity, and reactivity towards biologically effects, and metastatic nature of the diseases
relevant nucleophiles in order to overcome the toxicity of make effective treatment challenging, despite the
platinum-based drugs. 53 Drugs based on heterometallic availability of a wide range of treatment options
materials have a promising future for efficacy above those as alternatives. Recent advances in the field of
based on platinum, in addition to minimizing toxicity. 54 molecular biology and a deeper comprehension of
Platinum, gold, and titanium are more prevalent among the molecular pathology of cancer have pushed researchers
 Nemomsa, Tadesse and Beyene / International Journal of Pharmaceutical Chemistry and Analysis 2023;10(4):229–236 235

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