INTRODUCTION:

Globally, cancer is the leading cause of death due to aberrant tissue growth and unpredictable, uncontrollably divided cells. Environmental variables, genetic mutations, protracted illnesses, or other anomalies could have contributed to the mortality. The word "cancer" refers to a broad category of hereditary disorders that can impact any area of the body.

Other words for cancer include neoplasms and malignant tumors. The fast formation of aberrant cells that spread beyond limits is a pertinent and important characteristic of cancer. One of the main causes of sickness and death in the globe is cancer. 5.8 million Deaths worldwide in 2015 were attributable to cancer. (WHO, 2017)^1-4. Over 70% of Earth's surface is comprised of oceans, which are home to over 200,000 species of invertebrates, algae, and other animals and plants. The marine environment's vegetation and animals are important sources of novel molecular entities. Many new chemicals with biological activity have been identified from marine species over the past few decades. Numerous substances possessing cytotoxic and anticancer properties have been identified from diverse marine origins, including sponges, gorgonian coral, sea algae, sea hares, and cucumbers⁵. Effective therapeutic efficacy is caused by chemically active metabolites, which are abundantly provided by nature. The text reveals that a large number of medicinal anticancer agents come from marine sources and have a variety of application⁶. Marine bacteria are frequently hard to discover in the deep ocean, despite the fact that marine drugs are secondary metabolites can be utilized to treat a variety of infectious disorders. Molecular biology in the 1970s, and at the conclusion of the 1990s, it had advanced globally. Gene production was initiated by David Newman, the Director of the Natural Product Division at the US National Cancer Institute located in Bethesda, Maryland. They got to work on the capacity to cultivate microorganisms. The entire synthesis and structural analysis of genes was taken up by synthetic chemists. Marine Drug Discovery continues to draw newcomers despite the dearth of novel medications available on the market⁷. A wealth of medicinal substances that have exceptional variety and distinct chemical biodiversity have been developed by the marine environment. In 2020, cancer will be the second greatest cause of death, accounting for 10 million deaths. Scientists have worked very hard over the past few decades to understand the pathophysiology of cancer, and they have produced certain marine medications to treat the disease⁸. To protect themselves, marine plants and bacteria need a special chemical repertoire, and scientists studying red communication are eager to learn more about these novel substances⁹. The cancer group comprises over a hundred diseases that can arise practically wherever within the body. Unregulated cell proliferation combined with cancerous traits including metastasis and inversion. These chemotherapy medications have been used in the treatment of cancer for the past 30 to 40 years. These medications have the potential to alter how cells behave at various phases, which ultimately results in death¹⁰. Currently, almost 60% of medicines licensed with the purpose of treating cancer come from the marine industry. These medications have the ability to tackle cancer in multiple stages, thereby avoiding or postponing its development. Marine microorganisms, plants, and mammals have antimutagenic and anticarcinogenic properties¹¹. 2019 marks the 50^th anniversary of the development of Cytarabine, the first anticancer medication derived from marine sources. The medical and scientific community honored the 50^th anniversary of Notable advancements have been made in immunotherapy and biology, as well as in the design and production of contemporary drugs. We can now achieve our goal of curing cancer thanks to this finding. Many cancers have already been successfully treated, and survival rates have been increased. Such as pediatric lymphoblastic leukemia, testicular cancer, and lymphomas. The biodiversity of the marine regions is abundant. A variety of major sources are available for the separation of drugs exhibiting the pharmacological action listed in Table 1.

Marine pharmacology:

The study of compounds with active pharmacological characteristics found in marine plant and animal species is the focus of marine pharmacology, a relatively recent field of pharmacological studies. Marine natural products are typically secondary metabolites that aren't essential to a species' growth, development, or reproduction. The superiority of natural products derived from the sea over those from the land in terms of chemical individuality has previously been established by a comparative research.

LITERATURE REVIEW:

Natural products have always been primarily sourced from terrestrial animals and plants, from human Millennium, Cytarabine (also known as ara-C cytosar-U®). The primary source of this medication is marine sponge. It inhibits the activity of DNA polymerase and has strong anticarcinogenic properties¹². Conventional allopathic medicine states that there are more than 150 different forms of cancer, which can be divided into five primary categories.

One of the most common diseases is cancer, for which the medical establishment struggles to develop effective, location-specific anti-cancer medications. Thus far in these cancer investigations, the majority of synthetic medications had unfavorable side effects. In addition, powerful and safer anti-cancer medications are produced from marine sources as opposed to synthetic ones^13-20.

Nowadays, everyone is paying more attention to identifying Extracts from natural sources and learning about their possible therapeutic uses. As a result, medications derived from nature that are pharmacologically strong and have minimal to no side effects are used in the food industry and in preventative medicine. They are a possible source of novel chemicals with various pharmacological properties. Traditional herbal remedies have a significant role in India's healthcare system^21-27.

Fig. 1: Forms of cancer

Begins to remove the active components from terrestrial plants and animals in order to treat illnesses. As drug development advances, an increasing amount of work is being put into creating novel molecular structures for medications derived from plants and terrestrial animals that can address the growing threat to human health and life. As a result, discovering new drug sources now requires "asking for drugs from sea"²⁸. Marine Natural Product Exploration has turned down a sizable number of medicine candidates in recent years. The majority of these compounds are still in the preclinical or early stages of clinical stages²⁹. The anticancer, antibacterial, antifungal, anti-inflammatory, analgesic, neuroprotective properties of marine natural materials are utilized in addition to their anticancer effects³⁰. Recently developed tiny peptide anticancer agents and their derivatives from marine species have been widely used in medical studies. Globally, about 49 active ingredients produced from marine sources or their derivatives have either been licensed for sale or have begun clinical testing. Authorities in Europe and America have approved eleven different types of marine pharmaceuticals, four of which are employed as anticancer agents: Yondelis, Adcetric, Halverson, and Cytosar-U. A valuable biological kingdom, the marine domain is a plentiful supply of new, useful proteins and peptides. Furthermore, it is becoming an increasingly important area of medication development^31-33.

This review includes information on the development of marine-derived anticancer agents from sponges, tunicates, mollusks, soft corals, cyanobacteria, and marine microalgae, as well as medications with antiproliferative properties.

Marine anticancer agents:

The most complicated disease is cancer and can be treated with network drugs. The marine drug sources included in this review that are used as anticancer agents are Marizomib, Plinabulin Enapotamab vedotin, Coibamide A, Tisotumab vedotin, Plocabulin, Ladiratuzumab vedotin, AGS-16C3F, Pliotidepsin, Bryostatin, Pectenotoxin – 2, Lurbinectedin, Belantamab Mafodotin, Enfortumab vedotin, Polatuzumab vedotin, Trabectedin, Brentuximab vedotin, Eribulin Mesylate, and Cytarabine. Table No. 2 provides an overview of these.

Marizomib:

Marizomib is an actinomycete that possesses gram-positive bacteria with a high G + C ratio in its DNA³⁴. NPI-0052, also referred to as salinosporamide A, or marizomib, is a proteasome inhibitor that is obtained from the marine actinobacterium Slinospora tropica, which is a member of the Salinosporamide family³⁵. It is a potentially effective therapeutic drug in order to treat hematologic malignancies³⁶. Marizomib is phase I stage of development. In the clinical trial of Marizomib having relapsed or refractory multiple myeloma. The active component of marizomib is the beta lacton, and the binding of NPI-0052 is irreversible³⁷. In clinical studies, Marizomib's molecular target belongs to the monochlorinated 20s proteasome inhibitor for cancer treatment³⁸. Marizomib is an irreversible inhibitor that blocks the proteasome's beta-1, beta-2, and beta-5 subunits. At the moment, the US Food and Drug Administration (US-FDA) has not approved Marizomib³⁹.

Plinabulin:

Plinabulin, which is derived from a marine fungus and belongs to the Aspergillus species, is an alkaloid. Its molecular target is the alpha-beta tubulin protein, Plinabulin, also known as NPI-2358, is undergoing phase III clinical studies and is now being utilized to treat brain tumors and lung cancer with non-small cells. It has potent anti-microtubule properties as well. Preclinical research on plinabulin demonstrates positive safety and anticancer activity profiles. It is also evaluated for safety, pharmacokinetics, and biological activity in individuals with cancer that has spread.

Enapotam 11ab vedotin:

Enapotamab vedotin is a marine anticancer medication that is used to treat endometrial, ovarian, and cervical cancer. Its molecular target is AXL – RTK /Nectin-4, which is species-specific for mollusks and bacteria; currently conducting phase II clinical trials and enapotamab vedotin, also known as HuMax-AXL, is a new ADC conjugating with a human AXL-specific IgG1 and MMAE^40–43.

Coibamide A:

Displays a novel, highly effective anti-proliferative drug called coibamide A, which is derived from cyanobacterium. Coibamide A's molecular target is the lung cancer NCI-H460 clinical studies⁴⁴. When used in nanomolar quantities, coibamide A had a substantial cytotoxic effect on NCI-H460 lung cancer cell lines. In addition, it resulted in dose-dependent G1 cell upregulation. It has recently been evaluated against specific 60 cell lines for human malignant tumor cells of the colon, breast, and ovary. It was also shown to be more effective against the MDA-MB-231 cell line⁴⁵. One of the most popular classes of natural compounds, coibamide A directly inhibits the Sec61 protein translocan to prevent protein entry into the secretory pathway, hence causing a strong spread of cancer cells. The effect of coibamide A against human epidermal growth factor receptor [HER, ErbB] proteins in the context of lung and breast cancer cell types was assessed in the current study. Even though Coibamide A is thought to be substrate non-selective in its inhibition of the biogenesis of a wide variety of Sec61 substrate proteins⁴⁶.

Tisotumab vedotin:

Tisotumab vedotin is an antibody drug combo that targets both tissue factor and monomethyl auristatin E [MMAE], an agent that disrupts microtubules. The primary cause of it is cynobacterium. The tumor development, neoangiogenesis, and metastatic potential are hypothesized to be corrected by Tissue Factor [TF], which is actively produced in solid tumors. This is achieved by local activation of coagulation and protease activated receptor – 2 [PAR-2] signaling. It has previously been demonstrated that tisotumab vedotin activates cytotoxicity through Fc-dependent and MMAE-dependent mechanisms. Furthermore, Tisotumab vedotin inhibited PAR-2 signaling in tumor cells that wereTF-positive⁴⁷. Tisotumab vedotin provided patients with previously treated recurrent or metastatic cervical cancer with a reassuring anticancer efficacy and a convenient assurance profile. Since TF is typically significantly transmitted and identical with a poor prognosis, it works as a possible target in cervical cancer cases. Tisotumab vedotin is a first-in-class experimental antibody drug conjugate that targets TF and has shown encouraging results in solid tumors. This paper contains data from the Innova TV201 phase I/II study's cervical cancer cohort (NCT02001623)⁴⁸. The USA has approved vedotin for the treatment of metastatic cervical cancer with disease progression occurring during or following chemotherapy, based on the results of the phase II trial⁴⁹.

Plocabulin:

Phase II clinical trials are currently being conducted on plocabulin [PM060184], a polyketide that essentially fled the marine sponge and works as a new tubulin binding agent. Solid tumors are treated with it. It is a brand-new microtubule inhibitor with anticancer properties that comes from marine sources⁵⁰. The minor groove in DNA is the molecular target of Plocabulin, which is not authorized^.Recently, the molecule plocabulin was created through complete synthesis and hidden through interpretation in clinical trials involving patients with the most serious cancer disorders. It was recently reported that Plocabulin, when it comes to tubulin binding agents, has the most visible affinities, allowing tubulin dimers to be identified at a new binding site^51-52

Ladiratuzumab vedotin:

It is a sea organism called a mollusk or cyanobacterium. Ladiratuzumab vedotin belongs to the chemical class ADC [MMAE]. Ladiratuzumab vedotin targets microtubules and LIV-1 as its molecular targets. Breast cancer is treated with it⁵³. Investigative anti-LIV-1 antibody drug conjugate ladiratuzumab vedotin [LV] is linked to monomethyl auristatin E [MMAE] via a protease-cleavable linker. In metastatic triple negative breast cancer [TNBC], LIV-1 is highly expressed. Delivery of MMAE via LV has been shown to induce immunodeficiency cell death (ICD) and to drive anticancer action above cytotoxic cell assassination. In TNBC, LV monotherapy has finished its supportive activity⁵⁴. The US FDA has not yet authorized ladiratuzumab vedoti⁵⁵.

Cytarabine:

Cytarabine [Ara-C, Cytosar-U], a synthetic pyrimidine nucleoside produced from marine sources, was licensed by the Food and Drug Administration [FDA] in 1969 as a first-line treatment for leukemia⁵⁶. White blood cell cancer, or leukemia, is characterized by abnormal leukocyte proliferation and an excess of immature leukocytes. This results in a deficiency of normal white blood cells, which can produce a range of symptoms, including fever, exhaustion, repeated infections, bleeding or bruises, and even death⁵⁷. Global Cancer Statistics 2020 estimates that there are 0.3 million leukemia-related deaths and 0.5 million new cases of the disease worldwide. cytarabine was initially isolated from Tethya Crypta, a sea sponge. Cytarabine is injected into plasma, where it is metabolized by the cell's deoxycytidine kinase enzyme into the active form cytarabine triphosphate⁵⁸. The synthesis of DNA is then inhibited by cytarabine triphosphate's competition with the enzyme DNA polymerase. Additionally, the drug's integration into DNA and RNA causes cytotoxicity in the cell. Cytarabine primarily affects cells that are actively dividing by preventing the cell from moving from the G-1 phase to the S phase. All of these cause the cells that are actively dividing to die.

Brentuximab vedotin:

It is an antibody-drug conjugate [ADC] of the antimitotically active monomethyl auristatin E [MMAE], a synthetic analog of dolastatin-10, generated by cynobacteria that live in symbiosis with the sea hare Dolabella auricularia. The monoclonal antibody brentuximab is CD30-specific. In 2011, brentuximab vedotin was initially authorized for the treatment of anaplastic large T-cell systemic malignant lymphomas and Hodgkins lymphomas, one year after eribulin mesylate's approval. It inhibits tubulin polymerization [MMAE] and binds to CD30 [antibody]. Adcetris®, also known as benuximab vedotin, received approval in 2012 to treat Hodgkin’s lymphoma, a cancer form identified by elevated expression of CD⁵⁹.

Trabectidin:

In 2015, trabectidine [ET-743, Yondelis] was initially authorized for the management of ovarian cancer and soft tissue sarcoma. The natural alkaloid was first isolated from marine tunicates and, in contrast to earlier marine medications like trabectedine [Yondelis], exerts its anticancer properties through a variety of methods. It first attaches itself to the DNA double strand's minor groove. Furthermore, by disrupting microtubules and thus interfering with the late S and G2 phases of the cell cycle, it can result in cell cycle arrest. Additionally, it has the ability to cause RNA polymerase ll [RNA Pll] to degrade. By blocking the release of cytokines, it can also modify the tumor microenvironment through a variety of powerful anticancer mechanisms.

Eribulin mesylate:

The Food and Drug Administration [FDA] first approved the spongimal macrolide Eribulin mesylate, also known as Halavenas, in 2010 for the treatment of metastatic breast cancer. In 2016, the FDA approved it as the second line of treatment for liposarcoma therapy⁶⁰. Epibulin has demonstrated anticancer effect in preclinical tests on a variety of cancer types, including small cell lung cancer, ovarian cancer, pancreatic cancer, colon cancer, melanoma, and non-small cell lung cancer (NSCLC). Eribulin prevents the spread of tumors by promoting the mesenchymal-epithelial transition (MET) and blocking the epithelial-mesenchymal transition (EMT). It is an artificial variation of the marine chemical halichondrin B. This medicine functions as a microtube-targeted non-taxane one. By attaching to tubulins and microtubules in the interphase, eribulin mesylate can suppress the dynamics of centromeres and stop mitosis, which in turn causes cancer cells to undergo apoptosis and proliferate less⁶¹.

Plitidepsin:

The ascidian depsipeptide Plitidepsin [dehydrodidemnin B, Aplidin] was first approved in Australia in 2018 for the treatment of leukemia, multiple myeloma, and lymphoma. It is a naturally occurring compound that is isolated from Aplidium albican and has strong antitumor activity with low toxicity. The mechanism of Plitidepsin was achieved by targeting eukaryotic elongation factor 1A2 [eEF1A2] and subsequently inducing apoptosis in cancer cells. eEF1A2, the target of plitidepsin, is one of the two isoforms of eukaryotic elongation factor 1 [eEF1A], a protein elongation factor. During translation, aminoacyl tRNA recruitment to the ribosome can be mediated by eEF1A, an elongation factor protein. In prostate, ovarian, pancreatic, multiple myeloma, and plasmacytoma cancers, it causes cell death to demonstrate its anticancer properties. Plitidepsin can also stop the cell cycle and continuously activate the Racl/JNK pathway, in addition to causing apoptosis through G1 and G2/M arresting⁶².

Polatuzumab vedotin:

In 2019, the FDA authorized polatuzumab vedotin as a medication for the treatment of B-cell lymphomas, chronic lymphocytic leukemia, and non-Hodgkin lymphomas⁶³. This antibody-drug combination, or ADC, is made up of the monomethyl auristatin E [MMAE], a peptide toxin of symbiotic marine cynobacteria, coupled with polatuzumab, a monoclonal antibody specific to CD76b. The monomethyl auristatin E [MMAE] is specifically delivered to cancer cells by the antibody. Once the proteolytic ADC cleaves and releases the MMAE molecule, tubulin polymerization is inhibited, which ultimately results in the death of the cancer cells⁶⁴.

Enfortumab vedotin:

The FDA approved the use of enfortumab vedotin, an antibody-drug combination [ADC], to treat metastatic urothelial carcinoma by targeting the extracellular adhesion protein nectar-4. On the surface of numerous epithelial malignancies, including pancreatic, bladder, lung, and breast tumors, it is abundantly expressed. When nectin-4 is coupled to monomethyl auristatin E [MMAE], a chemotherapeutic microtubule disrupting drug, enfortumab vedotin can specifically target nectin-4-positive cells and subsequently cause cell death via MMAE⁶⁵.

AGS 16C3F:

The novel anticancer drug AGS-16C3F, is obtained from mollusks (Cyanobacterium) and is typically used to treat liver and kidney carcinomas. Astellas Pharma and Agensys establish AGS-16C3F.Targeting ENPP3 [D203a], AGS-16C3F, ADC conjugates with Monomethyl Auristatin-F [MMAF].AGS16M8F is another name for [A] AGS-16C3F. This ADC is a part of the human IgG2k monoclonal antibody [AGS-16], which has been linked to multiple myelin repair failure. Strongly inhibiting microtubules, this MMAF may have anti-tumor effects⁶⁶.

A non-cleavable maleimido caproyl [mc] linker makes AGS-16C3F an MMAF. Extracellular nucleotides are catalyzed at the ENPP3 cell surface, where they increase tumor invasion and contribute to the pathophysiology of cancer. AGS-16C3F has a strong affinity for the molecular target, ENPP3, which is seen on the surface of renal, hepatocellular, and chronic nucleogenous leukemia cells, according to preclinical trial data⁶⁷.Furthermore, anticancer activity is noted. On the other hand, 84 patients who had previously received treatment for metastatic renal cell carcinoma (mRCC) responded well to axitinib with AGS-16C3F in phase-II trials⁶⁸. After determining that AGS-16C3F was well tolerated and had clinical activity at a dose of 1.8 mg/kg every three weeks, the study's conclusion was that phase-II trials should use this dose. The discontinuation of AGS-16C3F was due to the combination of axitinib and AGS-16C3F failing to meet its primary and secondary goals^69-70.

Method No.1: Hydrolysis: Pectenotoxin-2 is hydrolyzed to yield the seco acid molecule pectenotoxin-2. Following further acylation, this molecule yields 37-O-acyl PTX-2SA, 33-O-acyl PTX-2SA, and 11-O-acyl PTX-2SA.

Method No. 2: Oxidation: Pectenotoxin-2 is oxidized step-by-step to produce pectenotoxin-1, an alcohol. This chemical is then oxidized again to produce pectenotoxin-3, an aldehyde molecule, which is oxidized even further to produce pectenotoxin-6, a carboxylic acid. Targeted Organs: Pectenotoxin-2 has been reported to exhibit specific toxicity towards P53 mutant and P53 null tumors, including highly chemoresistant variants, in addition to other actin-disrupting drugs.

Table 2: Summary on marine anticancer agent

Sr. No.	Compound name	Marine Organism	Chemical class	Molecular Target	Cancer Type	Phases
1	Marizomib	Actinobacteria	Beta- lactone	20s Proteasome inhibitor	Myeloma	Phase l
2	Plinabulin	Fungus	Alkaloid	Alpha-beta tubulin protein	Small cell lung cancer, Brain tumors.	Phase ll
3	Enapotamab vedotin	Mollusk/ Cyanobacterium	ADC [MMAE]	AXL-RTK/ Nactin-4	Ovarian cancer, Cervical cancer, Endometrial cancer.	Phase l/ll
4	Coibamide A	Cyanobacterium	Anti- proliferative depsipeptide	Sec61 substrate protein	Lung cancer, Breast cancer, Ovarian Malignant tumor.	Phase l
5	Tisotumab Vedotin	Mollusk/ Cyanobacterium	ADC[MMAE]	Tissue factor	Metastatic cervical cancer.	Phase ll
6	Plocabulin	Sponge	Polyketide	Microtubule inhibitor, Minor groove of DNA.	Solid tumors	Phase l
7	Ladiratuzumab vedotin	Mollusk/ Cyanob acterium	ADC[MMAE]	Microtubules	Breast Cancer	Phase l
8	Cytarabine	Sponge	Nucleoside	DNA Polymerase	Leukemia	Phase l
9	Eribulin	Sponge	Macrolide	Microtubules	Metastatic Breast cancer	Phase ll
10	Brentuximab Vedotin	Mollusk/ Cyanobacterium	ADC[MMAE]	CD30, Microtubules	Anaplastic large T-cell systemic Malignant lymphoma, Hodgkin”s Disease	Phase ll and l
11	Trabectidine	Tunicate	Alkaloid	Minor groove of DNA	Soft tissue sarcoma and Ovarian cancer	Phase ll
12	Plitidepsin	Tunicate	Desipeptide	eEF1A2	Multiple Myeloma, Leukemia, Lymphoma.	Phase ll/lll
13	Polatuzumab Vedotin	Mollusk/ Cyanob acterium	ADC[MMAF]	CD76b, Microtubules	Non-hodgkins lymphoma, Chroniclymphocyti leukemia, Lymphoma.	Phase lll
14	Enfortumab Vedotin	Mollusk/ Cyanob acterium	ADC[MMAE]	Nectin-4	Metastatic Urothelial Cancer	Phase l /ll
15	Ags 16 C3F	Sponge	ADC[MMAF]	ENPP3	Tumor	Phase ll

DISCUSSION:

The review emphasizes the finding of unique chemical structures and characteristics, as well as anticancer properties, in marine creatures. The issue of cytotoxicities and activity prevention of tumor development and associated chemicals that trigger apoptosis was addressed. The goal has been achieved by researching the marine population that contains bioactive compounds that have anticancer properties^.A key component of anticancer drugs is the diversity of biological materials from the marine environment, which essentially complements the marine real. The development of novel anticancer medicines derived from marine species plays a major role in increasing our understanding of the therapeutic agents developed from these organisms that target different stages of the carcinoma process. This background suggested that these anticancer drugs function through both therapeutic and preventative intervention. At the clinical level, there is an alliance of experts in medicine, chemistry, toxicology, biology, and "omics" who work together in the early stages and purposefully rely on national and international funding sources for science. They also have open access to data from earlier research project^. It seems sense that marine items could offer a platform for bettering cancer treatment approaches. Even yet, more thorough investigation is necessary to overcome the majority of typical obstacles in chemical utility. Essentially, active metabolites produced from sponges should be utilized in conjunction with cutting-edge technologies to open up new application domains that will have a significant impact on biotechnology. As drug research advances, it becomes increasingly difficult to obtain novel active metabolites from terrestrial sources, which is insufficient to keep up with the growing hazard to human health and well-being.

Natural products that are produced by enzymatic processes are provided with three-dimensional structural characteristics that enable them to combine with binding sites and exhibit both significant specificity and distinctive variety. Many viewpoints regarding how to improve natural product discovery programs in light of the increased number of pharmaceuticals made from natural materials that are reaching the market. These natural remedies have been utilized to treat human ailments and have laid a solid foundation for modern pharmaceuticals. Due to their ability to expand knowledge and their clinical significance in cancer pharmacology, these chemotherapeutic medicines have had a profound impact on the pharmacy community.

Given that cancer is one of the most serious illnesses, one may wonder, "Why are we looking forward to anticancer drugs from the deep of ocean?" which begs the question of whether finding novel marine anticancer substances is possible. The ongoing advancements in deep sea mining, extraction, and separation technologies offer fresh prospects and optimism for the discovery of marine anticancer drugs. Since a millennium ago, humans have begun to extract the active molecular component of marine substances from terrestrial sources. With increased exploration, the realm of marine flora and fauna is becoming a fascinating place to examine in order to find new anticancer leads.

CONCLUSIONS:

The current review study provides brief information of marine medications that may be used to treat different neoplastic disorders and be clinically beneficial. These medications work in different ways to treat cancer; they either destroy cancer cells or stop them from proliferating. Therefore, these biomolecules prove useful as a futuristic means of accessing combinational treatment for cancer using medications derived from marine sources. These medications can also be used in further medical research to treat other physical ailments. This review sheds light on a few anti-cancer agents that can also be assessed for their anti-cancer effects, marking a revolutionary development in cancer treatment.

ACKNOWLEDGEMENT:

The author would like to acknowledge Dr. V. K. Redasani, Principal and Director, YSPM’S YTC College of Pharmacy, Satara, for encouragement and guidance.

REFERENCE:

1. D. D. Rishipathak, A. B. Kokate, K. S. Madhawai. Activity of Quinazoline Derivatives: A Review. Asian J. Res. Pharm. Sci. 2017; 7(4): 209-211. doi: 10.5958/2231-5659.2017.00032.7

2. Pravin Kumar, Mahendra Singh Ashawat, Vinay Pandit. Gold Nanoparticle-Small Drug Molecule Conjugates: Therapeutic Applications and Benefits as Compared to Free Drug. Asian J. Pharm. Tech. 2018; 8(1): 52-62. doi: 10.5958/2231-5713.2018.00009.0

3. Baldev Krishan Sharma. Synthetic and Natural Compounds as Anti-Cancer Agents – A Review. Asian J. Research Chem., 2017; 10(5): 699-707. doi: 10.5958/0974-4150.2017.00119.5

4. Rohit Bhatia, Kiran Thapliyal, Dharmendra Kumar. Phytochemical and Therapeutic Aspects of Morinda citrifolia L. (Noni Plant) Research Journal of Pharmacognosy and Phytochemistry. 2015; 7(3).

5. Seth A.K., Shah B., Textbook of Pharmacognosy and Phytochemistry, published by Elsevier Inc. India Private Limited, 2010; 14(29): 462.

6. Faitrcloth G., Jimeno J., Rinehart K., Scheur P., Sousa- faro J.M.F., New Marine Anticancer Therapeutics- A journey from the sea to clinical trials, Mar.Drugs, 2015; 2: 15.

7. Emma Marris, Reporter for Nature Science, News Paper, Drugs From the Deep, 2006; 443.

8. Jiang S., Ke Ye, Wu L., Zhou G., Marine Power on Cancer: Drugs, Lead Compounds and Mechanisms, Mar. Drugs. 2021; 19(488): 1.

9. Newmann T., Fact checked by Isabel Godfrey, Why scientists are searching the ocean for new drugs, Medical News Today. 2019; 1.

10. Choi Y.H., Kim G.Y., Kim W.J., and Pectenotoxin-2 from marine sponges: A Potential and Anticancer Agent, Mar. Drugs. 2011; 2176-2187: 2184.

11. Jankiram N.B., Mohammad A., Rao C.V., Sea Cucumbers Metabolites as a Potent Anticancer Agents, Mar. Drugs. 2015; 2909-2923: 2910.

12. Dyshlovoy S.A., Honecker F., Marine compounds and cancer: The First Two Decades of XXI Century, Mar. Drugs. 2015; 20(1-4): 1.

13. Hemalatha C N, Anbarasu K, Vijey Aanandhi M. Evaluation of Anti-Cancer and Anti-Oxidant Activity of Cissus quandrangularis Extracts in DMBA induced Mammary Carcinomas. Research J. Pharm. and Tech. 2017; 10(1): 293-300. doi: 10.5958/0974-360X.2017.00060.9

14. B. Edwin Jose, P. Muralidharan. Effect of Azima tetracantha Lam on Human Breast Cancer Cells MCF-7. Research J. Science and Tech. 2019; 11(2): 109-112. doi: 10.5958/2349-2988.2019.00017.2

15. Raghad J. Fayyad, Alaa Naseer Mohammed Ali, Noor T. Hamdan. The Specific Anti-cancerous Mechanisms Suggesting Spirulina Alga as a Promising breast Cancer Fighter. Research Journal of Pharmacy and Technology. 2021; 14(10): 5599-2. doi: 10.52711/ 0974-360X.2021.00974

16. Bishnu Prasad Sahu, Bibekananda Meher, Biplob Kumar Dey. Exploration of Bryophytes for its Therapeutic Potential. Research J. Pharm. and Tech. 2021; 14(2): 1099-1103. doi: 10.5958/0974-360X.2021.00198.0

17. Gul-e-Saba Chaudhry, Muhammad Naveed Zafar, Yeong Yik Sung, Tengku Sifzizul Tengku Muhammad. Phytochemistry and Biological activity of Vitex rotundifolia L. Research J. Pharm. and Tech. 2020; 13(11): 5534-5538. doi: 10.5958/0974-360X.2020.00966.X

18. Rajasekhar Pinnamaneni. Cell Viability Studies and Anti-cancerous activity Evaluation of Pomegranate (Punica granatum L) extract . Research J. Pharm. and Tech. 2020; 13(1): 303-307. doi: 10.5958/0974-360X.2020.00061.X

19. Michael Lam. Beating Cancer with Natural Medicines, Library of Congress Control Number. 2003; 56.

20. Alajlani M., Al- Mousawi S.M., Chang F.R., Chen L., Elias N., El-seedi H.R., El- wahad A.A., Farag M. A.,. Goransson Ulf, Hegazy M.E.F., Iwasaki A., Khalifa S.A.M., Moustafa M.S. Musharraf S.G., Saeed A., Suenaga K., Marine Natural Products: A source of Novel Anticancer Drugs, Mar.Drugs. 2019; 17(491): 1-33.

21. Andrianasolo E., Flatt P., Gerwick W.H., McPhail K., Simmons T. L. Marine natural products as anticancer drugs. American Association for Cancer Research Journals Molecular Cancer Therapeutics. 2005; 4(2).

22. Haefner B. Drugs from the deep: Marine natural products as drug candidates. Drug Discovery Today. 2003; 8(12): 536 – 544.

23. Malve H. Exploring the ocean for new drug development: Marine Pharmacology, Journal of Pharmacy and Bioallied Sciences. 2016; 8(2): 83.

24. Liu Z.D., Wang N., Wang N., Wang T., Wang Z., Zhang B., Zhang Q.T., Zhao Y.F. Recent Advances in small peptides of Marine origin in cancer therapy, Marine Drugs. 2021; 19(2): 115.

25. Buffalo A.D, Fini M., Russo P. Deepsea as a source of novel anticancer drugs: update on discovery and preclinical/clinical evaluation in a systems medicine perspective. Experimental and Clinical Science Journal. 2015; 14: 228 – 236.

26. Anderson J.L., Assaraf Y.G., Cloos J., Jansen G., Kale A.J. Kaspersky G.J.L., Meerloo J.V., Moore B.S., Niewerth D., Riethoff L.F.V., Zweegman S., Antileukemic activity and mechanism of drug Resistance to the marine Salinospora Tropica Proteasome inhibitor Salinosporamide A [Marizomib]. American Society for Pharmacology and Experimental Therapeutics Journal.,00 Molecular Pharmacology. 2014; 86(1): 12-19.

27. Lam K.S., Potts B.C. Generating a generation of Proteasome inhibitors: From Microbial Fermentation to total Synthesis of Salinosporamide A [Marizomib] and other Salinosporamides. Marine Drugs. 2010; 8(4): 835 – 880.

28. Ali J.A., Chao T.H., Groll M., Lloyd K., Macherla V.R., Manama R.R., McArthur K.A., Neuteboom S.T.C., Palladino M.A., Palombella V.J., Potts B.C.M. Leaving groups prolong the Duration of 20s Proteasome inhibition and Enhance the Potency of Salinosporamides. Journal of Medicinal Chemistry. 2008; 51(21): 6711 – 6724.

29. Kumar S., Rajan A.M. New Investigational Drugs with Single agent activity in Multiple Myeloma. Blood Cancer Journal. 29 July 2016; 6(7): e451. Doi: 10.1038/ bcj.2016.53.

30. Cavalli A., Decherchi S., Diaz J.F., Huang L., Lloyd K., Olieric N., Perez F.D.A.B., Sala G.L., Sharma A., Steinmetz M.O., Tonra J.R., Viti F. Structure, Thermodynamics and Kinetics of PlinabulinBinding to two Tubulin Isotopes. Journal of Chemistry. 2019; 5(11): 2969 – 2986.

31. Kwok H.F., Zuo W. Development of Marine Derived Compounds for Cancer Therapy. Marine Drugs. 2021; 19(6): 342. https://doi.org/10.3390/md19060342.

32. Ashton E., Cropp G., Federico K.C., Heath E.I., Lloyd K., LoRusso P.M., Malburg L., Mita A.C., Mita M.M., Neuteboom S.T.C., Papadopoules K.P., Pilat M.J., Reich S.D., Romero O., Spear M.A., Yee L.K. Phase I first– in- human trial of the vascular Disrupting agent Plinabulin [NPI-2358] in patients with solid tumors or Lymphomas. Clinical Cancer Research. 2010; 16(23): 5892 – 5899.

33. Newman D.J. The utility of Highly toxic Marine – Sourced Compounds. Marine Drugs. 2019; 17(6): 324. https://doi.org/10.3390/md17060324.

34. Liu Z.D., Wang N., Wang N., Wang T., Wang Z., Zhang B., Zhang Q.T., Zhao Y.F. Recent Advances in small peptides of Marine origin in cancer therapy. Marine Drugs. 2021; 19(2): 115.

35. Abdelnour S., Abdo M., Alagawany M., El-Hack M.E.A., Elnesr S.S., Gabriel M.G., Khafaga A.F., Mahgoub S.A., Sakr M.A. Microalgae in modern cancer therapy. Current knowledge, Biomedicine and Pharmacotherapy Journal. 2019; 111: 42-50.

36. Badr C.E., Dolan B.P., Ishmael J.E., Kawaguchi S., Kazemi S., Mattos D.R., McPhail K.L., Moasser M.M., Oishi S., Paavilainen V.O., Saenz A.R., Serrill J.D. Targeting of HER/ErbB family proteins usingbroad spectrum Sec61 inhibitors Coibamide A and Apratoxin A. Biochemical Pharmacology. 2021; 183: 114317.

37. Alley S.C., Breij E.C., Cao A., Dominguez T., Harris J.R., Heuvel E.G.V.d., Satijin D., Velayudhan J., Verploegen S., Abstract 221: Tisotumab vedotin induces Anti- tumor activity through MMAE – mediated, Fc – mediated and Vitro. Cancer Research. 2019; 79(13 supplement): 221-221.

38. Arkenau H.T., Bono J.S.d., Coleman R.L., Concin N., Cornez N., Drew Y., Forster M.D., GennigensC., Ghatta S., Harris J.R., Hong D.S., Johnson M.L., Jones R., Lassen U.N., Machiels J.P., Rangwala R.A., Slomovitz B.M., Spicer J.F., Thistelethwaite F.C., Vergote I., Windfeld K. Tisotumab vedotin in Previously treated Recurrent or metastatic cervical cancer. Clinical Cancer Research. 2020; 26(6): 1220.

39. Markham A. Tisotumab vedotin: First Approval. Drugs. 2021; 81: 2141 – 2147.

40. Argiles G., Betrian S., Coronado C., Delord J.P., Elez E., Fudio S., Iglesias J., Macarulla T., Pita A.S.M., Roca C.G., Tabernero J., Valentin T., Zaragoza K. First – in – human phase I study of the microtubule inhibitor Plocabulin in patients with advanced solid tumors. Investigating New Drugs. 2019; 37: 674 – 683.

41. Tamanna Rai, Niranjan Kaushik, Rishabha Malviya, Pramod Kumar Sharma. A review on marine source as anticancer agents. 2024; 26(4): 415-451.

42. Andrey J.M., Aviles P., Barasoain J., Bouchet B.P., Cuevas C., Diaz J.F., Diaz M.M., Fernandez L.F.G., Galmarini C.M., Leal J.F.M., Navarro M.J.G., Pera B., PM060184, a New tubulin binding agent with potent antitumor activity including p – glycoprotein over–expressing tumors. Biochemical Pharmacology. 2014; 88(3): 291 – 302.

43. Sousa M.L.D.S. Cyanobacterial Bioactive Metabolites for anticancer drug discovers: Characterization of New compounds and molecular Mechanisms in Physiologically relevant 3D cell culture, repositorio – aberto.up.pt. 2020.

44. Almany C., Basho R., Bono V., Cortes J., Diabs S., Dillon P., Eth J., Han H.H., Kuemmel S., Meisel J., Oliveira M., O‟Shaughnessy J., Papish S., Pluard T., Reasor E.S., Sanchez L.M., Sinha R., Sterrenberg D., Tsai M., Vazquez R.V., Wang Y., Wang Z., Wuerstlein R., Abstract PD1 – 06: Open label phase 1b/2study of Ladiratuzumab vedotin in combination with pembrolizumab for First – line treatment of patients with unresectable locally – advanced or metastatic triple – negative breast cancer. Cancer Research. 2020; 80[4 supplement]: PD1 – 06 - PD1–06.

45. Sousa R.B., Tolaney S.M. Clinical Development of new Antibody – Drug conjugate in breast cancer: To infinity and Beyond. BioDrugs. 2021; 35: 159 – 174.

46. Wu L.; Ye K.; Jiang S.; Zhou G. Marine Power On Cancer: Drugs, Lead Compounds, and Mechanisms. Mar. Drugs. 2021; 19: 488, 1-19.

47. Zuo W.; Kwok H.F. Development of Marine- Derived Compounds for Cancer Therapy. Mar. Drugs. 2021; 19: 342,1-26.

48. Sung H.; Ferlay J.; Siegel R L.; Laversanne M; Soerujomataram I.; Jemal A.; Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021; 71: 209-249.

49. Kanase HR.; Singh KM. Marine Pharmacology Potential, Challenges, and Future in India. J Med Sci. 2018; 38: 49-53.

50. Jimenez PC.; Wilke DV.; Costa-Lotufo LV. Marine Drugs for Cancer: Surfacing biotechnological innovations from the oceans. Clinics. 2018; 73: 1-7.

51. Swami U.; Shah U.; Goel S. Eribulin in cancer treatment. Mar. Drugs. 2015; 13: 5016-5058.

52. Dyshlovoy S.A.; Honecker F. Marine Compounds and Cancer: updates 2020. Drugs. 2020; 18: 643,1-6.

53. Dyshlovoy S.A.; Honecker F. Marine Compounds and Cancer: The First Two Decades of XXI Century Mar. Drugs. 2019; 18(20): 1-4.

54. Deeks E.D. Polatuzumab Vedotin: First Global Approved Drugs, 2019; 79: 1467-1475.

55. Hanna K.S. Clinical Overview of Enfortumab Vedotin in the Management of Locally Advanced or Metastatic Urothelial Carcinoma. Drugs. 2019; 80: 1-7.

56. Kwok H. F., Zip W., Development of Marine Derived Compounds for Cancer Therapy, Mar. Drugs. 2021; 19(342): 1-26.

57. LouRusso P., McLaughlin J., Department of Medical Oncology, Antibody drug conjugates: Fundamentals, Drug Development and Clinical Outcomes to Target Cancer, Edited by Hurvitz S. A., Oliver Jr., K. J.

58. Chouriri T. K., Croitoru R., George S., Heng D. Y. C., Jie F., Kollamanns B. C., Poondru S., Thompson J. A. Randomised phase II study of AGS-16C3F versus Antinixib in Previously Treated Patients with Metastatic Renal Cell Carcinoma. The Oncologist. 26(3): 182- e361.

59. National Cancer Institute at National Institute of Health [cancer. gov] 49 U.S. National Library of Medicine. Clinical Trials.gov.

60. Boria P., Draisci R., Giannetti L. L., Poletti R. First report of pectenotoxin-2 [PTX-2] in algae [Dinophysis fortii] related to seafood poisoning in Europe. 1996; 34(8): 923-935.

61. Luis M. Botana. Seafood and Freshwater Toxins Pharmacology, Physiology and Detection, second edition, Toshiyuki Suzuki, Chemistry, Metabolism and chemical Detection Methods of Pectenotoxins. 343- 356.

62. M. Eastman A. Higgs H. N., Micalizio G. C., Rourke N. F. Function Oriented Studies Targeting Pectenotoxin-2: Synthesis of the GH- Ring System and Structurally Simplified Macrolactone. Org. Lett. 2017; 19: 5154- 5157.

63. R Guzmán-Guillén, M Puerto, D Gutiérrez-Praena., Potential use of chemoprotectants against the toxic effects of cyanotoxins. Toxins. 2017; 9(6): 175.

64. Ana F.C., Ana G.R., Daurte A.C., Rocha- Santos T.A.P. Clinical Trials for deriving bioactive compounds from Marine Invertebrates, Natural Products In Clinical Trials. Volume-1, edited by Rahman A., Anjum S.FRS, El-seedi H., 1-30(30).

65. Akjon L.D., Sun M.K. Bryostatin-1: Pharmacology and Therapeutic Potential as a CNS Drug Rev. Spring. 2006; 12(1): 1-8.

66. Balounovo Z., Kollar P., Pazourek J., Rajchard J. Marine Natural Products: Bryostatins in preclinical studies. Pharm Biol. 2014; 52(2): 237- 242.

67. Barraja P., Barreca M., Bertoni F., Bilela L. L., Cueto M., Deniz I., Erdogon A., Gaudencio S. P., Marrero A. P. D., Mehri M., Montalbano A., Moulin C., Petale G., Rotter A., Spano V., Taffin-de- Givenchy E., Thomas O. P., Soriano F. Marine Anticancer Agents: An overview with a particular focus on their chemical classes, Mar. Drugs. 2020; 18(619): 1-28

68. D.M., Kortmansky J., Schwartz G.K. Bryostatin-1: A novel PKC Inhibitor in Clinical Development. Cancer Investigations. 2003; 21(6): 924-936.

69. Bauermeister A., Branco P. C., Costa- Lotufo L.V., Gaudencio S. P., Jimenez P. C., Rezende- Teixeira P., Wilke D. V. Enriching cancer pharmacology with drugs of marine origin. Br. J. Pharmacol. 2020; 177: 3-27.

70. M.L. Amador, J. Jimeno, L. Paz-Ares, M. Hidalgo Progress in the development and acquisition of anticancer agents from marine Sources. 2003; 14(11): 1607-1615.

Received on 25.04.2024 Revised on 06.06.2024

Accepted on 19.07.2024 Published on 07.12.2024

Available online on December 30, 2024

Res.J. Pharmacology and Pharmacodynamics.2024;16(4):306-314.

DOI: 10.52711/2321-5836.2024.00053