Over the past few decades, the life expectancy of humankind has increased significantly due to advancements in life sciences and medical research, particularly given our increasing success in the epidemiological and pharmacological management of bacterial, fungi, and viral infections. However, the number of new cancer cases has increased due to this extended longevity. At present, cancer is one of the major causes of death worldwide; several factors contribute to the growing numbers in global cancer statistics, including genetic determinants, increased exposure to carcinogens, and the nutritional conditions of modern life.
Despite the noteworthy advances in the field, unresponsiveness, recidivism, side effects, and drug resistance are still obstacles to overcome in cancer treatment. Furthermore, the high cost of current therapies poses a significant problem for the public health systems in several countries, limiting patients’ access to the most recent drugs and therapeutic approaches. Conversely, significant advances have been made toward molecular aspects of tumor biology in the last decade(s), enabling researchers to foresee new avenues of cancer treatment with the aid of novel drugs/targets and innovative approaches, which must be brought to the attention of physicians and their patients.
Scientists worldwide are focused on understanding the molecular aspects of tumorigenesis, cancer progression, and metastasis. However, cancer treatment remains a very challenging task, as it depends on the intrinsic features of the disease (type, location, stage, mutations, responsiveness, and so on) and the conditions and variability among patients (comorbidities, immune system, and others). All these variables pose additional challenges for researchers and clinicians. Thus, the path from the bench to the bedside is long and includes multiple stages, from basic and preclinical studies to clinical trials.
It is well established that cancer cells exhibit a myriad of molecular alterations and adaptive transformations, enabling them to have unlimited proliferative capacity and invasiveness [1]. Furthermore, such alterations allow tumor cells to escape the regulatory mechanisms of cell growth/death and evade recognition/destruction by the immune system. All these features are elicited or accompanied by metabolic reprogramming, gene/protein expression changes, and alterations in several signaling pathways. Based on this, a vast therapeutic arsenal is now available for cancer treatment, varying from old cytotoxic drugs to the current personal precision oncology [2]. Cancer therapy now includes conventional chemotherapy, photodynamic therapy, inhibitors of angiogenesis, targeted therapy, immunotherapy, CAR-T cell therapy, oncolytic viruses, and antitumor vaccines [3,4]. Additionally, combined therapies, the development of second- and third-generation drugs, nanotechnological approaches, and drug repurposing have arisen as possible strategies to improve drug responsiveness and overcome drug resistance [5,6,7,8,9]. At last, the possibility of genome edition/correction by the CRISPR-Cas9 methodology represents a promising tool to be employed in treating cancer in the near future [10].
Notably, the improvement of analytical methods and experimental capabilities catalyzed the current advancements in the field of molecular oncology. These advancements are pivotal to discovering novel targets and drugs for cancer treatment. Among such novel strategies, the screening of new molecules represents a prospective approach for drug discovery, helping to overcome drug resistance [11,12,13]. Furthermore, identifying oncogenes and their regulation by miRNAs and epigenetic alterations enable the discovery of new biomarkers for cancer diagnosis, paving the way for new therapeutic opportunities [14,15]. The modulation of PD-L1 expression/activity is also a promising therapeutic strategy [16].
I am, therefore, pleased to introduce the papers published in this Special Issue, “State-of-the-Art Molecular Oncology in Brazil”. These manuscripts represent a sampling of the ongoing studies conducted in Brazil in the field of cancer research, and are also a tribute to the high-quality research developed in the country in spite of the severe restrictions imposed on research funding in recent years. I would also like to thank all authors for their valuable contributions, and the reviewers who took part in the peer-review process. Finally, I hope the audience worldwide will enjoy the new information and discussions provided by this Special Issue.
Conflicts of Interest
The author declares no conflict of interest.
Footnotes
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References
- 1.Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013. [DOI] [PubMed] [Google Scholar]
- 2.Schirrmacher V. From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review) Int. J. Oncol. 2019;54:407–419. doi: 10.3892/ijo.2018.4661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.De Campos N.S.P., De Oliveira Beserra A., Pereira P.H.B., Chaves A.S., Fonseca F.L.A., Da Silva Medina T., Dos Santos T.G., Wang Y., Marasco W.A., Suarez E.R. Immune Checkpoint Blockade via PD-L1 Potentiates More CD28-Based than 4-1BB-Based Anti-Carbonic Anhydrase IX Chimeric Antigen Receptor T Cells. Int. J. Mol. Sci. 2022;23:5448. doi: 10.3390/ijms23105448. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Yang J., Chen Y., Jing Y., Green M.R., Han L. Advancing CAR T cell therapy through the use of multidimensional omics data. Nat. Rev. Clin. Oncol. 2023;20:211–228. doi: 10.1038/s41571-023-00729-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Crocamo S., Binato R., Dos Santos E.C., De Paula B., Abdelhay E. Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast Cancer. Int. J. Mol. Sci. 2022;23:15515. doi: 10.3390/ijms232415515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Da Silva-Oliveira R.J., Gomes I.N.F., Da Silva L.S., Lengert A.V.H., Laus A.C., Melendez M.E., Munari C.C., Cury F.P., Longato G.B., Reis R.M. Efficacy of Combined Use of Everolimus and Second-Generation Pan-EGRF Inhibitors in KRAS Mutant Non-Small Cell Lung Cancer Cell Lines. Int. J. Mol. Sci. 2022;23:7774. doi: 10.3390/ijms23147774. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.De Mello J.C., Moraes V.W.R., Watashi C.M., Da Silva D.C., Cavalcanti L.P., Franco M.K.K.D., Yokaichiya F., De Araujo D.R., Rodrigues T. Enhancement of Chlorpromazine Antitumor Activity by Pluronics F127/L81 Nanostructured System against Human Multidrug Resistant Leukemia. Pharmacol. Res. 2016;111:102–112. doi: 10.1016/j.phrs.2016.05.032. [DOI] [PubMed] [Google Scholar]
- 8.Moraes V.W.R., Santos V.M., Suarez E.R., Ferraz L.S., Lopes R.M., Mognol G.P., Campeiro J.D., Machado-Neto J.A., Nascimento F.D., Hayashi M.A.F., et al. Targeting Ca2+ and Mitochondrial Homeostasis by Antipsychotic Thioridazine in Leukemia Cells. Life. 2022;12:1477. doi: 10.3390/life12101477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Dias e Silva D., Borba G.B., Beal J.R., Botrus G., Osawa A., Araújo S.E.A., Moura F., Guendelmann R.A.K., Uson Junior P.L.S. Response to Abemaciclib and Immunotherapy Rechallenge with Nivolumab and Ipilimumab in a Heavily Pretreated TMB-H Metastatic Squamous Cell Lung Cancer with CDKN2A Mutation, PIK3CA Amplification and TPS 80%: A Case Report. Int. J. Mol. Sci. 2023;24:4209. doi: 10.3390/ijms24044209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Stefanoudakis D., Kathuria-Prakash N., Sun A.W., Abel M., Drolen C.E., Ashbaugh C., Zhang S., Hui G., Tabatabaei Y.A., Zektser Y., et al. The Potential Revolution of Cancer Treatment with CRISPR Technology. Cancers. 2023;15:1813. doi: 10.3390/cancers15061813. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Bonturi C.R., Silva Teixeira A.B., Rocha V.M., Valente P.F., Oliveira J.R., Filho C.M.B., Fátima Correia Batista I., Oliva M.L.V. Plant Kunitz Inhibitors and Their Interaction with Proteases: Current and Potential Pharmacological Targets. Int. J. Mol. Sci. 2022;23:4742. doi: 10.3390/ijms23094742. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.De Sousa Portilho A.J., Da Silva E.L., Bezerra E.C.A., Moraes Rego Gomes C.B.S., Ferreira V., De Moraes M.E.A., Da Rocha D.R., Burbano R.M.R., Moreira-Nunes C.A., Montenegro R.C. 1,4-Naphthoquinone (CNN1) Induces Apoptosis through DNA Damage and Promotes Upregulation of H2AFX in Leukemia Multidrug Resistant Cell Line. Int. J. Mol. Sci. 2022;23:8105. doi: 10.3390/ijms23158105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Lesbon J.C.C., Garnica T.K., Xavier P.L.P., Rochetti A.L., Reis R.M., Müller S., Fukumasu H. A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates. Int. J. Mol. Sci. 2022;23:11911. doi: 10.3390/ijms231911911. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Cuzziol C.I., Marzochi L.L., Possebon V.S., Kawasaki-Oyama R.S., Mattos M.F., Junior V.S., Ferreira L.A.M., Pavarino E.C., Castanhole-Nunes M.M.U., Goloni-Bertollo E.M. Regulation of VEGFA, KRAS, and NFE2L2 Oncogenes by MicroRNAs in Head and Neck Cancer. Int. J. Mol. Sci. 2022;23:7483. doi: 10.3390/ijms23137483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Murta C.B., Furuya T.K., Carrasco A.G.M., Uno M., Sichero L., Villa L.L., Faraj S.F., Coelho R.F., Guglielmetti G.B., Cordeiro M.D., et al. miRNA and mRNA Expression Profiles Associated with Lymph Node Metastasis and Prognosis in Penile Carcinoma. Int. J. Mol. Sci. 2022;23:7103. doi: 10.3390/ijms23137103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Dias J.M., Santana I.V.V., Da Silva V.D., Carvalho A.L., Arantes L.M.R.B. Analysis of Epstein-Barr Virus (EBV) and PD-L1 Expression in Nasopharyngeal Carcinoma Patients in a Non-Endemic Region. Int. J. Mol. Sci. 2022;23:11720. doi: 10.3390/ijms231911720. [DOI] [PMC free article] [PubMed] [Google Scholar]