Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium

Abstract

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the first modern therapeutic approach in medical oncology. However, a real breakthrough took place after the Second World War, with the discovery of cytotoxic antitumor drugs and the birth of chemotherapy for the treatment of various hematological and solid tumors. Starting from this epochal turning point, there has been an exponential growth of studies concerning the use of new drugs for cancer treatment. The second fundamental breakthrough in the field of oncology and pharmacology took place at the beginning of the ‘80s, thanks to molecular and cellular biology studies that allowed the development of specific drugs for some molecular targets involved in neoplastic processes, giving rise to targeted therapy. Both chemotherapy and target therapy have significantly improved the survival and quality of life of cancer patients inducing sometimes complete tumor remission. Subsequently, at the turn of the third millennium, thanks to genetic engineering studies, there was a further advancement of clinical oncology and pharmacology with the introduction of monoclonal antibodies and immune checkpoint inhibitors for the treatment of advanced or metastatic tumors, for which no effective treatment was available before. Today, cancer research is always aimed at the study and development of new therapeutic approaches for cancer treatment. Currently, several researchers are focused on the development of cell therapies, anti-tumor vaccines, and new biotechnological drugs that have already shown promising results in preclinical studies, therefore, in the near future, we will certainly assist to a new revolution in the field of medical oncology.

Platinum Derivatives Effects on Anticancer Immune Response

“…Cisplatin, carboplatin and oxaliplatin, the main platinum derivatives used in clinic, share similarities in their structure but also have differences in their mode of action (transport or DNA modifications for example) and are not used for the treatment of the same types of cancers (Table 1). CTR1 [58] ATP7B [60] Passive absorption [61] CTR1 [58,60] OCT1, OCT2 [60] Na + , K + -ATPase pump [60] MATEs [62] DNA Adducts Intra-strand and less frequently inter-strand connections [60] Fewer intra-strand and less frequently inter-strand connections than with cisplatin at equimolar concentrations [60,63] Intra and inter-strand connections more stable and inducing a more important DNA distortion [60] Repair Mechanisms NER and MMR [64,65] NER and MMR [65] NER [65] Type of Cancer Ovary, testis, bladder, colon, rectum, lung or head and neck cancers [66] Ovary, lung and ENT Reduced efficacy in testis, bladder and epidermoid head and neck cancers [67] Stage II/III colon cancers, metastatic colorectal cancers and NSCLCs [68] Side Effects Nausea, vomiting, nephrotoxicity, myelosuppression (thrombocytopenia, leucopenia, anemia) and peripheral sensory neuropathy (ototoxicity) [64] Less important neurotoxicity and ototoxicity than cisplatin Serious myelosuppression strong thrombocytopenia, neutropenia and anemia [60,66] Sensorial neuropathy but no hepatic or kidney toxicity [69] 3.1. Cisplatin…”

“…Ovary, testis, bladder, colon, rectum, lung or head and neck cancers [66] Ovary, lung and ENT Reduced efficacy in testis, bladder and epidermoid head and neck cancers [67] Stage II/III colon cancers, metastatic colorectal cancers and NSCLCs [68] Side Effects Nausea, vomiting, nephrotoxicity, myelosuppression (thrombocytopenia, leucopenia, anemia) and peripheral sensory neuropathy (ototoxicity) [64] Less important neurotoxicity and ototoxicity than cisplatin Serious myelosuppression strong thrombocytopenia, neutropenia and anemia [60,66] Sensorial neuropathy but no hepatic or kidney toxicity [69]…”

Immunoinformatic design of multi epitopes peptide-based universal cancer vaccine using matrix metalloproteinase-9 protein as a target

“…The core epitopes (KMLLFSGRRLWRFDV) is thought to be the top binder as it interacts with 18 alleles; (HLA-DRB1*01:01,HLA-DRB1*03:01,HLA-DRB1*04:02,HLA-DRB1*07:01,HLA-DRB1*04:04,HLA-DRB1*08:01,HLA-DRB1*09:01,HLA-DRB1*13:01,HLA-DRB1*11:01,HLA-DRB1*13:02,HLA-DRB1*12:01,HLA-DRB1*15:01,HLA-DRB1*16:02,HLA-DRB3*01:01,HLA-DRB4*01:03,HLA-DRB5*01:01,HLA-DRB3*03:01,HLA-DRB4*01:01). Followed by (GRGKMLLFSGRRLWR, RGKMLLFSGRRLWRF,GKMLLFSGRRLWRFD,TFTRVYSRDADIVIQ, AVIDDAFARAFALWS,FARAFALWSAVTPLT,MLLFSGRRLWRFDVK, GNQLYLFKDGKYWRF, NQLYLFKDGKYWRFS) which binds to (17, 17, 18, 14, 14, 17, 15, 14, 14) alleles. (Table 4).…”

“…Different type of immunotherapy are available including cytokine therapy, checkpoint inhibitors, monoclonal antibodies and therapeutic vaccines. (13, 14) With the latter being the center of many researches in the recent years, cumulating in the approving of Sipuleucel-T By the U.S. Food and Drug Administration (FDA) as the first dendritic cell based therapeutic vaccine for prostate cancer in 2010. (15, 16) vaccine can either be used alone or in combination with other modalities like immune checkpoint inhibitors (ICIs) which shows better results when compared with vaccine monotherapy.…”

Phytochemicals based chemopreventive and chemotherapeutic strategies and modern technologies to overcome limitations for better clinical applications

“…This observation led researchers to propose that actively dividing cancer cells may also be killed similarly by using such chemical compounds. Clinical data suggested that mustard gas suppress the division of cells of certain types of cancers such as leukemia and lymphomas (Falzone, Salomone, & Libra, 2018). For the past few decades, clinicians have emphasized to use a combinatorial approach to treat cancer where more than one anticancer drug is administered simultaneously and may be used as an adjuvant or neoadjuvant strategy (Cheng, Yang, & Shyur, 2016).…”