Despite their effectiveness as a crucial component of combination chemotherapy regimens against solid tumors, platinum compounds have many serious side effects that limit their use. This review article focuses on the various toxic effects of platinum compounds in cancer patients and the mechanisms of toxicity associated with each of these toxic effects. It also describes the future directions for developing novel platinum compounds, using both animal and human studies. The reference lists of relevant publications were included after searching the Google and Google Scholar databases, PubMed, and scientific journals. It focuses primarily on trials that were published between 2005 and 2020. Platinum-based medicines, as a soft nucleophile, can freely bind to peptides and proteins containing sulfur residues from thiol-containing amino acids like cysteine and methionine, as well as the antioxidant peptide glutathione. Platinum medicines, on the other hand, are primarily directed at nuclear DNA. Platinum medicines bind to normal cells as well as malignant cells, particularly those in fast growing tissues, causing a variety of dangerous side effects. Fast-growing tissues such as the mucous membranes of the mouth, throat, stomach, and intestines, bone marrow, and hair follicles can be damaged by cytotoxic chemotherapy drugs, resulting in gastrointestinal toxicities, myelosuppression, and hair loss. Platinum compounds also cause nephrotoxicity and hepatotoxicity, which are well-known side effects. Current platinum-based chemotherapy treatments have been restricted in the last decade, prompting a search for novel platinum-based medications with mechanisms of action distinct from those of existing chemotherapeutics.

Objective The present study was designed to investigate the possible synergistic effects of melatonin with zinc in the prevention and treatment of oxaliplatin-induced neurotoxicity in rats. Methodology Forty-eight male Wistar albino rats were used and randomly allocated into six groups: The negative control group, oxaliplatin group, zinc + oxaliplatin group, melatonin + oxaliplatin group, zinc + melatonin + oxaliplatin prevention-approach group, and zinc + melatonin + oxaliplatin treatment-approach group. The thermal nociceptive/hyperalgesia tests were performed. Brain tissue homogenate was used for measuring GFAP, NCAM, TNF α, MAPK 14, NF-kB, GPX, and SOD. Brain tissue was sent for histopathological and immunohistochemistry studies. Results The combination therapies showed improvement in the behavioral tests. A significant increase in GPX and SOD with a significant decrease in GFAP levels resulted in the prevention approach. TNF α decreased significantly in the treatment approach. No significant changes were seen in NCAM, NFkB, and MAPK-14. The histopathological findings support the biochemical results. Additionally, immunohistochemistry revealed a significant attenuation of p53 and a non-significant decrease in Bcl2 levels in the combination groups. Conclusion The combination of zinc with melatonin for the prevention approach was effective in attenuating neurotoxicity induced by oxaliplatin. The proposed mechanisms are boosting the antioxidant system and attenuating the expression of p53, GFAP, and TNF-α.

Breast cancer has the highest prevalence of all cancers in females, with roughly 2.26 million new cases diagnosed and an estimated 0.68 million deaths/year. Hormone receptor-positive (HR+) or human epidermal growth factor receptor-negative (HER2-) illness affects the vast majority of patients with metastatic breast cancer (MBC). Endocrine therapy (ET) with aromatase inhibitors (AIs) is the preferred first-line choice for this subpopulation. However, because most patients developed tolerance to these medications, demand for alternate endocrine regimens has surged. Inhibition of cyclin-dependent kinase 4 and 6 (CDK4/6) is proving to be a success in resistant patients as well as a first-line treatment. This review article highlights the current indications for CDK4/6 inhibitors in breast cancer that have been approved by the FDA. The literature search was confined to the years 2015 to 2020, and 27 articles and 6 studies were chosen for further research from a large number of publications. In hormone receptor-positive, HR RC+, HER2- advanced or metastatic breast cancer (ABC/MBC) patients, the use of currently available CDK4/6 inhibitors, either alone (abemaciclib) or in combination with endocrine therapy (Palbociclib and Ribociclib), showed a beneficial effect when compared to endocrine therapy alone. The use of CDK4/6 inhibitors resulted in longer progression-free survival (PFS), greater clinical benefit rates (CBR), and an overall response rate (ORR), as well as an overall survival (OS) advantage in patients previously treated with endocrine treatment (ET).

Oncologists considered platinum-based medicines as potent cytotoxic agents. Despite their efficacy in combination chemotherapy regimens for many solid tumors, they have many substantial side effects that limit their use. There is no known prophylactic strategy for platinum drugs-induced neurotoxicity, which limit a therapeutic dose benefit. This review highlights the etiology of platinum-drugs-induced neuropathy, and covers the preventative and therapeutic options for cancer patients. It focuses on clinical studies conducted between 2010 and 2020. Loss of functional indications such as touch, vibration and joint location, as well as diminished or missing deep tendon reflexes in the upper and lower limbs are all markers of neurotoxicity. These side effects may last for months or years after treatment, lower quality of life, and creating a substantial survivorship issue. DNA damage, oxidative stress, mitochondrial dysfunction, dysregulation of intracellular signaling, impairment of voltage gated ion channel function, and neuro-inflammation have all been proposed as mechanisms for chemotherapy-induced peripheral neuropathy (CIPN). There are no proven pharmaceutical or nutritional therapies to prevent CIPN. Several anti-CIPN medications have been investigated, but either had no effect or had an effect in a limited sample study. Supportive care medications such anti-epileptics and antidepressants are used to treat CIPN.