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Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population within the tumor that have recently come into the spotlight. By extracellular matrix (ECM) remodeling and robust cross-talk with cancer cells via different secretions such as cytokines, chemokines, and growth factors, CAFs contribute to cancer progression and poorer prognoses in patients. Novel candidates have been developed to inhibit CAFs; however, due to safety and efficacy issues, none have successfully passed clinical trials. Despite these shortcomings, one concept embraced by many researchers is to repurpose non-oncology drugs with potential anti-cancer properties for cancer treatment. One such example is pirfenidone (PFD), an oral anti-fibrotic medication, primarily administered for idiopathic pulmonary fibrosis. Emerging evidence suggests that PFD has promising anti-cancer effects, mainly manifesting through targeting CAFs. With inhibitory effects on CAFs, PFD restricts cancer proliferation, metastasis, immunosuppression, drug resistance, and tumor stiffness. To improve efficacy and minimize adverse effects, several innovative approaches have been proposed for targeting CAFs via PFD. Interestingly, combination therapy comprising PFD and chemotherapeutics e.g. doxorubicin has shown synergistic anti-cancer effects while protecting normal tissue. Furthermore, novel drug delivery systems, e.g. biomimetic liposomes and multilayer core-shell nanoparticles, have enhanced the pharmacokinetic properties of PFD and further increased its intratumoral delivery. Single-cell RNA sequencing (scRNA-seq) has also been suggested to characterize different subpopulations of CAFs and design precise PFD-based therapeutic strategies. Herein, we discuss the promising anti-cancer effects of PFD via inhibition of CAFs. We then provide findings on novel PFD-based approaches to target CAFs using combination therapy, nanocarrier-based drug delivery, and scRNA-seq. • Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) have recently gained attention. • Several novel candidates have been developed to inhibit these fibroblasts. • Many researchers are now exploring repurposing of non-oncology drugs for cancer treatment. • We discuss the promising anti-cancer effects of PFD via inhibition of CAFs. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is one of the most aggressive brain and spinal cord tumors. Despite the significant development in application of antitumor drugs, no significant increases have been observed in the survival rates of patients with GBM, as GBM cells acquire resistance to conventional anticancer therapeutic agents. Multiple studies have revealed that PI3K/Akt, MAPK, Nanog, STAT 3, and Wnt signaling pathways are involved in GBM progression and invasion. Besides, biological processes such as anti-apoptosis, autophagy, angiogenesis, and stemness promote GBM malignancy. Resveratrol (RESV) is a non-flavonoid polyphenol with high antitumor activity, the potential of which, regulating signaling pathways involved in cancer malignancy, have been demonstrated by many studies. Herein, we present the potential of RESV in both single and combination therapy- targeting various signaling pathways- which induce apoptotic cell death, re-sensitize cancer cells to radiotherapy, and induce chemo-sensitizing effects to eventually inhibit GBM progression. [ABSTRACT FROM AUTHOR]

• Melatonin can regulate the immune system function that may be useful for cancer therapy. • Melatonin blunts the proliferation and activity of immunosuppressive cells in the tumour. • The immunomodulatory effects of melatonin within the tumour may boost the anti-tumour immunity. • The attenuation of inflammatory and anti-inflammatory responses in normal tissues by melatonin can protect against the early and late effects of cancer therapy. Immune system interactions within the tumour have a key role in the resistance or sensitization of cancer cells to anti-cancer agents. On the other hand, activation of the immune system in normal tissues following chemotherapy or radiotherapy is associated with acute and late effects such as inflammation and fibrosis. Some immune responses can reduce the efficiency of anti-cancer therapy and also promote normal tissue toxicity. Modulation of immune responses can boost the efficiency of anti-tumour therapy and alleviate normal tissue toxicity. Melatonin is a natural body agent that has shown promising results for modulating tumour response to therapy and also alleviating normal tissue toxicity. This review tries to focus on the immunomodulatory actions of melatonin in both tumour and normal tissues. We will explain how anti-cancer drugs may cause toxicity for normal tissues and how tumours can adapt themselves to ionizing radiation and anti-cancer drugs. Then, cellular and molecular mechanisms of immunoregulatory effects of melatonin alone or combined with other anti-cancer agents will be discussed. [ABSTRACT FROM AUTHOR]