Current Chemical Biology - Volume 15, Issue 1, 2021

The ubiquitin proteasome system (UPS) is a crucial protein degradation pathway that involves several enzymes to maintain cellular protein homeostasis. This system has emerged as a major drug target against certain types of cancer as a disruption at the cellular level of UPS enzyme components forces the transformation of normal cell into cancerous cell. Although enormous advancements have been achieved in the understanding of tumorigenesis, efficient cancer therapy remains a goal towards alleviating this serious health issue. Since UPS has become a promising target for anticancer therapies, herein, we provide comprehensive review of the ubiquitin proteasome system as a significant process for protein degradation. Herein, the anti-cancer therapeutic potential of this pathway is also discussed.

Background: The term “hematological malignancy” means a cluster of cancer and tumor conditions, including leukemia, lymphoma, myeloproliferative neoplasm, lymphoproliferative disorders, etc., involved with circulatory organs like blood, bone marrow, lymph, and lymph nodes. Introduction: The increase in the number of hematological malignancy-related cases in our modern society urges suitable treatment of such disease. In this current era, there is still a major deficiency in the number of suitable chemotherapeutic agents for the treatment of hematological malignancies. Methods: The researchers were successful in identifying various cellular, extracellular proteins, and cytokines, as well as their involvement in different hematological malignancies via epigenetic modulation and regulation of other proteins and signaling pathways. Here, we have discussed the structural aspects, connection, and pathophysiological contributions of a group of different cellular and extracellular proteins that are regulated and/or have a significant influence on the progression of different hematological malignancies along with their potent inhibitors. Result and Conclusion: The correlation of physiological proteins with cancerous hematological conditions has been discussed here. It can be crucial for the development of potent inhibitors as chemotherapeutic agents to contest such malignancies. This review will also be useful in the chemotherapeutic agent development by providing crucial information about such hematological malignancy-related proteins and their inhibitors. The repurposed drugs with potential for anticancer applications are also discussed.

Prostaglandin E2 (PGE2) is involved in several biological processes, including inflammation, pain, fever, renal function, mucosal integrity, angiogenesis and tumor growth. PGE2 receptor subtypes (EP1-4) play pivotal roles in PGE2-mediated biological events. Recent studies revealed the fact that EP4 is commonly upregulated in cancer to stimulate cell proliferation, migration, invasion, and metastasis. Additionally, the EP4 receptor has a role in several anti-inflammatory processes, bone formation and hemostasis. EP4 receptor modulators can be used as drugs of specific interest. A number of EP4 receptor agonists and antagonists are at different stages of clinical development. The agonists of EP4 receptor showed promising results for ulcerative colitis (UC), bone deposition and facilitated bone resorption. The uses of EP4 antagonists, particularly in combination with chemotherapy, endocrine therapy, or immune-based therapies, may be the treatment options for cancer. Several EP4 antagonists are being progressed in clinical trials and hopefully, the results will show the usefulness of EP4 receptor as a target for cancer therapeutics. In this review, we have summarized the EP4 receptor and the possible therapeutic applications of EP4 receptor- selective agonists and antagonists.

Breast cancer is the most common and highly heterogeneous neoplastic disease comprised of several subtypes with distinct molecular etiology and clinical behaviours. The mortality observed over the past few decades and the failure in eradicating the disease is due to the lack of specific etiology, molecular mechanisms involved in the initiation and progression of breast cancer. Understanding of the molecular classes of breast cancer may also lead to new biological insights and eventually to better therapies. The promising therapeutic targets and novel anti-cancer approaches emerging from these molecular targets that could be applied clinically in the near future are being highlighted. In addition, this review discusses some of the details of current molecular classification and available chemotherapeutics.

Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to a number of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signaling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

The advancements in cancer treatment have no significant effect on ovarian cancer [OC]. The lethality of the OC remains on the top list of gynecological cancers. The long term survival rate of the OC patients with the advanced stage is less than 30%. The only effective measure to increase the survivability of the patient is the detection of disease in stage I. The earlier the diagnosis, the more will be the chances of survival of the patient. But due to the absence of symptoms and effective diagnosis, only a few % of OC are detected in stage I. A valid, reliable having a high acceptance test is imperative to detect OC in its early stages. Currently, the most used approach for the detection of OC is the screening of CA-125 and transvaginal ultrasonography together. This approach has an efficacy of only 30-45%. A large number of biomarkers are also being explored for their potential use in the early screening of OC, but no success is seen so far. This review provides an overview of the biomarkers being explored for early-stage diagnosis of OC and increasing the current long-term survival rates of OC patients.