Breast cancer is the most prevalent cancer in women worldwide. Triple‑negative breast cancer (TNBC) is characterized by the lack of expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. It is the most aggressive subtype of breast cancer and accounts for 12‑20% of all breast cancer cases. TNBC is associated with younger age of onset, greater metastatic potential, higher incidence of relapse, and lower overall survival rates. Based on molecular phenotype, TNBC has been classified into six subtypes (BL1, BL2, M, MES, LAR, and IM). TNBC treatment is challenging due to its heterogeneity, highly invasive nature, and relatively poor therapeutics response. Chemotherapy and radiotherapy are conventional strategies for the treatment of TNBC. Recent research in TNBC and mechanistic understanding of disease pathogenesis using cutting‑edge technologies has led to the unfolding of new lines of therapies that have been incorporated into clinical practice. Poly (ADP‑ribose) polymerase and immune checkpoint inhibitors have made their way to the current TNBC treatment paradigm. This review focuses on the classification, features, and treatment progress in TNBC. Histological subtypes connected to recurrence, molecular classification of TNBC, targeted therapy for early and advanced TNBC, and advances in non‑coding RNA in therapy are the key highlights in this review.

Resveratrol is one of the most widely studied bioactive plant polyphenols which possesses anticancer properties. Previously we have reported synthesis, characterization and identification of a novel resveratrol analog, SS28. In the present study, we show that SS28 induced cytotoxicity in several cancer cell lines ex vivo with an IC₅₀ value of 3–5 μM. Mechanistic evaluation of effect of SS28 in non-small cell lung cancer cell line (A549) and T-cell leukemic cell line (CEM) showed that it inhibited Tubulin polymerization during cell division to cause cell cycle arrest at G2/M phase of the cell cycle at 12–18 h time period. Immunofluorescence studies confirmed the mitotic arrest upon treatment with SS28. Besides, we show that SS28 binds to Tubulin with a dissociation constant of 0.414 ± 0.11 μM. Further, SS28 treatment resulted in loss of mitochondrial membrane potential, activation of Caspase 9 and Caspase 3, leading to PARP-1 cleavage and finally cell death via intrinsic pathway of apoptosis. Importantly, treatment with SS28 resulted in regression of tumor in mice. Hence, our study reveals the antiproliferative activity of SS28 by disrupting microtubule dynamics by binding to its cellular target Tubulin and its potential to be developed as an anticancer molecule.

Background: Curcumin is known for its multitude of medicinal properties, including anti-cancer and migrastatic activity. Efforts to overcome poor bioavailability, stability, and side effects associated with the higher dose of curcumin has led to the development of newer derivatives of curcumin. Thus, the focus of this study is to screen novel curcumin derivatives, namely ST03 and ST08, which have not been reported before, for their cytotoxicity and migrastatic property on cancer cells. Methods: Anti-cancer activity of ST03 and ST08 was carried out using standard cytotoxicity assays viz., LDH, MTT, and Trypan blue on both solid and liquid cancer types. Flow cytometric assays and western blotting was used to investigate the cell death mechanisms. Transwell migration assay was carried out to check for migrastatic properties of the compounds. Results: Both the compounds, ST03 and ST08, showed ~ 100 fold higher potency on liquid and solid tumour cell lines compared to its parent compound curcumin. They induced cytotoxicity by activating the intrinsic pathway of apoptosis in the breast (MDA-MB-231) and ovarian cancer cell lines (PA-1) bearing metastatic and stem cell properties, respectively. Moreover, ST08 also showed inhibition on breast cancer cell migration by inhibiting MMP1 (matrix metalloproteinase 1). Conclusion: Both ST03 and ST08 exhibit anti-cancer activity at nanomolar concentration. They induce cell death by activating the intrinsic pathway of apoptosis. Also, they inhibit migration of the cancer cells by inhibiting MMP1 in breast cancer cells.

NonhomologousDNAend joining (NHEJ) is the majorDNAdouble‐strand break (DSB) repair pathway in mammals. Previously, we have described a small molecule inhibitor,SCR7, which can inhibitNHEJin a LigaseIV‐dependent manner. Administration ofSCR7 within the cells resulted in the accumulation ofDNAbreaks, cell death, and inhibition of tumor growth in mice. In the present study, we report that parentalSCR7, which is unstable, can be autocyclized into a stable form. Both parentalSCR7 and cyclizedSCR7 possess the same molecular weight (334.09) and molecular formula (C₁₈H₁₄N₄OS), whereas its oxidized form,SCR7‐pyrazine, possesses a different molecular formula (C₁₈H₁₂N₄OS), molecular weight (332.07), and structure. While cyclized form ofSCR7 showed robust inhibition ofNHEJin vitro, both forms exhibited efficient cytotoxicity. Cyclized and oxidized forms ofSCR7 inhibitedDNAend joining catalyzed by LigaseIV, whereas their impact was minimal on LigaseIII, Ligase I, and T4DNALigase‐mediated joining. Importantly, both forms inhibited V(D)J recombination, although the effect was more pronounced forSCR7‐cyclized. Both forms blockedNHEJin a LigaseIV‐dependent manner leading to the accumulation ofDSBs within the cells. Although cytotoxicity due toSCR7‐cyclized was LigaseIVspecific, the pyrazine form exhibited nonspecific cytotoxicity at higher concentrations in LigaseIV‐null cells. Finally, we demonstrate that both forms can potentiate the effect of radiation. Thus, we report that cyclized and oxidized forms ofSCR7 can inhibitNHEJin a LigaseIV‐dependent manner, althoughSCR7‐pyrazine is less specific to LigaseIVinside the cell.