Poly(ADP-ribosyl)ation (PARylation), a type of post-translational modification catalyzed by poly(ADP-ribose) polymerase (PARP), is implicated in numerous biological processes including DNA repair, chromatin remodeling, programmed cell death, RNA regulation, and PAR-dependent ubiquitination. The advent of PARP inhibitors represents a new synthetic lethality paradigm for killing tumors bearing BRCA mutations in which tumor-specific defects are exploited to create a vulnerability that causes tumor cell death. To date, four PARP inhibitors have been approved by the US Food and Drug Administration for treatment of several types of cancer. In this review, we summarize the current knowledge of the molecular functions of PARP1 and highlight the recent advances in the use of PARP inhibitors in cancer treatment and the problem of drug resistance.

Breast cancer is the most common cancer type and ranks the second in cancer-related deaths in women. However, the relationship between inflammation-related gene signatures and the prognosis of breast cancer remains elusive. Here, we show that breast invasive carcinoma (BRCA) can be classified into high-risk and low-risk groups based on the level of inflammation. These groups have different tumor immune microenvironments, prognoses, and drug sensitivities. In general, breast cancer patients in high-risk groups have higher macrophage abundance, higher tumor mutation burden (TMB), and the signaling pathways related to the inflammatory response and immune response are activated. Our study demonstrates that the high-risk group of breast cancer patients exhibit a high prevalence of M2 macrophages, as well as a high incidence of tumor mutations in conjunction with an inflammatory response. Furthermore, our analysis indicates that PD.0332991 and ROSCOVITINE exhibit greater efficacy in the treatment of low-risk inflammatory breast cancer, while Bicalutamide and Imatinib demonstrate greater efficacy in the treatment of high-risk patients. In sum, our model exhibited numerous advantages. It not only overcame the challenge posed by the heterogeneity of cancer to clinical diagnosis, but also accurately predicted the prognosis of subtypes of breast cancer patients. This provides valuable reference for clinical practitioners and assists patients in obtaining the best chemotherapy regimen.

Long non-coding RNAs (lncRNA) are emerging as important players to keep genome stability and associate with human diseases including cancers (Statello et al., Statello et al., Nature Reviews Molecular Cell Biology 22:96–118, 2021). However, the underlying mechanisms that lncRNAs contribute to DNA damage response are not fully known. One of the limitations is that current studies depend on the physical interaction between lncRNA and the decoy, so that weak interactions might not be detected. Here we applied a method to label proximal lncRNAs of gH2ax, a marker of DNA damage, by antibody-mediated protein A-ascorbate peroxidase 2 (APEX2) and discovered that several lncRNA co-localized within DNA damage sites, including BGL3 which binds BARD1 and SNHG12 which interacts with DNA-PK (Haemmig et al., Haemmig et al., Sci Transl Med, 2020; Hu et al., Hu et al., EMBO Journal 39:e104133, 2020). In addition, we proved that knockdown of SNHG12 sensitized human cervical cancer HeLa and colon cancer HCT116 cells to irradiation. Overall, our study provides a new method to explore the function of lncRNA in DNA damage response.

Cancer is fundamentally a disturbance in the regulation of tissue development. Normal cells must undergo alterations in the genes responsible for cell proliferation and differentiation for cancer to arise. Carcinogenesis is the process through which cancer originates in healthy cells. It is characterized by cellular, genetic, and epigenetic alterations, as well as abnormal cell division. Oncogenes may be either normal genes with aberrant expression or mutant genes with surprising new abilities. Cancers are categorized with respect to the cell type involved in the cancerous growth. The categories include Carcinoma (Epithelial cells: lungs, breast, prostate, pancreas, intestine), Sarcoma (connective tissues: bone, cartilage, fat, nerves), Lymphoma & Leukaemia (immune system: lymph node & blood), Blastoma (embryonic cells), Germ cell tumour (ovarian & testicular germ cell). Cancer diagnosis involve an array of medical examinations such as blood count and X-ray imaging using electron endoscopy and computer-generated tomography. Tissue diagnosis reflects the histological grade, genetic abnormalities, and other properties of the proliferating cells which aid physicians in selecting the optimal course of treatment and determining the patient's prognosis. Cancer exhibits no visible symptoms except general symptoms such as unintended weight loss and fatigue. Chemotherapy refers to the use of one or more cytotoxic antineoplastic drugs (chemotherapeutic agents) in a specified treatment regime. It targets rapidly dividing cells, and its effectiveness is dependent on the type and severity of the disease. Classes of chemotherapeutic drugs are Alkylating agents, antimetabolites, Antitumor antibiotics, hormonal agents, plants alkaloids and miscellaneous agents. Other treatment of cancer includes the use of radiation, laser therapy, immunotherapy, and surgery. Cancer hotspots are areas of tumour DNA that are more susceptible to alteration. Examples of oncogenes with cancer hotspots include BRCA genes, p53 genes, APC genes, HER genes, PALB2 genes, ATM genes, ALK genes etc.