Genetic Variations Affect Chemotherapy Outcomes: A Role of the Spindle-assembly Checkpoint.

Cancer patients suffer from complicated chemotoxicity. Pharmacogenomics can help stratify patients by predicting their response to treatment and susceptibility toward severe side effects. The spindle-assembly checkpoint (SAC) is an important pathway that is activated by platinum and taxane compounds and plays a crucial role in their cytotoxic activity. This study investigated a SAC component, Budding Uninhibited by Benzimidazoles 3 (BUB3), its expression, and genetic variants in advanced ovarian cancer patients treated with paclitaxel-carboplatin chemotherapy. Among 80 patients, BUB3 expression correlated with chemosensitivity, suggesting its potential as a predictive marker for chemotherapy response. However, high BUB3 expression was associated with a higher risk of poor survival. In addition, genetic polymorphisms in BUB3 (rs11248416 and rs11248419) were significantly linked to chemotherapy-related toxicities, with rs11248416 showing a negative impact on the patient's physical quality of life.

Impact of Low BMI and Nutritional Status on Quality of Life and Disease Outcome in Breast Cancer Patients: Insights From a Tertiary Cancer Center in India.

This study investigates the impact of Body Mass Index (BMI) on Quality of Life (QoL) and treatment outcomes in breast cancer (BC) patients, particularly focusing on underweight individuals with compromised nutritional status. A nonrandomized prospective study comprising 121 newly diagnosed patients across various BMI categories utilized FACT-B & FACIT-Sp-12 questionnaires. Follow-ups occurred at baseline, during (3rd and 6th), and after (12th month) anthracycline-taxane chemotherapy, either sequentially or concomitantly. Patients with low BMI (<18.5 kg/m2; 53.7%) exhibited significantly poorer QoL, marked by compromised nutritional indicators (low MUAC and SFT). Repeated measures ANOVA identified significant correlations between BMI groups in functional, social, and emotional QoL aspects (p < 0.05), with no notable differences in other domains. A Chi-square (ꭓ2) test underscored a significant link between BMI and treatment response (p < 0.0001), showing higher rates of non-responders among underweight patients (p = 4.259e-14). The study advocates pretreatment consultation with a dietitian as standard care for Indian BC patients, offering complimentary nutritional support for improved QoL outcomes and treatment responses.

Bonobo Optimizer: A New Tool Toward the Global Optimization of Small Atomic Clusters.

In the realm of structural and bonding investigations within chemical systems, elucidating global minimum energy configurations stands as a paramount goal. As the systems increase in size and complexity, this pursuit becomes progressively challenging. Herein, we introduce Bonobo optimizer (BO), a metaheuristic algorithm inspired by the social and reproductive behaviors of bonobos, to the domain of chemical problem solving. Focusing on small carbon clusters, this study systematically evaluates BO's performance, showcasing its robustness and efficiency. Parametric studies highlight the algorithm's adaptability, consistently converging to global minimum structures. Rigorous statistical validation supports the results, and a comparative analysis against established global optimization algorithms underlines BO's superior efficiency. This exploration extends the applicability of BO to the optimization of atomic clusters, providing a promising avenue for future advancements in computational chemistry.

A signature of circulating miRNAs predicts the prognosis and therapeutic outcome of taxane/platinum regimen in advanced ovarian carcinoma patients.

PURPOSE: Ovarian carcinoma (OC) is ranked as the eighth most lethal gynecological cancer due to late diagnosis and high recurrence. Existing biomarkers are lacking to predict the recurrence and stratify patients who are likely to benefit from chemotherapy. MicroRNAs (miRNAs/miRs) are persistently present in humans and are capable of predicting treatment outcomes. Thus, the purpose of the study was to assess the potential of circulatory miRNAs to predict the efficacy of OC. METHODS: Newly diagnosed n = 208 OC patients were administrated neoadjuvant/adjuvant chemotherapy (taxane + platinum) after surgery. Their demographic, gynecologic, clinical parameters, response, and survival were recorded. MiR-27a, miR-182, miR-199a, miR-214, and miR-591 were taken and the expression were analyzed using real-time PCR at different treatment intervals. Further, its prognostic value (Kaplan-Meier, and Cox regression analysis) and diagnostic importance (receiver operating characteristic curve) were validated. RESULT: The mean age of patients with poorly differentiated (45.2%) serous OC was 48.69 ± 10.38. The majority experienced menarche at ≥ 12 (62.2%) with poor menstrual hygiene (81.8%) and were post-menopausal (69.4%), some were associated with high risk of survival (HR = > 1). MiRNA signature showed three over-expression and two under-expression (miR-27a, miR-182, and miR-214; miR-199a and miR-591) in advanced OC compared to the control (P= < 0.05). Also, a significant difference was detected at each time interval of treatment with the response (P = ≤ 0.001) associated with resistance and overall survival (P = ≤ 0.001) with risk (HR = > 1). ROC analysis showed enhanced the diagnostics accuracy (< 0.001). CONCLUSION: Our findings indicate that circulating miRNAs might be a potential minimally invasive diagnostic marker for treatment outcome and recurrence in ovarian carcinoma.

Potential role of immune cell therapy in gynecological cancer and future promises: a comprehensive review.

Gynecological malignancies are most leading causes of death among women worldwide. The high prevalence of gynecologic malignancies remains significant, necessitating to turn the novel treatment approach like immunotherapy, wherein cancer cells are killed by the invasion of immune system. In recent year, immunotherapy has mostly an advanced treatment approach to repressing the tumor cells survival, proliferation, and invasion via the activation of immune systems. Moreover, various types of immune cells including T-cells, B-cells, and dendritic cells are associated with the immunotherapeutic strategy in cancer treatment. Although the significant role of T-cells against cancer is well established, while B-cells and dendritic cells also play an important role against different gynecological cancer by regulating the immune system. This review focuses on that arena and highlight the role of immune cells in the treatment of gynaecological cancer. Various immune cell-based anticancer therapies such as T-cell therapies, Adoptive Cellular transfer, B-cell therapies as well as approaches to Dendritic Cell therapies have been discussed in detail. Furthermore, the clinical settings and future avenues regarding immunotherapy on gynecological cancer have also been reviewed and illuminated in the recent study.

Structure, stability, reactivity and bonding in noble gas compounds.

Noble gases (Ngs) are recognized as the least reactive elements due to their fully filled valence electronic configuration. Their reluctance to engage in chemical bond formation necessitates extreme conditions such as low temperatures, high pressures, and reagents with high reactivity. In this Perspective, we discuss our endeavours in the theoretical prediction of viable Ng complexes, emphasizing the pursuit of synthesizing them under nearly ambient conditions. Our research encompasses various bonding categories of Ng complexes and our primary aim is to comprehend the bonding mechanisms within these complexes, utilizing state-of-the-art theoretical tools such as natural bond orbital, energy decomposition, and electron density analyses. These complex types manifest distinct bonding scenarios. In the non-insertion type, the donor-acceptor interaction strength hinges on the polarizing ability of the binding atom, drawing the electron density of the Ng towards itself. In certain instances, especially with heavier Ng elements, this interaction reaches a magnitude where it can be considered a covalent bond. Conversely, in most insertion cases, the Ng prefers to share electrons to form a covalent bond on one side while interacting electrostatically on the other side. In rare cases, both bonds may be portrayed as electron-shared covalent bonds. Furthermore, a host cage serves as an excellent platform to explore the limits of achieving Ng-Ng bonds (even for helium), under high pressure.

Outcomes of 3-year follow up with induction vs first line chemotherapy in oral cancer patients: An observational hospital-based study.

OBJECTIVE: Our study aims to analyse and compare the efficacy, adverse effect profile and survival among the Paclitaxel/Cisplatin/5-Flurouracil (TPF) induction chemotherapy and Paclitaxel/carboplatin (PC) first line or cisplatin chemotherapy in a high-volume tertiary care cancer centre. MATERIALS AND METHODS: 215 patients with oral cavity cancer were recruited in this study. Patients with stages I-IIc underwent surgical resection or radiation therapy 66-74 GY/fraction. Patients of Stages III-IV were administered with either induction chemotherapy TPF or PC or cisplatin regimen. Treatment responses were assessed by CT and MRI. Response rates, survival and adverse effects data were tabulated and analysed. RESULTS: The mean age was 49.2 ± 11.68 years. Symptoms were ulceration (33.5%), growth (20.5%), pain (13%), ulcer-proliferative growth (8.4%) and swelling (13, 6%). The tumour site was found at the base of the tongue, C01 (42.2%) followed by C06 (35.8%), C08 (6.5%), C07 (5.2%) and C05 (4.6%). There were no significant differences (P > 0.05) in efficacy and survival outcomes between the different groups of treatment. Median survival was achieved within 36 months. The major side effect observed were anaemia (15.81%), diarrhoea (36.2%), dyspepsia (28.8%), fever (33.95%), mucositis (28.85%), myalgia (33.95%) and nausea (7.9%). Survival among the responder categories (CR, PR and NR) was significantly different as per Log-rank analysis (P = 0.015). CONCLUSIONS: TPF induction therapy and PC first line chemotherapy showed similar efficacy, safety profile and survival whereas cisplatin shows poor efficacy and safety and survival in Indian oral cancer patients.

Emerging Futuristic Targeted Therapeutics: A Comprising Study Towards a New Era for the Management of TNBC.

Triple-negative breast cancer is characterized by high lethality attributed to factors such as chemoresistance, transcriptomic, and genomic heterogeneity, leading to a poor prognosis and limiting available targeted treatment options. While the identification of molecular targets remains pivotal for therapy involving chemo drugs, the current challenge lies in the poor response rates, low survival rates, and frequent relapses. Despite various clinical investigations exploring molecular targeted therapies in conjunction with conventional chemo treatment, the outcomes have been less than optimal. The critical need for more effective therapies underscores the urgency to discover potent novel treatments, including molecular and immune targets, as well as emerging strategies. This review provides a comprehensive analysis of conventional treatment approaches and explores emerging molecular and immune-targeted therapeutics, elucidating their mechanisms to address the existing obstacles for a more effective management of triple-negative breast cancer.

Frustrated Lewis Pairs: Bonding, Reactivity, and Applications.

The outstanding capability of Frustrated Lewis Pair (FLP) catalysts to activate small molecules has gained significant attention in recent times. Reactivity of FLP is further extended toward the hydrogenation of various unsaturated species. Over the past decade, this unique catalysis concept has been successfully expanded to heterogeneous catalysis as well. The present review article gives a brief survey on several studies on this field. A thorough discussion on quantum chemical studies concerning the activation of H2 is provided. The role of aromaticity and boron-ligand cooperation on the reactivity of FLP is discussed in the Review. How FLP can activate other small molecules by cooperative action of its Lewis centers is also discussed. Further, the discussion is shifted to the hydrogenation of various unsaturated species and the mechanism regarding this process. It also discusses the latest theoretical advancements in the application of FLP in heterogeneous catalysis across various domains, such as two-dimensional materials, functionalized surfaces, and metal oxides. A deeper understanding of the catalytic process may assist in devising new heterogeneous FLP catalysts through experimental design.

On the Nature of the Partial Covalent Bond between Noble Gas Elements and Noble Metal Atoms.

This article provides a discussion on the nature of bonding between noble gases (Ng) and noble metals (M) from a quantum chemical perspective by investigating compounds such as NgMY (Y=CN, O, NO3, SO4, CO3), [NgM-(bipy)]+, NgMCCH, and MCCNgH complexes, where M=Cu, Ag, Au and Ng=Kr-Rn, with some complexes containing the lighter noble gas atoms as well. Despite having very low chemical reactivity, noble gases have been observed to form weak bonds with noble metals such as copper, gold, and silver. In this study, we explore the factors that contribute to this unusual bonding behavior, including the electronic structure of the atoms involved and the geometric configuration of the concerned fragments. We also investigate the metastable nature of the resulting complexes by studying the energetics of their possible dissociation and internal isomerization channels. The noble gas-binding ability of the bare metal cyanides are higher than most of their bromide counterparts, with CuCN and AgCN showing higher affinity than their chloride analogues as well. In contrast, the oxides seem to have lower binding power than their corresponding halides. In the oxide and the bipyridyl complexes, the Ng-binding ability follows the order Au > Cu > Ag. The dissociation energies calculated, considering the zero-point energy correction for possible dissociation channels, increase as we move down the noble gas group. The bond between the noble gases and the noble metals in the complexes are found to have comparable weightage of orbital and electrostatic interactions, suggestive of a partial covalent nature. The same is validated from the topological analysis of electron density.

Global Optimization: A Soft Computing Perspective.

Tackling the problem of global optimization is one of the most important domains that physicists and chemists are working on. The use of soft computing (SC) techniques has made this easier by reducing nonlinearity and instability and making it technologically rich. This Perspective aims at explaining the basic mathematical models of the most efficient and commonly used SC techniques in computational chemistry for finding the global minimum (GM) energy structures of chemical systems. In this Perspective, we discuss the global optimizations of several chemical systems that our group has worked on using CNN, PSO, FA, ABC, BO, and some hybrid techniques, two of which are interfaced to achieve better-quality results.

Electrophilicity index revisited.

This review aims to be a comprehensive, authoritative, critical, and accessible review of general interest to the chemistry community; because the electrophilicity index is a very useful global reactivity descriptor defined within a conceptual density functional theory framework. Our group has also introduced electrophilicity based new global and local reactivity descriptors and also new associated electronic structure principles, which are important indicators of structure, stability, bonding, reactivity, interactions, and dynamics in a wide variety of physico-chemical systems and processes. This index along with its local counterpart augmented by the associated electronic structure principles could properly explain molecular vibrations, internal rotations and various types of chemical reactions. The concept of the electrophilicity index has been extended to dynamical processes, excited states, confined environment, spin-dependent and temperature-dependent situations, biological activity, site selectivity, aromaticity, charge removal and acceptance, presence of external perturbation through solvents, external electric and magnetic fields, and so forth. Although electrophilicity and its local variant can adequately interpret the behavior of a wide variety of systems and different physico-chemical processes involving them, their predictive potential remains to be explored. An exhaustive review on all these aspects will set the tone of the future research in that direction.

Can the Fluxionality in Borospherene Influence the Confinement-Induced Bonding between Two Noble Gas Atoms?

A density functional theory study is performed to determine the stability and bonding in the neon dimer inside the B30N30 fullerene cage, the fluxional B40 cage, and within non-fluxional cages such as B12N12 and C60. The nature of bonding in the Ne2 encapsulated B40 is compared with the that in other cages in an attempt to determine whether any possible alterations are brought about by the dynamical nature of the host cage apart from the associated confinement effects. The bonding analysis includes the natural bond order (NBO), Bader's Atoms-in-Molecules electron density analysis (AIM), and energy decomposition analysis (EDA), revealing the non-covalent nature of the interactions between the Ne atoms and that between the Ne and the cage atoms. The formation of all the Ne2@cage systems is thermochemically unfavourable, the least being that for the B30N30 cage, which can easily be made favourable at lower temperatures. The Ne-Ne distance is lowest in the smallest cage and increases as the cage size increase due to steric relaxation experienced by the dimer. The dynamical picture of the systems is investigated by performing ab initio molecular dynamics simulations using the atom-centred density matrix propagation (ADMP) technique, which shows the nature of the movement of the dimer inside the cages, and by the fact that since it moves as a single entity, a weak bonding force holds them together, apart from their proven kinetic stability.

Quantitative Structure-Toxicity Relationship in Bioactive Molecules from a Conceptual DFT Perspective.

The preclinical drug discovery stage often requires a large amount of costly and time-consuming experiments using huge sets of chemical compounds. In the last few decades, this process has undergone significant improvements by the introduction of quantitative structure-activity relationship (QSAR) modelling that uses a certain percentage of experimental data to predict the biological activity/property of compounds with similar structural skeleton and/or containing a particular functional group(s). The use of machine learning tools along with it has made life even easier for pharmaceutical researchers. Here, we discuss the toxicity of certain sets of bioactive compounds towards Pimephales promelas and Tetrahymena pyriformis in terms of the global conceptual density functional theory (CDFT)-based descriptor, electrophilicity index (ω). We have compared the results with those obtained by using the commonly used hydrophobicity parameter, logP (where P is the n-octanol/water partition coefficient), considering the greater ease of computing the ω descriptor. The Human African trypanosomiasis (HAT) curing activity of 32 pyridyl benzamide derivatives is also studied against Tryphanosoma brucei. In this review article, we summarize these multiple linear regression (MLR)-based QSAR studies in terms of electrophilicity (ω, ω2) and hydrophobicity (logP, (logP)2) parameters.

On the Periodicity of the Information Theory and Conceptual DFT-Based Reactivity Descriptors.

The periodic trends in conceptual density functional and information theory-based reactivity descriptors are reported for the atoms H to Ba (Z = 1 to 56). Ionization potential, electron affinity, electronegativity, and hardness show periodic behavior following the Aufbau principle and popular electronic structure principles. They are in agreement with those reported in standard chemistry textbooks. The trend in the electrophilicity index, however, shows an interesting behavior, where it contradicts earlier reports. Our calculation reveals that the noble gas elements correspond to minimum ω values in each period which obey the minimum electrophilicity principle as well as reflect their low reactivity. Periodic trends in electroaccepting and electrodonating powers, along with that of net electrophilicity, are as expected. The behavior of information theory-based Shannon and GBP entropies, along with the Shannon entropy of shape function are also explored across the periodic table.

PIM1/STAT3 axis: a potential co-targeted therapeutic approach in triple-negative breast cancer.

Triple-negative breast cancer lacks an expression of ER, PR, and Her-2, has a poor prognosis, and there are no target therapies available. Therapeutic options to treat TNBC are limited and urgently needed. Strong evidence indicates that molecular signaling pathways have a significant function to regulate biological mechanisms and their abnormal expression endows with the development of cancer. PIM kinase is overexpressed in various human cancers including TNBC which is regulated by various signaling pathways that are crucial for cancer cell proliferation and survival and also make PIM kinase as an attractive drug target. One of the targets of the STAT3 signaling pathway is PIM1 that plays a key role in tumor progression and transformation. In this review, we accumulate the current scenario of the PIM-STAT3 axis that provides insights into the PIM1 and STAT3 inhibitors which can be developed as potential co-inhibitors as prospective anticancer agents.

Evaluation of numerical rating scale and neuropathic pain symptom inventory pain scores in advanced ovarian carcinoma patients undergoing surgery and first-line chemotherapy.

BACKGROUND AND AIM: Advanced epithelial ovarian cancer (OC) has a high disease manifestation with difficult-to-manage symptoms that limit the patients' functionality. Abdominal pain, persistent back pain, and neuropathic pain are among the common discomforts associated with OC and its treatment. Our study aims to determine pain scores in advanced OC patients undergoing surgery and chemotherapeutic treatment with carboplatin and paclitaxel. METHODS: One hundred and ten patients with advanced epithelial OC were enrolled and treated with surgery and an adjuvant/neoadjuvant chemotherapy regimen of carboplatin-paclitaxel for six cycles (triweekly). Pain intensity was analyzed using the validated numerical rating scale for resting, movement, sleep interference-associated pain, and neuropathic pain scores were evaluated using the neuropathic pain symptom inventory scale. Pain was correlated with Qol according to Fact-O questionnaires. Chemo-response was evaluated using the CA125 blood biomarker and CT scan of the abdomen and thorax. Data were recorded at baseline, 2, 4, and 6 months of the six chemotherapy cycles. RESULTS: Of the 110 patients, no statistically significant differences were found in pain at baseline and after treatment (P > 0.05) and between the responder and non-responder categories (P > 0.05). However, movement-associated pain had a significant correlation with chemo-response and a strong positive correlation with the patients' physical and functional wellbeing. There were more chemo-induced neuropathy occurrences (P = 0.001) in the neoadjuvant chemotherapy group. CONCLUSION: Patients in the neoadjuvant chemotherapy arm experienced more chemo-induced neuropathy that was persistent and did not improve with the treatment. RELEVANCE FOR PATIENTS: Peripheral neuropathy is a common adverse effect of platinum and taxane chemotherapeutic drugs that persists throughout cancer treatment and in survivorship. This research provides evidence that chemotherapy-associated neuropathy affects Qol of patients and it will be helpful to improve pain and palliative care management policies.

Assessment of quality of life among advanced ovarian cancer patients in a tertiary care hospital in India.

PURPOSE: The study aims to record the quality of life (Qol) and its changes while ovarian cancer (OC) patients undergo debulking surgeries and chemotherapy in a tertiary care hospital of Eastern India. METHODS: Patients with advanced epithelial OC (FIGO stages III-IV) were recruited. They underwent primary/interval debulking surgeries with classical chemotherapy (adjuvant/neoadjuvant) of intravenous tri-weekly doses of paclitaxel + carboplatin. QoL was assessed using Fact- O + FACIT-Sp-12 questionnaire with a set of 51 questions in different domains (spiritual, physical, social, emotional, and functional factors) and a special set for OC patients under the heading "Additional concerns." The responses from patients were recorded at baseline (diagnosis/study entry), 2, 4, and 6 months during the treatment visits. Overall survival (OS) was assessed using Kaplan Meier curve. RESULTS: A majority of patients were 49.15±10.8 years of age, school-educated (54%), unemployed/homemakers (73.5%), belonging from rural setup (64.6%) with a monthly income of Rs. 2000/- to Rs. 5000/-. There was no statistically significant (p>0.05) improvement found in Qol from the baseline till the end of the study, neither overall nor in subsets (responders (Rs)/partial responders (PRs)/non-responder (NRs) groups or the adjuvant and neoadjuvant chemotherapy groups). The common toxicities like anemia, constipation, and weight loss were significantly (p<0.05) correlated with the patients' physical, functional, emotional, and social well-being. CONCLUSION: Ovarian cancer patients represent a poor functional, social, and disease-specific quality of life that needs to be addressed, identified, and improved by the growing nexus of healthcare providers and researchers.

XNgNSi (X = HCC, F; Ng = Kr, Xe, Rn): A New Class of Metastable Insertion Compounds Containing Ng-C/F and Ng-N Bonds and Possible Isomerization therein.

Recently, astronomically important silaisocyanoacetylene (HCCNSi) possessing a large dipole moment has been detected for the first time with the help of crossed molecular beam experiments. Quantum chemical computations at higher levels of theory have also been performed to characterize the transient species. In this study, we have analyzed the equilibrium geometry, stability, reactivity, and energetics as well as the nature of bonding in the noble gas (Ng) inserted HCCNSi compound. We have also considered its F analogue to understand the influence of the most electronegative atom in the compound. Metastable behavior of the XNgNSi compounds (X = HCC, F; Ng = Kr-Rn) is examined by calculating thermochemical parameters like free energy change (ΔG) and zero-point-energy-corrected dissociation energy (D0) at 298 K for all possible two-body (2B) and three-body (3B) (both neutral as well as ionic) dissociation channels using coupled-cluster theory [CCSD(T)] in addition to density functional theory (DFT) as well as second order Møller-Plesset perturbation theory (MP2). The set of predicted compounds is found to be endergonic in nature, having high positive free energy change suggesting the thermochemical stability of the compounds except for the 2B Ng-release paths. Though thermodynamically feasible, they are kinetically protected with very high activation free energy barriers. Interestingly, the release of Ng from the parent moiety XNgNSi produces the XSiN isomer, by 180° flipping of the NSi moiety. This can also be seen in the dynamical simulation carried out with the help of atom-centered density matrix propagation (ADMP) technique at 2000K for 1 ps. The bonding in Ng-C, Ng-F, and Ng-N bonds of the studied compounds is analyzed and described with the aid of natural bond orbital (NBO), topological parameters computed using atoms-in-molecules theory (AIM), energy decomposition analysis (EDA), and adaptive natural density partitioning (AdNDP) methods. The natural charge distribution on the constituent atoms suggests that the compounds can be partitioned into both ways of representations, viz., neutral radical as well as ionic fragments. Lastly, the reactivity of the compounds is scrutinized using certain reactivity descriptors calculated within the domain of conceptual density functional theory (CDFT).

Molecular targets and therapeutics in chemoresistance of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer (BC), which shows immunohistochemically negative expression of hormone receptor i.e., Estrogen receptor and Progesterone receptor along with the absence of Human Epidermal Growth Factor Receptor-2 (HER2/neu). In Indian scenario the prevalence of BC is 26.3%, whereas, in West Bengal the cases are of 18.4%. But the rate of TNBC has increased up to 31% and shows 27% of total BC. Conventional chemotherapy is effective only in the initial stages but with progression of the disease the effectivity gets reduced and shown almost no effect in later or advanced stages of TNBC. Thus, TNBC patients frequently develop resistance and metastasis, due to its peculiar triple-negative nature most of the hormonal therapies also fails. Development of chemoresistance may involve various factors, such as, TNBC heterogeneity, cancer stem cells (CSCs), signaling pathway deregulation, DNA repair mechanism, hypoxia, and other molecular factors. To overcome the challenges to treat TNBC various targets and molecules have been exploited including CSCs modulator, drug efflux transporters, hypoxic factors, apoptotic proteins, and regulatory signaling pathways. Moreover, to improve the targets and efficacy of treatments researchers are emphasizing on targeted therapy for TNBC. In this review, an effort has been made to focus on phenotypic and molecular variations in TNBC along with the role of conventional as well as newly identified pathways and strategies to overcome challenge of chemoresistance.