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<p>Cancer remains a significant medical crisis and health burden globally, with an estimated 20 million new cases and nearly 10 million deaths annually, as per GLOBOCAN 2022. The disease burden continues to grow due to an ageing population, changes in lifestyle, environmental exposure and enhanced cancer detection, leading to enormous pressure on healthcare systems and requiring ongoing research to develop novel treatment modalities. Tumor growth maintains a sigmoidal pattern ruled by tumor growth kinetics (TGK), with the logarithmic phase characterized by rapid proliferation, high growth fraction and increased therapeutic vulnerability. Intratumoral heterogeneity frequently obscures even therapeutic responses, making this phase a critical yet complex target for therapeutic interventions. This review explores evidence on exploiting the logarithmic phase to augment cancer treatment outcomes, combining traditional anticancer therapies along with natural compounds as adjuncts, and emerging biomarkers, while addressing heterogeneity-driven drug resistance. We analyzed TGK models and phase-specific vulnerabilities, highlighting efficacy of chemotherapy (cisplatin, paclitaxel, 5-FU), targeted agents (osimertinib, inavolisib), hormonal therapies (fulvestrant) and immunotherapies (pembrolizumab, durvalumab) across breast, lung, prostate, colorectal cancers, leukemias and lymphomas. Cancer heterogeneity, such as subclonal diversity, variable proliferative states and microenvironmental niches required combination and adaptive strategies to overcome resistance. Natural compounds (curcumin, resveratrol, EGCG, quercetin, genistein) have demonstrated preclinical efficacy by inhibiting proliferation, modulating resistance pathways (NF-κB, STAT3), enhancing chemosensitivity and modifying drug toxicities. These strategies are supported by the recent clinical trial evidence highlighting excellent tolerability and adjunctive benefits. Real-time monitoring using Ki-67, circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs) enables dynamic evaluation of kinetics and heterogeneity shifts. Targeting the logarithmic phase, while accounting for tumor heterogeneity through multimodal, adaptive and biomarker-guided approaches combined with natural products, offers a hopeful precision oncology strategy. This strategy holds strong potential to interrupt resistance, increase survival and transform aggressive cancers into manageable chronic conditions, leading to a better quality of life.</p>

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The logarithmic phase as a therapeutic direction: evaluating pharmacological strategies against cancer progression

  • 期刊论文

  • 发表日期：

    2026年3月28日

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  • Sushanta Kumar Das,
  • Saptarshi Dutta,
  • Sabitri Pradhan,
  • Rintu Saikia

摘要

Cancer remains a significant medical crisis and health burden globally, with an estimated 20 million new cases and nearly 10 million deaths annually, as per GLOBOCAN 2022. The disease burden continues to grow due to an ageing population, changes in lifestyle, environmental exposure and enhanced cancer detection, leading to enormous pressure on healthcare systems and requiring ongoing research to develop novel treatment modalities. Tumor growth maintains a sigmoidal pattern ruled by tumor growth kinetics (TGK), with the logarithmic phase characterized by rapid proliferation, high growth fraction and increased therapeutic vulnerability. Intratumoral heterogeneity frequently obscures even therapeutic responses, making this phase a critical yet complex target for therapeutic interventions. This review explores evidence on exploiting the logarithmic phase to augment cancer treatment outcomes, combining traditional anticancer therapies along with natural compounds as adjuncts, and emerging biomarkers, while addressing heterogeneity-driven drug resistance. We analyzed TGK models and phase-specific vulnerabilities, highlighting efficacy of chemotherapy (cisplatin, paclitaxel, 5-FU), targeted agents (osimertinib, inavolisib), hormonal therapies (fulvestrant) and immunotherapies (pembrolizumab, durvalumab) across breast, lung, prostate, colorectal cancers, leukemias and lymphomas. Cancer heterogeneity, such as subclonal diversity, variable proliferative states and microenvironmental niches required combination and adaptive strategies to overcome resistance. Natural compounds (curcumin, resveratrol, EGCG, quercetin, genistein) have demonstrated preclinical efficacy by inhibiting proliferation, modulating resistance pathways (NF-κB, STAT3), enhancing chemosensitivity and modifying drug toxicities. These strategies are supported by the recent clinical trial evidence highlighting excellent tolerability and adjunctive benefits. Real-time monitoring using Ki-67, circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs) enables dynamic evaluation of kinetics and heterogeneity shifts. Targeting the logarithmic phase, while accounting for tumor heterogeneity through multimodal, adaptive and biomarker-guided approaches combined with natural products, offers a hopeful precision oncology strategy. This strategy holds strong potential to interrupt resistance, increase survival and transform aggressive cancers into manageable chronic conditions, leading to a better quality of life.