First clinical evaluation of a phosphoinositide 3-kinase (PI3K) inhibitor for the treatment of advanced prostate cancer.

癌症治疗的未来进展取决于我们将癌症生物学知识转化为新的治疗方法，以提供个性化的患者治疗。实验室研究正在迅速确定调节细胞行为的关键基因或分子开关的特征，从而可以确定这些开关中导致细胞失控和癌症生长的缺陷。包括前列腺癌、卵巢癌、乳腺癌、结肠直肠癌、脑癌和儿童癌在内的大量人类癌症的共同特征是称为PI 3 K途径的关键细胞途径的分子开关缺陷。这种途径的失控在前列腺癌中非常常见。英国癌症研究所癌症治疗中心的研究人员与Pagummed的同事合作，开发了专门针对PI 3 K的合理设计的药物。这些药物在实验室中阻止肿瘤生长，并且由于其高选择性，具有吸引人的副作用，与癌症化疗不同，避免了患者不必要的不良反应。由于有压倒性的实验室证据支持开发针对这一途径的抗癌药物，特别是在前列腺癌患者中，我们现在提议在所有已知抗癌治疗失败的晚期癌症患者中进行PDP-101620的首次临床试验，PDP-101620是针对这一关键开关开发的药物。这项临床试验将首先评估PDP 101620是否可以安全地阻止PI 3 K的功能，PI 3 K是专门设计用于阻断的关键分子开关。一旦成功完成，将利用复杂的分子测试和癌症成像来确定导致最大抗癌效果的最佳剂量和给药频率。这将导致在晚期前列腺癌患者中评估PDP-101620对PI 3 K的阻断作用，这些患者的癌症已经扩散到前列腺外并且标准治疗失败。将确定这种靶向调节对晚期前列腺癌生长的影响。据设想，用PDP-101620治疗将抑制许多但不是所有患有这种疾病的患者的前列腺癌生长，通过延长生存期和改善生活质量以及有利的副作用特征而使患者受益。这些研究将支持前瞻性识别可能从PDP 101620中获益的患者。

Future advances in the treatment of cancer depend on the translation of our knowledge of cancer biology to novel treatments in order to deliver individualised patient treatment. Laboratory research is rapidly characterising the key genes, or molecular switches, that regulate cellular behaviour, allowing the identification of the defects in these switches that result in the loss of cell control and cancer growth. A common feature of a large number of human cancers including prostate, ovarian, breast, colorectal, brain and childhood cancers is defective molecular switches of a key cellular pathway called the PI3K pathway. Loss of control of this pathway is very common in prostate cancer. Researchers at the Cancer Research UK Centre for Cancer Therapeutics, at the Institute of Cancer Research, have developed rationally designed drugs specifically targeting PI3K, in collaboration with colleagues at PIramed. These drugs stop tumour growth in the laboratory, and due to their high selectivity have an attractive side-effects profile, unlike cancer chemotherapy, sparing the patient unwanted adverse effects. Since there is overwhelming laboratory evidence supporting the development of anticancer drugs against this pathway, particularly in prostate cancer patients, we now propose the first clinical trials of PDP-101620, a drug developed against this key switch, in consenting patients with advanced cancer who have failed all known anticancer treatments. This clinical trial will first evaluate whether PDP101620 can safely prevent the function of PI3K, the critical molecular switch it was specifically designed to block. Once this is successfully completed, the optimal dose and administration frequency resulting in maximal anticancer effect will be determined utilising sophisticated molecular testing and cancer imaging. This will then lead to the evaluation of PI3K blockade by PDP-101620 in patients with advanced prostate cancer, whose cancer has spread outside the prostate and failed standard treatment. The effect that this target modulation has on advanced prostate cancer growth will be determined. It is envisioned that treatment with PDP-101620 will inhibit prostate cancer growth in many but not all patients with this disease, resulting in patient benefit by prolonging survival and improving quality of life with a favourable side-effect profile. These studies will support the prospective identification of patients likely to benefit from PDP101620.